Nerve Impulse
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An action potential occurs when the membrane potential of a specific
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
location rapidly rises and falls. This
depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is ess ...
then causes adjacent locations to similarly depolarize. Action potentials occur in several types of
animal cell Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacter ...
s, called excitable cells, which include
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s,
muscle cells A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a mus ...
, and in some plant cells. Certain endocrine cells such as
pancreatic beta cell Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dimin ...
s, and certain cells of the
anterior pituitary gland A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...
are also excitable cells. In neurons, action potentials play a central role in
cell-cell communication In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
by providing for—or with regard to
saltatory conduction In neuroscience, saltatory conduction () is the propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials. The uninsulated nodes of Ranvier are th ...
, assisting—the propagation of signals along the neuron's
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...
toward synaptic boutons situated at the ends of an axon; these signals can then connect with other neurons at synapses, or to motor cells or glands. In other types of cells, their main function is to activate intracellular processes. In muscle cells, for example, an action potential is the first step in the chain of events leading to contraction. In
beta cell Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dimini ...
s of the
pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...
, they provoke release of
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
. Action potentials in neurons are also known as "nerve impulses" or "spikes", and the temporal sequence of action potentials generated by a neuron is called its "spike train". A neuron that emits an action potential, or nerve impulse, is often said to "fire". Action potentials are generated by special types of
voltage-gated ion channel Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, ...
s embedded in a cell's plasma membrane. These channels are shut when the membrane potential is near the (negative)
resting potential A relatively static membrane potential which is usually referred to as the ground value for trans-membrane voltage. The relatively static membrane potential of quiescent cells is called the resting membrane potential (or resting voltage), as opp ...
of the cell, but they rapidly begin to open if the membrane potential increases to a precisely defined threshold voltage, depolarising the transmembrane potential. When the channels open, they allow an inward flow of
sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
ions, which changes the electrochemical gradient, which in turn produces a further rise in the membrane potential towards zero. This then causes more channels to open, producing a greater electric current across the cell membrane and so on. The process proceeds explosively until all of the available ion channels are open, resulting in a large upswing in the membrane potential. The rapid influx of sodium ions causes the polarity of the plasma membrane to reverse, and the ion channels then rapidly inactivate. As the
sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
s close, sodium ions can no longer enter the neuron, and they are then actively transported back out of the plasma membrane.
Potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
channels are then activated, and there is an outward current of potassium ions, returning the electrochemical gradient to the resting state. After an action potential has occurred, there is a transient negative shift, called the
afterhyperpolarization Afterhyperpolarization, or AHP, is the hyperpolarizing phase of a neuron's action potential where the cell's membrane potential falls below the normal resting potential. This is also commonly referred to as an action potential's undershoot phas ...
. In animal cells, there are two primary types of action potentials. One type is generated by
voltage-gated sodium channels Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
, the other by
voltage-gated calcium channel Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeabili ...
s. Sodium-based action potentials usually last for under one millisecond, but calcium-based action potentials may last for 100 milliseconds or longer. In some types of neurons, slow calcium spikes provide the driving force for a long burst of rapidly emitted sodium spikes. In
cardiac muscle cells Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...
, on the other hand, an initial fast sodium spike provides a "primer" to provoke the rapid onset of a calcium spike, which then produces muscle contraction.


Overview

Nearly all
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
s in animals, plants and fungi maintain a
voltage Voltage, also known as electric pressure, electric tension, or (electric) potential difference, is the difference in electric potential between two points. In a static electric field, it corresponds to the work needed per unit of charge to m ...
difference between the exterior and interior of the cell, called the membrane potential. A typical voltage across an animal cell membrane is −70 mV. This means that the interior of the cell has a negative voltage relative to the exterior. In most types of cells, the membrane potential usually stays fairly constant. Some types of cells, however, are electrically active in the sense that their voltages fluctuate over time. In some types of electrically active cells, including
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s and muscle cells, the voltage fluctuations frequently take the form of a rapid upward (positive) spike followed by a rapid fall. These up-and-down cycles are known as ''action potentials''. In some types of neurons, the entire up-and-down cycle takes place in a few thousandths of a second. In muscle cells, a typical action potential lasts about a fifth of a second. In plant cells, an action potential may last three seconds or more. The electrical properties of a cell are determined by the structure of its membrane. A
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
consists of a
lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
of molecules in which larger protein molecules are embedded. The lipid bilayer is highly resistant to movement of electrically charged ions, so it functions as an insulator. The large membrane-embedded proteins, in contrast, provide channels through which ions can pass across the membrane. Action potentials are driven by channel proteins whose configuration switches between closed and open states as a function of the voltage difference between the interior and exterior of the cell. These voltage-sensitive proteins are known as
voltage-gated ion channel Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, ...
s.


Process in a typical neuron

All cells in animal body tissues are electrically polarized – in other words, they maintain a voltage difference across the cell's plasma membrane, known as the membrane potential. This electrical polarization results from a complex interplay between protein structures embedded in the membrane called
ion pump An ion pump (also referred to as a sputter ion pump) is a type of vacuum pump which operates by sputtering a metal getter. Under ideal conditions, ion pumps are capable of reaching pressures as low as 10−11 mbar. An ion pump first ionizes ga ...
s and
ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
s. In neurons, the types of ion channels in the membrane usually vary across different parts of the cell, giving the
dendrite Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the ...
s,
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...
, and cell body different electrical properties. As a result, some parts of the membrane of a neuron may be excitable (capable of generating action potentials), whereas others are not. Recent studies have shown that the most excitable part of a neuron is the part after the
axon hillock The axon hillock is a specialized part of the cell body (or soma) of a neuron that connects to the axon. It can be identified using light microscopy from its appearance and location in a neuron and from its sparse distribution of Nissl substance. ...
(the point where the axon leaves the cell body), which is called the
axonal initial segment An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...
, but the axon and cell body are also excitable in most cases. Each excitable patch of membrane has two important levels of membrane potential: the
resting potential A relatively static membrane potential which is usually referred to as the ground value for trans-membrane voltage. The relatively static membrane potential of quiescent cells is called the resting membrane potential (or resting voltage), as opp ...
, which is the value the membrane potential maintains as long as nothing perturbs the cell, and a higher value called the
threshold potential In electrophysiology, the threshold potential is the critical level to which a membrane potential must be depolarized to initiate an action potential. In neuroscience, threshold potentials are necessary to regulate and propagate signaling in both ...
. At the axon hillock of a typical neuron, the resting potential is around –70 millivolts (mV) and the threshold potential is around –55 mV. Synaptic inputs to a neuron cause the membrane to depolarize or hyperpolarize; that is, they cause the membrane potential to rise or fall. Action potentials are triggered when enough depolarization accumulates to bring the membrane potential up to threshold. When an action potential is triggered, the membrane potential abruptly shoots upward and then equally abruptly shoots back downward, often ending below the resting level, where it remains for some period of time. The shape of the action potential is stereotyped; this means that the rise and fall usually have approximately the same amplitude and time course for all action potentials in a given cell. (Exceptions are discussed later in the article). In most neurons, the entire process takes place in about a thousandth of a second. Many types of neurons emit action potentials constantly at rates of up to 10–100 per second. However, some types are much quieter, and may go for minutes or longer without emitting any action potentials.


Biophysical basis

Action potentials result from the presence in a cell's membrane of special types of
voltage-gated ion channel Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, ...
s. A voltage-gated ion channel is a transmembrane protein that has three key properties: #It is capable of assuming more than one conformation. #At least one of the conformations creates a channel through the membrane that is permeable to specific types of ions. #The transition between conformations is influenced by the membrane potential. Thus, a voltage-gated ion channel tends to be open for some values of the membrane potential, and closed for others. In most cases, however, the relationship between membrane potential and channel state is probabilistic and involves a time delay. Ion channels switch between conformations at unpredictable times: The membrane potential determines the rate of transitions and the probability per unit time of each type of transition. Voltage-gated ion channels are capable of producing action potentials because they can give rise to
positive feedback Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop which exacerbates the effects of a small disturbance. That is, the effects of a perturbation on a system include an increase in the ...
loops: The membrane potential controls the state of the ion channels, but the state of the ion channels controls the membrane potential. Thus, in some situations, a rise in the membrane potential can cause ion channels to open, thereby causing a further rise in the membrane potential. An action potential occurs when this positive feedback cycle (
Hodgkin cycle In membrane biology, the Hodgkin cycle is a key component of membrane physiology that describes bioelectrical impulses, especially prevalent in neural and muscle tissues. It was identified by British physiologist and biophysicist Sir Alan Lloy ...
) proceeds explosively. The time and amplitude trajectory of the action potential are determined by the biophysical properties of the voltage-gated ion channels that produce it. Several types of channels capable of producing the positive feedback necessary to generate an action potential do exist. Voltage-gated sodium channels are responsible for the fast action potentials involved in nerve conduction. Slower action potentials in muscle cells and some types of neurons are generated by voltage-gated calcium channels. Each of these types comes in multiple variants, with different voltage sensitivity and different temporal dynamics. The most intensively studied type of voltage-dependent ion channels comprises the sodium channels involved in fast nerve conduction. These are sometimes known as Hodgkin-Huxley sodium channels because they were first characterized by
Alan Hodgkin Sir Alan Lloyd Hodgkin (5 February 1914 – 20 December 1998) was an English physiologist and biophysicist who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles. Early life and education Hodgkin was bo ...
and
Andrew Huxley Sir Andrew Fielding Huxley (22 November 191730 May 2012) was an English physiologist and biophysicist. He was born into the prominent Huxley family. After leaving Westminster School in central London, he went to Trinity College, Cambridge ...
in their Nobel Prize-winning studies of the biophysics of the action potential, but can more conveniently be referred to as ''Na''V channels. (The "V" stands for "voltage".) An ''Na''V channel has three possible states, known as ''deactivated'', ''activated'', and ''inactivated''. The channel is permeable only to sodium ions when it is in the ''activated'' state. When the membrane potential is low, the channel spends most of its time in the ''deactivated'' (closed) state. If the membrane potential is raised above a certain level, the channel shows increased probability of transitioning to the ''activated'' (open) state. The higher the membrane potential the greater the probability of activation. Once a channel has activated, it will eventually transition to the ''inactivated'' (closed) state. It tends then to stay inactivated for some time, but, if the membrane potential becomes low again, the channel will eventually transition back to the ''deactivated'' state. During an action potential, most channels of this type go through a cycle ''deactivated''→''activated''→''inactivated''→''deactivated''. This is only the population average behavior, however – an individual channel can in principle make any transition at any time. However, the likelihood of a channel's transitioning from the ''inactivated'' state directly to the ''activated'' state is very low: A channel in the ''inactivated'' state is refractory until it has transitioned back to the ''deactivated'' state. The outcome of all this is that the kinetics of the ''Na''V channels are governed by a transition matrix whose rates are voltage-dependent in a complicated way. Since these channels themselves play a major role in determining the voltage, the global dynamics of the system can be quite difficult to work out. Hodgkin and Huxley approached the problem by developing a set of
differential equation In mathematics, a differential equation is an equation that relates one or more unknown functions and their derivatives. In applications, the functions generally represent physical quantities, the derivatives represent their rates of change, an ...
s for the parameters that govern the ion channel states, known as the Hodgkin-Huxley equations. These equations have been extensively modified by later research, but form the starting point for most theoretical studies of action potential biophysics. As the membrane potential is increased, sodium ion channels open, allowing the entry of
sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
ions into the cell. This is followed by the opening of potassium ion channels that permit the exit of
potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
ions from the cell. The inward flow of sodium ions increases the concentration of positively charged
cation An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
s in the cell and causes depolarization, where the potential of the cell is higher than the cell's
resting potential A relatively static membrane potential which is usually referred to as the ground value for trans-membrane voltage. The relatively static membrane potential of quiescent cells is called the resting membrane potential (or resting voltage), as opp ...
. The sodium channels close at the peak of the action potential, while potassium continues to leave the cell. The efflux of potassium ions decreases the membrane potential or hyperpolarizes the cell. For small voltage increases from rest, the potassium current exceeds the sodium current and the voltage returns to its normal resting value, typically −70 mV. However, if the voltage increases past a critical threshold, typically 15 mV higher than the resting value, the sodium current dominates. This results in a runaway condition whereby the
positive feedback Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop which exacerbates the effects of a small disturbance. That is, the effects of a perturbation on a system include an increase in the ...
from the sodium current activates even more sodium channels. Thus, the cell ''fires'', producing an action potential. The frequency at which a neuron elicits action potentials is often referred to as a firing rate or neural firing rate. Currents produced by the opening of voltage-gated channels in the course of an action potential are typically significantly larger than the initial stimulating current. Thus, the amplitude, duration, and shape of the action potential are determined largely by the properties of the excitable membrane and not the amplitude or duration of the stimulus. This all-or-nothing property of the action potential sets it apart from
graded potential Graded potentials are changes in membrane potential that vary in size, as opposed to being all-or-none. They include diverse potentials such as receptor potentials, electrotonic potentials, subthreshold membrane potential oscillations, slow-wave ...
s such as
receptor potential A receptor potential, also known as a generator potential, a type of graded potential, is the transmembrane potential difference produced by activation of a sensory receptor. A receptor potential is often produced by sensory transduction. It is gen ...
s,
electrotonic potential In physiology, electrotonus refers to the passive spread of charge inside a neuron and between cardiac muscle cells or smooth muscle cells. ''Passive'' means that voltage-dependent changes in membrane conductance do not contribute. Neurons and oth ...
s, subthreshold membrane potential oscillations, and synaptic potentials, which scale with the magnitude of the stimulus. A variety of action potential types exist in many cell types and cell compartments as determined by the types of voltage-gated channels,
leak channels The two-pore-domain or tandem pore domain potassium channels are a family of 15 members that form what is known as leak channels which possess Goldman-Hodgkin-Katz (open) rectification. These channels are regulated by several mechanisms including ...
, channel distributions, ionic concentrations, membrane capacitance, temperature, and other factors. The principal ions involved in an action potential are sodium and potassium cations; sodium ions enter the cell, and potassium ions leave, restoring equilibrium. Relatively few ions need to cross the membrane for the membrane voltage to change drastically. The ions exchanged during an action potential, therefore, make a negligible change in the interior and exterior ionic concentrations. The few ions that do cross are pumped out again by the continuous action of the
sodium–potassium pump The sodium–potassium pump (sodium–potassium adenosine triphosphatase, also known as Na⁺/K⁺-ATPase, Na⁺/K⁺ pump, or sodium–potassium ATPase) is an enzyme (an electrogenic transmembrane ATPase) found in the membrane of all animal c ...
, which, with other
ion transporter In biology, a transporter is a transmembrane protein that moves ions (or other small molecules) across a biological membrane to accomplish many different biological functions including, cellular communication, maintaining homeostasis, energy produ ...
s, maintains the normal ratio of ion concentrations across the membrane.
Calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
cations and
chloride The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride salts ...
anion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
s are involved in a few types of action potentials, such as the
cardiac action potential The cardiac action potential is a brief change in voltage ( membrane potential) across the cell membrane of heart cells. This is caused by the movement of charged atoms (called ions) between the inside and outside of the cell, through proteins c ...
and the action potential in the single-cell
alga Algae (; singular alga ) is an informal term for a large and diverse group of photosynthetic eukaryotic organisms. It is a polyphyletic grouping that includes species from multiple distinct clades. Included organisms range from unicellular mi ...
''
Acetabularia ''Acetabularia'' is a genus of green algae in the family Polyphysaceae, Typically found in subtropical waters, ''Acetabularia'' is a single-celled organism, but gigantic in size and complex in form, making it an excellent model organism for stu ...
'', respectively. Although action potentials are generated locally on patches of excitable membrane, the resulting currents can trigger action potentials on neighboring stretches of membrane, precipitating a domino-like propagation. In contrast to passive spread of electric potentials (
electrotonic potential In physiology, electrotonus refers to the passive spread of charge inside a neuron and between cardiac muscle cells or smooth muscle cells. ''Passive'' means that voltage-dependent changes in membrane conductance do not contribute. Neurons and oth ...
), action potentials are generated anew along excitable stretches of membrane and propagate without decay. Schmidt-Nielsen, p. 484. Myelinated sections of axons are not excitable and do not produce action potentials and the signal is propagated passively as
electrotonic potential In physiology, electrotonus refers to the passive spread of charge inside a neuron and between cardiac muscle cells or smooth muscle cells. ''Passive'' means that voltage-dependent changes in membrane conductance do not contribute. Neurons and oth ...
. Regularly spaced unmyelinated patches, called the
nodes of Ranvier In neuroscience and anatomy, nodes of Ranvier ( ), also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated and highly enriched in ion channels, al ...
, generate action potentials to boost the signal. Known as
saltatory conduction In neuroscience, saltatory conduction () is the propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials. The uninsulated nodes of Ranvier are th ...
, this type of signal propagation provides a favorable tradeoff of signal velocity and axon diameter. Depolarization of
axon terminal Axon terminals (also called synaptic boutons, terminal boutons, or end-feet) are distal terminations of the telodendria (branches) of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell, or neuron, that condu ...
s, in general, triggers the release of
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...
into the
synaptic cleft Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...
. In addition, backpropagating action potentials have been recorded in the dendrites of
pyramidal neurons Pyramidal cells, or pyramidal neurons, are a type of multipolar neuron found in areas of the brain including the cerebral cortex, the hippocampus, and the amygdala. Pyramidal neurons are the primary excitation units of the mammalian prefrontal cor ...
, which are ubiquitous in the neocortex. These are thought to have a role in
spike-timing-dependent plasticity Spike-timing-dependent plasticity (STDP) is a biological process that adjusts the strength of connections between neurons in the brain. The process adjusts the connection strengths based on the relative timing of a particular neuron's output and in ...
. In the Hodgkin–Huxley membrane capacitance model, the speed of transmission of an action potential was undefined and it was assumed that adjacent areas became depolarized due to released ion interference with neighbouring channels. Measurements of ion diffusion and radii have since shown this not to be possible. Moreover, contradictory measurements of entropy changes and timing disputed the capacitance model as acting alone. Alternatively, Gilbert Ling's adsorption hypothesis, posits that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto adsorption sites of cells.


Maturation of the electrical properties of the action potential

A
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
's ability to generate and propagate an action potential changes during
development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material is reshaped * Photograph ...
. How much the membrane potential of a neuron changes as the result of a current impulse is a function of the membrane
input resistance The input impedance of an electrical network is the measure of the opposition to current ( impedance), both static ( resistance) and dynamic ( reactance), into the load network that is ''external'' to the electrical source. The input admittance (the ...
. As a cell grows, more
channels Channel, channels, channeling, etc., may refer to: Geography * Channel (geography), in physical geography, a landform consisting of the outline (banks) of the path of a narrow body of water. Australia * Channel Country, region of outback Austral ...
are added to the membrane, causing a decrease in input resistance. A mature neuron also undergoes shorter changes in membrane potential in response to synaptic currents. Neurons from a ferret
lateral geniculate nucleus In neuroanatomy, the lateral geniculate nucleus (LGN; also called the lateral geniculate body or lateral geniculate complex) is a structure in the thalamus and a key component of the mammalian visual pathway. It is a small, ovoid, ventral projec ...
have a longer
time constant In physics and engineering, the time constant, usually denoted by the Greek letter (tau), is the parameter characterizing the response to a step input of a first-order, linear time-invariant (LTI) system.Concretely, a first-order LTI system is a sy ...
and larger
voltage Voltage, also known as electric pressure, electric tension, or (electric) potential difference, is the difference in electric potential between two points. In a static electric field, it corresponds to the work needed per unit of charge to m ...
deflection at P0 than they do at P30. One consequence of the decreasing action potential duration is that the fidelity of the signal can be preserved in response to high frequency stimulation. Immature neurons are more prone to synaptic depression than potentiation after high frequency stimulation. In the early development of many organisms, the action potential is actually initially carried by calcium current rather than sodium current. The opening and closing kinetics of calcium channels during development are slower than those of the voltage-gated sodium channels that will carry the action potential in the mature neurons. The longer opening times for the calcium channels can lead to action potentials that are considerably slower than those of mature neurons.
Xenopus ''Xenopus'' () (Gk., ξενος, ''xenos''=strange, πους, ''pous''=foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-known ...
neurons initially have action potentials that take 60–90 ms. During development, this time decreases to 1 ms. There are two reasons for this drastic decrease. First, the inward current becomes primarily carried by sodium channels. Second, the delayed rectifier, a
potassium channel Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cel ...
current, increases to 3.5 times its initial strength. In order for the transition from a calcium-dependent action potential to a sodium-dependent action potential to proceed new channels must be added to the membrane. If Xenopus neurons are grown in an environment with
RNA synthesis Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called ...
or
protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
inhibitors that transition is prevented. Even the electrical activity of the cell itself may play a role in channel expression. If action potentials in Xenopus
myocyte A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...
s are blocked, the typical increase in sodium and potassium current density is prevented or delayed. This maturation of electrical properties is seen across species. Xenopus sodium and potassium currents increase drastically after a neuron goes through its final phase of
mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
. The sodium current density of rat
cortical neurons The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...
increases by 600% within the first two postnatal weeks.


Neurotransmission


Anatomy of a neuron

Several types of cells support an action potential, such as plant cells, muscle cells, and the specialized cells of the heart (in which occurs the
cardiac action potential The cardiac action potential is a brief change in voltage ( membrane potential) across the cell membrane of heart cells. This is caused by the movement of charged atoms (called ions) between the inside and outside of the cell, through proteins c ...
). However, the main excitable cell is the
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
, which also has the simplest mechanism for the action potential. Neurons are electrically excitable cells composed, in general, of one or more dendrites, a single
soma Soma may refer to: Businesses and brands * SOMA (architects), a New York–based firm of architects * Soma (company), a company that designs eco-friendly water filtration systems * SOMA Fabrications, a builder of bicycle frames and other bicycle ...
, a single axon and one or more
axon terminal Axon terminals (also called synaptic boutons, terminal boutons, or end-feet) are distal terminations of the telodendria (branches) of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell, or neuron, that condu ...
s. Dendrites are cellular projections whose primary function is to receive synaptic signals. Their protrusions, known as
dendritic spine A dendritic spine (or spine) is a small membranous protrusion from a neuron's dendrite that typically receives input from a single axon at the synapse. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical s ...
s, are designed to capture the neurotransmitters released by the presynaptic neuron. They have a high concentration of
ligand-gated ion channel Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...
s. These spines have a thin neck connecting a bulbous protrusion to the dendrite. This ensures that changes occurring inside the spine are less likely to affect the neighboring spines. The dendritic spine can, with rare exception (see
LTP LTP may refer to: Biology and medicine * Lateral tibial plateau, part of a leg bone * Lipid transfer proteins, proteins found in plant tissues * Long-term potentiation (neurophysiology), a long-lasting enhancement in signal transmission between ...
), act as an independent unit. The dendrites extend from the soma, which houses the
nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom * Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...
, and many of the "normal"
eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
organelles. Unlike the spines, the surface of the soma is populated by voltage activated ion channels. These channels help transmit the signals generated by the dendrites. Emerging out from the soma is the
axon hillock The axon hillock is a specialized part of the cell body (or soma) of a neuron that connects to the axon. It can be identified using light microscopy from its appearance and location in a neuron and from its sparse distribution of Nissl substance. ...
. This region is characterized by having a very high concentration of voltage-activated sodium channels. In general, it is considered to be the spike initiation zone for action potentials, i.e. the
trigger zone In neuroscience and neurology, a trigger zone is an area in the body, or of a cell, in which a specific type of stimulation triggers a specific type of response. The term was first used in this context around 1914 by Hugh T. Patrick, who was writin ...
. Multiple signals generated at the spines, and transmitted by the soma all converge here. Immediately after the axon hillock is the axon. This is a thin tubular protrusion traveling away from the soma. The axon is insulated by a
myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...
sheath. Myelin is composed of either
Schwann cells Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory en ...
(in the peripheral nervous system) or
oligodendrocytes Oligodendrocytes (), or oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons in the central nervous system of jawed vertebrates, equivalent to the function performed by Schwann cells in the ...
(in the central nervous system), both of which are types of
glial cells Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myel ...
. Although glial cells are not involved with the transmission of electrical signals, they communicate and provide important biochemical support to neurons. To be specific, myelin wraps multiple times around the axonal segment, forming a thick fatty layer that prevents ions from entering or escaping the axon. This insulation prevents significant signal decay as well as ensuring faster signal speed. This insulation, however, has the restriction that no channels can be present on the surface of the axon. There are, therefore, regularly spaced patches of membrane, which have no insulation. These
nodes of Ranvier In neuroscience and anatomy, nodes of Ranvier ( ), also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated and highly enriched in ion channels, al ...
can be considered to be "mini axon hillocks", as their purpose is to boost the signal in order to prevent significant signal decay. At the furthest end, the axon loses its insulation and begins to branch into several
axon terminal Axon terminals (also called synaptic boutons, terminal boutons, or end-feet) are distal terminations of the telodendria (branches) of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell, or neuron, that condu ...
s. These presynaptic terminals, or synaptic boutons, are a specialized area within the axon of the presynaptic cell that contains
neurotransmitters A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neur ...
enclosed in small membrane-bound spheres called
synaptic vesicle In a neuron, synaptic vesicles (or neurotransmitter vesicles) store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulse ...
s.


Initiation

Before considering the propagation of action potentials along
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...
s and their termination at the synaptic knobs, it is helpful to consider the methods by which action potentials can be initiated at the
axon hillock The axon hillock is a specialized part of the cell body (or soma) of a neuron that connects to the axon. It can be identified using light microscopy from its appearance and location in a neuron and from its sparse distribution of Nissl substance. ...
. The basic requirement is that the membrane voltage at the hillock be raised above the threshold for firing. There are several ways in which this depolarization can occur.


Dynamics

Action potentials are most commonly initiated by
excitatory postsynaptic potential In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, caused by the ...
s from a presynaptic neuron. Typically,
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...
molecules are released by the
presynaptic In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
. These neurotransmitters then bind to receptors on the postsynaptic cell. This binding opens various types of
ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
s. This opening has the further effect of changing the local permeability of the
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
and, thus, the membrane potential. If the binding increases the voltage (depolarizes the membrane), the synapse is excitatory. If, however, the binding decreases the voltage (hyperpolarizes the membrane), it is inhibitory. Whether the voltage is increased or decreased, the change propagates passively to nearby regions of the membrane (as described by the cable equation and its refinements). Typically, the voltage stimulus decays exponentially with the distance from the synapse and with time from the binding of the neurotransmitter. Some fraction of an excitatory voltage may reach the
axon hillock The axon hillock is a specialized part of the cell body (or soma) of a neuron that connects to the axon. It can be identified using light microscopy from its appearance and location in a neuron and from its sparse distribution of Nissl substance. ...
and may (in rare cases) depolarize the membrane enough to provoke a new action potential. More typically, the excitatory potentials from several synapses must work together at nearly the same time to provoke a new action potential. Their joint efforts can be thwarted, however, by the counteracting
inhibitory postsynaptic potential An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential.Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Incorporated; 2008. ...
s. Neurotransmission can also occur through
electrical synapse Electricity is the set of physical phenomena associated with the presence and motion of matter that has a property of electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as described by ...
s. Due to the direct connection between excitable cells in the form of gap junctions, an action potential can be transmitted directly from one cell to the next in either direction. The free flow of ions between cells enables rapid non-chemical-mediated transmission. Rectifying channels ensure that action potentials move only in one direction through an electrical synapse. Electrical synapses are found in all nervous systems, including the human brain, although they are a distinct minority.


"All-or-none" principle

The
amplitude The amplitude of a periodic variable is a measure of its change in a single period (such as time or spatial period). The amplitude of a non-periodic signal is its magnitude compared with a reference value. There are various definitions of amplit ...
of an action potential is often thought to be independent of the amount of current that produced it. In other words, larger currents do not create larger action potentials. Therefore, action potentials are said to be
all-or-none All or none (AON) is a finance term used in investment banking or securities transactions that refers to "an order to buy or sell a stock that must be executed in its entirety, or not executed at all". Partial execution is not acceptable; the order ...
signals, since either they occur fully or they do not occur at all.Sasaki, T., Matsuki, N., Ikegaya, Y. 2011 Action-potential modulation during axonal conduction Science 331 (6017), pp. 599–601Aur D., Jog, MS., 2010 Neuroelectrodynamics: Understanding the brain language, IOS Press, 2010. This is in contrast to
receptor potential A receptor potential, also known as a generator potential, a type of graded potential, is the transmembrane potential difference produced by activation of a sensory receptor. A receptor potential is often produced by sensory transduction. It is gen ...
s, whose amplitudes are dependent on the intensity of a stimulus. In both cases, the
frequency Frequency is the number of occurrences of a repeating event per unit of time. It is also occasionally referred to as ''temporal frequency'' for clarity, and is distinct from ''angular frequency''. Frequency is measured in hertz (Hz) which is eq ...
of action potentials is correlated with the intensity of a stimulus. Despite the classical view of the action potential as a stereotyped, uniform signal having dominated the field of neuroscience for many decades, newer evidence does suggest that action potentials are more complex events indeed capable of transmitting information through not just their amplitude, but their duration and phase as well, sometimes even up to distances originally not thought to be possible.


Sensory neurons

In
sensory neurons Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded potentials. This process is called sensory transduction. The ...
, an external signal such as pressure, temperature, light, or sound is coupled with the opening and closing of
ion channels Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
, which in turn alter the ionic permeabilities of the membrane and its voltage. These voltage changes can again be excitatory (depolarizing) or inhibitory (hyperpolarizing) and, in some sensory neurons, their combined effects can depolarize the axon hillock enough to provoke action potentials. Some examples in humans include the
olfactory receptor neuron An olfactory receptor neuron (ORN), also called an olfactory sensory neuron (OSN), is a sensory neuron within the olfactory system. Structure Humans have between 10 and 20 million olfactory receptor neurons (ORNs). In vertebrates, ORNs are b ...
and
Meissner's corpuscle Tactile corpuscles or Meissner's corpuscles are a type of mechanoreceptor discovered by anatomist Georg Meissner (1829–1905) and Rudolf Wagner. This corpuscle is a type of nerve ending in the skin that is responsible for sensitivity to pressur ...
, which are critical for the sense of smell and
touch In physiology, the somatosensory system is the network of neural structures in the brain and body that produce the perception of touch ( haptic perception), as well as temperature ( thermoception), body position (proprioception), and pain. It ...
, respectively. However, not all sensory neurons convert their external signals into action potentials; some do not even have an axon. Instead, they may convert the signal into the release of a
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...
, or into continuous
graded potentials Graded potentials are changes in membrane potential that vary in size, as opposed to being all-or-none law, all-or-none. They include diverse potentials such as receptor potentials, electrotonic potentials, subthreshold membrane potential oscillat ...
, either of which may stimulate subsequent neuron(s) into firing an action potential. For illustration, in the human
ear An ear is the organ that enables hearing and, in mammals, body balance using the vestibular system. In mammals, the ear is usually described as having three parts—the outer ear, the middle ear and the inner ear. The outer ear consists of ...
,
hair cell Hair cells are the sensory receptors of both the auditory system and the vestibular system in the ears of all vertebrates, and in the lateral line organ of fishes. Through mechanotransduction, hair cells detect movement in their environment. ...
s convert the incoming sound into the opening and closing of mechanically gated ion channels, which may cause
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...
molecules to be released. In similar manner, in the human
retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...
, the initial
photoreceptor cell A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light (visible electromagnetic radiatio ...
s and the next layer of cells (comprising
bipolar cell A bipolar neuron, or bipolar cell, is a type of neuron that has two extensions (one axon and one dendrite). Many bipolar cells are specialized sensory neurons for the transmission of sense. As such, they are part of the sensory pathways for smell ...
s and
horizontal cell Horizontal cells are the laterally interconnecting neurons having cell bodies in the inner nuclear layer of the retina of vertebrate eyes. They help integrate and regulate the input from multiple photoreceptor cells. Among their functions, hori ...
s) do not produce action potentials; only some
amacrine cell Amacrine cells are interneurons in the retina. They are named from the Greek roots ''a–'' ("non"), ''makr–'' ("long") and ''in–'' ("fiber"), because of their short neuronal processes. Amacrine cells are inhibitory neurons, and they proj ...
s and the third layer, the
ganglion cell {{stack, A ganglion cell is a cell found in a ganglion. Examples of ganglion cells include: * Retinal ganglion cell (RGC) found in the ganglion cell layer of the retina * Cells that reside in the adrenal medulla, where they are involved in the ...
s, produce action potentials, which then travel up the
optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual information from the retina to the brain. In humans, the optic nerve is derived fro ...
.


Pacemaker potentials

In sensory neurons, action potentials result from an external stimulus. However, some excitable cells require no such stimulus to fire: They spontaneously depolarize their axon hillock and fire action potentials at a regular rate, like an internal clock. The voltage traces of such cells are known as
pacemaker potential In the pacemaking cells of the heart (e.g., the sinoatrial node), the pacemaker potential (also called the pacemaker current) is the slow, positive increase in voltage across the cell's membrane (the membrane potential) that occurs between the en ...
s. The
cardiac pacemaker 350px, Image showing the cardiac pacemaker or SA node, the primary pacemaker within the electrical_conduction_system_of_the_heart">SA_node,_the_primary_pacemaker_within_the_electrical_conduction_system_of_the_heart. The_muscle_contraction.htm ...
cells of the
sinoatrial node The sinoatrial node (also known as the sinuatrial node, SA node or sinus node) is an oval shaped region of special cardiac muscle in the upper back wall of the right atrium made up of cells known as pacemaker cells. The sinus node is approximat ...
in the
heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
provide a good example. Although such pacemaker potentials have a natural rhythm, it can be adjusted by external stimuli; for instance,
heart rate Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and excr ...
can be altered by pharmaceuticals as well as signals from the sympathetic and
parasympathetic The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of t ...
nerves. The external stimuli do not cause the cell's repetitive firing, but merely alter its timing. In some cases, the regulation of frequency can be more complex, leading to patterns of action potentials, such as bursting.


Phases

The course of the action potential can be divided into five parts: the rising phase, the peak phase, the falling phase, the undershoot phase, and the refractory period. During the rising phase the membrane potential depolarizes (becomes more positive). The point at which
depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is ess ...
stops is called the peak phase. At this stage, the membrane potential reaches a maximum. Subsequent to this, there is a falling phase. During this stage the membrane potential becomes more negative, returning towards resting potential. The undershoot, or
afterhyperpolarization Afterhyperpolarization, or AHP, is the hyperpolarizing phase of a neuron's action potential where the cell's membrane potential falls below the normal resting potential. This is also commonly referred to as an action potential's undershoot phas ...
, phase is the period during which the membrane potential temporarily becomes more negatively charged than when at rest (hyperpolarized). Finally, the time during which a subsequent action potential is impossible or difficult to fire is called the refractory period, which may overlap with the other phases. The course of the action potential is determined by two coupled effects. First, voltage-sensitive ion channels open and close in response to changes in the
membrane voltage Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges ...
''Vm''. This changes the membrane's permeability to those ions. Second, according to the
Goldman equation The Goldman–Hodgkin–Katz voltage equation, more commonly known as the Goldman equation, is used in cell membrane physiology to determine the reversal potential across a cell's membrane, taking into account all of the ions that are permeant t ...
, this change in permeability changes the equilibrium potential ''Em'', and, thus, the membrane voltage ''Vm''. Thus, the membrane potential affects the permeability, which then further affects the membrane potential. This sets up the possibility for
positive feedback Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop which exacerbates the effects of a small disturbance. That is, the effects of a perturbation on a system include an increase in the ...
, which is a key part of the rising phase of the action potential. A complicating factor is that a single ion channel may have multiple internal "gates" that respond to changes in ''Vm'' in opposite ways, or at different rates. For example, although raising ''Vm'' ''opens'' most gates in the voltage-sensitive sodium channel, it also ''closes'' the channel's "inactivation gate", albeit more slowly. Hence, when ''Vm'' is raised suddenly, the sodium channels open initially, but then close due to the slower inactivation. The voltages and currents of the action potential in all of its phases were modeled accurately by
Alan Lloyd Hodgkin Sir Alan Lloyd Hodgkin (5 February 1914 – 20 December 1998) was an English physiologist and biophysicist who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles. Early life and education Hodgkin was ...
and
Andrew Huxley Sir Andrew Fielding Huxley (22 November 191730 May 2012) was an English physiologist and biophysicist. He was born into the prominent Huxley family. After leaving Westminster School in central London, he went to Trinity College, Cambridge ...
in 1952, for which they were awarded the
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
in 1963. However, their model considers only two types of voltage-sensitive ion channels, and makes several assumptions about them, e.g., that their internal gates open and close independently of one another. In reality, there are many types of ion channels,Goldin, AL in and they do not always open and close independently.


Stimulation and rising phase

A typical action potential begins at the
axon hillock The axon hillock is a specialized part of the cell body (or soma) of a neuron that connects to the axon. It can be identified using light microscopy from its appearance and location in a neuron and from its sparse distribution of Nissl substance. ...
with a sufficiently strong depolarization, e.g., a stimulus that increases ''Vm''. This depolarization is often caused by the injection of extra sodium
cation An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
s into the cell; these cations can come from a wide variety of sources, such as
chemical synapse Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syst ...
s,
sensory neuron Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded potentials. This process is called sensory transduction. The cell ...
s or
pacemaker potential In the pacemaking cells of the heart (e.g., the sinoatrial node), the pacemaker potential (also called the pacemaker current) is the slow, positive increase in voltage across the cell's membrane (the membrane potential) that occurs between the en ...
s. For a neuron at rest, there is a high concentration of sodium and chloride ions in the
extracellular fluid In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 60% (range 45 to 75%) of total body weight; women and the obese typically have a lower ...
compared to the
intracellular fluid The human body and even its individual body fluids may be conceptually divided into various fluid compartments, which, although not literally anatomic compartments, do represent a real division in terms of how portions of the body's water, solute ...
, while there is a high concentration of potassium ions in the intracellular fluid compared to the extracellular fluid. The difference in concentrations, which causes ions to move from a high to a low concentration, and electrostatic effects (attraction of opposite charges) are responsible for the movement of ions in and out of the neuron. The inside of a neuron has a negative charge, relative to the cell exterior, from the movement of K+ out of the cell. The neuron membrane is more permeable to K+ than to other ions, allowing this ion to selectively move out of the cell, down its concentration gradient. This concentration gradient along with potassium leak channels present on the membrane of the neuron causes an efflux of potassium ions making the resting potential close to ''E''K ≈ –75 mV. Since Na+ ions are in higher concentrations outside of the cell, the concentration and voltage differences both drive them into the cell when Na+ channels open. Depolarization opens both the sodium and potassium channels in the membrane, allowing the ions to flow into and out of the axon, respectively. If the depolarization is small (say, increasing ''Vm'' from −70 mV to −60 mV), the outward potassium current overwhelms the inward sodium current and the membrane repolarizes back to its normal resting potential around −70 mV. However, if the depolarization is large enough, the inward sodium current increases more than the outward potassium current and a runaway condition (
positive feedback Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop which exacerbates the effects of a small disturbance. That is, the effects of a perturbation on a system include an increase in the ...
) results: the more inward current there is, the more ''Vm'' increases, which in turn further increases the inward current. A sufficiently strong depolarization (increase in ''Vm'') causes the voltage-sensitive sodium channels to open; the increasing permeability to sodium drives ''Vm'' closer to the sodium equilibrium voltage ''E''Na≈ +55 mV. The increasing voltage in turn causes even more sodium channels to open, which pushes ''Vm'' still further towards ''E''Na. This positive feedback continues until the sodium channels are fully open and ''Vm'' is close to ''E''Na. The sharp rise in ''Vm'' and sodium permeability correspond to the ''rising phase'' of the action potential. The critical threshold voltage for this runaway condition is usually around −45 mV, but it depends on the recent activity of the axon. A cell that has just fired an action potential cannot fire another one immediately, since the Na+ channels have not recovered from the inactivated state. The period during which no new action potential can be fired is called the ''absolute refractory period''. At longer times, after some but not all of the ion channels have recovered, the axon can be stimulated to produce another action potential, but with a higher threshold, requiring a much stronger depolarization, e.g., to −30 mV. The period during which action potentials are unusually difficult to evoke is called the ''relative refractory period''.


Peak phase

The positive feedback of the rising phase slows and comes to a halt as the sodium ion channels become maximally open. At the peak of the action potential, the sodium permeability is maximized and the membrane voltage ''Vm'' is nearly equal to the sodium equilibrium voltage ''E''Na. However, the same raised voltage that opened the sodium channels initially also slowly shuts them off, by closing their pores; the sodium channels become ''inactivated''. This lowers the membrane's permeability to sodium relative to potassium, driving the membrane voltage back towards the resting value. At the same time, the raised voltage opens voltage-sensitive potassium channels; the increase in the membrane's potassium permeability drives ''Vm'' towards ''E''K. Combined, these changes in sodium and potassium permeability cause ''Vm'' to drop quickly, repolarizing the membrane and producing the "falling phase" of the action potential.


Afterhyperpolarization

The depolarized voltage opens additional voltage-dependent potassium channels, and some of these do not close right away when the membrane returns to its normal resting voltage. In addition, further potassium channels open in response to the influx of calcium ions during the action potential. The intracellular concentration of potassium ions is transiently unusually low, making the membrane voltage ''Vm'' even closer to the potassium equilibrium voltage ''E''K. The membrane potential goes below the resting membrane potential. Hence, there is an undershoot or hyperpolarization, termed an
afterhyperpolarization Afterhyperpolarization, or AHP, is the hyperpolarizing phase of a neuron's action potential where the cell's membrane potential falls below the normal resting potential. This is also commonly referred to as an action potential's undershoot phas ...
, that persists until the membrane potassium permeability returns to its usual value, restoring the membrane potential to the resting state.


Refractory period

Each action potential is followed by a refractory period, which can be divided into an ''absolute refractory period'', during which it is impossible to evoke another action potential, and then a ''relative refractory period'', during which a stronger-than-usual stimulus is required. These two refractory periods are caused by changes in the state of sodium and potassium channel molecules. When closing after an action potential, sodium channels enter an "inactivated" state, in which they cannot be made to open regardless of the membrane potential—this gives rise to the absolute refractory period. Even after a sufficient number of sodium channels have transitioned back to their resting state, it frequently happens that a fraction of potassium channels remains open, making it difficult for the membrane potential to depolarize, and thereby giving rise to the relative refractory period. Because the density and subtypes of potassium channels may differ greatly between different types of neurons, the duration of the relative refractory period is highly variable. The absolute refractory period is largely responsible for the unidirectional propagation of action potentials along axons. At any given moment, the patch of axon behind the actively spiking part is refractory, but the patch in front, not having been activated recently, is capable of being stimulated by the depolarization from the action potential.


Propagation

The action potential generated at the axon hillock propagates as a wave along the axon. The currents flowing inwards at a point on the axon during an action potential spread out along the axon, and depolarize the adjacent sections of its membrane. If sufficiently strong, this depolarization provokes a similar action potential at the neighboring membrane patches. This basic mechanism was demonstrated by
Alan Lloyd Hodgkin Sir Alan Lloyd Hodgkin (5 February 1914 – 20 December 1998) was an English physiologist and biophysicist who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles. Early life and education Hodgkin was ...
in 1937. After crushing or cooling nerve segments and thus blocking the action potentials, he showed that an action potential arriving on one side of the block could provoke another action potential on the other, provided that the blocked segment was sufficiently short.
*
Once an action potential has occurred at a patch of membrane, the membrane patch needs time to recover before it can fire again. At the molecular level, this ''absolute refractory period'' corresponds to the time required for the voltage-activated sodium channels to recover from inactivation, i.e., to return to their closed state. There are many types of voltage-activated potassium channels in neurons. Some of them inactivate fast (A-type currents) and some of them inactivate slowly or not inactivate at all; this variability guarantees that there will be always an available source of current for repolarization, even if some of the potassium channels are inactivated because of preceding depolarization. On the other hand, all neuronal voltage-activated sodium channels inactivate within several milliseconds during strong depolarization, thus making following depolarization impossible until a substantial fraction of sodium channels have returned to their closed state. Although it limits the frequency of firing, the absolute refractory period ensures that the action potential moves in only one direction along an axon. The currents flowing in due to an action potential spread out in both directions along the axon. However, only the unfired part of the axon can respond with an action potential; the part that has just fired is unresponsive until the action potential is safely out of range and cannot restimulate that part. In the usual orthodromic conduction, the action potential propagates from the axon hillock towards the synaptic knobs (the axonal termini); propagation in the opposite direction—known as antidromic conduction—is very rare. However, if a laboratory axon is stimulated in its middle, both halves of the axon are "fresh", i.e., unfired; then two action potentials will be generated, one traveling towards the axon hillock and the other traveling towards the synaptic knobs.


Myelin and saltatory conduction

In order to enable fast and efficient transduction of electrical signals in the nervous system, certain neuronal axons are covered with
myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...
sheaths. Myelin is a multilamellar membrane that enwraps the axon in segments separated by intervals known as
nodes of Ranvier In neuroscience and anatomy, nodes of Ranvier ( ), also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated and highly enriched in ion channels, al ...
. It is produced by specialized cells:
Schwann cell Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensh ...
s exclusively in the
peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...
, and
oligodendrocyte Oligodendrocytes (), or oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons in the central nervous system of jawed vertebrates, equivalent to the function performed by Schwann cells in the ...
s exclusively in the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
. Myelin sheath reduces membrane capacitance and increases membrane resistance in the inter-node intervals, thus allowing a fast, saltatory movement of action potentials from node to node. Myelination is found mainly in
vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...
s, but an analogous system has been discovered in a few invertebrates, such as some species of
shrimp Shrimp are crustaceans (a form of shellfish) with elongated bodies and a primarily swimming mode of locomotion – most commonly Caridea and Dendrobranchiata of the decapod order, although some crustaceans outside of this order are refer ...
. Not all neurons in vertebrates are myelinated; for example, axons of the neurons comprising the autonomous nervous system are not, in general, myelinated. Myelin prevents ions from entering or leaving the axon along myelinated segments. As a general rule, myelination increases the
conduction velocity In neuroscience, nerve conduction velocity (CV) is an important aspect of nerve conduction studies. It is the speed at which an electrochemical impulse propagates down a neural pathway. Conduction velocities are affected by a wide array of factor ...
of action potentials and makes them more energy-efficient. Whether saltatory or not, the mean conduction velocity of an action potential ranges from 1 
meter per second The metre per second is the unit of both speed (a scalar quantity) and velocity (a vector quantity, which has direction and magnitude) in the International System of Units (SI), equal to the speed of a body covering a distance of one metre in ...
(m/s) to over 100 m/s, and, in general, increases with axonal diameter. Action potentials cannot propagate through the membrane in myelinated segments of the axon. However, the current is carried by the cytoplasm, which is sufficient to depolarize the first or second subsequent
node of Ranvier In neuroscience and anatomy, nodes of Ranvier ( ), also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated and highly enriched in ion channels, al ...
. Instead, the ionic current from an action potential at one
node of Ranvier In neuroscience and anatomy, nodes of Ranvier ( ), also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated and highly enriched in ion channels, al ...
provokes another action potential at the next node; this apparent "hopping" of the action potential from node to node is known as
saltatory conduction In neuroscience, saltatory conduction () is the propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials. The uninsulated nodes of Ranvier are th ...
. Although the mechanism of saltatory conduction was suggested in 1925 by Ralph Lillie, See also the first experimental evidence for saltatory conduction came from Ichiji Tasaki and Taiji Takeuchi
*
and from
Andrew Huxley Sir Andrew Fielding Huxley (22 November 191730 May 2012) was an English physiologist and biophysicist. He was born into the prominent Huxley family. After leaving Westminster School in central London, he went to Trinity College, Cambridge ...
and Robert Stämpfli.
*
By contrast, in unmyelinated axons, the action potential provokes another in the membrane immediately adjacent, and moves continuously down the axon like a wave. Myelin has two important advantages: fast conduction speed and energy efficiency. For axons larger than a minimum diameter (roughly 1
micrometre The micrometre ( international spelling as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer (American spelling), also commonly known as a micron, is a unit of length in the International System of Unit ...
), myelination increases the
conduction velocity In neuroscience, nerve conduction velocity (CV) is an important aspect of nerve conduction studies. It is the speed at which an electrochemical impulse propagates down a neural pathway. Conduction velocities are affected by a wide array of factor ...
of an action potential, typically tenfold. Conversely, for a given conduction velocity, myelinated fibers are smaller than their unmyelinated counterparts. For example, action potentials move at roughly the same speed (25 m/s) in a myelinated frog axon and an unmyelinated
squid giant axon The squid giant axon is the very large (up to 1.5 mm in diameter; typically around 0.5 mm) axon that controls part of the water jet propulsion system in squid. It was first described by L. W. Williams in 1909, but this discovery was fo ...
, but the frog axon has a roughly 30-fold smaller diameter and 1000-fold smaller cross-sectional area. Also, since the ionic currents are confined to the nodes of Ranvier, far fewer ions "leak" across the membrane, saving metabolic energy. This saving is a significant selective advantage, since the human nervous system uses approximately 20% of the body's metabolic energy. The length of axons' myelinated segments is important to the success of saltatory conduction. They should be as long as possible to maximize the speed of conduction, but not so long that the arriving signal is too weak to provoke an action potential at the next node of Ranvier. In nature, myelinated segments are generally long enough for the passively propagated signal to travel for at least two nodes while retaining enough amplitude to fire an action potential at the second or third node. Thus, the
safety factor In engineering, a factor of safety (FoS), also known as (and used interchangeably with) safety factor (SF), expresses how much stronger a system is than it needs to be for an intended load. Safety factors are often calculated using detailed analy ...
of saltatory conduction is high, allowing transmission to bypass nodes in case of injury. However, action potentials may end prematurely in certain places where the safety factor is low, even in unmyelinated neurons; a common example is the branch point of an axon, where it divides into two axons. Some diseases degrade myelin and impair saltatory conduction, reducing the conduction velocity of action potentials. The most well-known of these is
multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
, in which the breakdown of myelin impairs coordinated movement.


Cable theory

The flow of currents within an axon can be described quantitatively by
cable theory Classical cable theory uses mathematical models to calculate the electric current (and accompanying voltage) along passive neurites, particularly the dendrites that receive synaptic inputs at different sites and times. Estimates are made by model ...
Rall, W in and its elaborations, such as the compartmental model. Cable theory was developed in 1855 by
Lord Kelvin William Thomson, 1st Baron Kelvin, (26 June 182417 December 1907) was a British mathematician, Mathematical physics, mathematical physicist and engineer born in Belfast. Professor of Natural Philosophy (Glasgow), Professor of Natural Philoso ...
to model the transatlantic telegraph cable and was shown to be relevant to neurons by Hodgkin and Rushton in 1946. In simple cable theory, the neuron is treated as an electrically passive, perfectly cylindrical transmission cable, which can be described by a
partial differential equation In mathematics, a partial differential equation (PDE) is an equation which imposes relations between the various partial derivatives of a Multivariable calculus, multivariable function. The function is often thought of as an "unknown" to be sol ...
: \tau \frac = \lambda^2 \frac - V where ''V''(''x'', ''t'') is the voltage across the membrane at a time ''t'' and a position ''x'' along the length of the neuron, and where λ and τ are the characteristic length and time scales on which those voltages decay in response to a stimulus. Referring to the circuit diagram on the right, these scales can be determined from the resistances and capacitances per unit length. : \tau =\ r_m c_m \, : \lambda = \sqrt \frac These time and length-scales can be used to understand the dependence of the conduction velocity on the diameter of the neuron in unmyelinated fibers. For example, the time-scale τ increases with both the membrane resistance ''rm'' and capacitance ''cm''. As the capacitance increases, more charge must be transferred to produce a given transmembrane voltage (by the equation ''Q'' = ''CV''); as the resistance increases, less charge is transferred per unit time, making the equilibration slower. In a similar manner, if the internal resistance per unit length ''ri'' is lower in one axon than in another (e.g., because the radius of the former is larger), the spatial decay length λ becomes longer and the
conduction velocity In neuroscience, nerve conduction velocity (CV) is an important aspect of nerve conduction studies. It is the speed at which an electrochemical impulse propagates down a neural pathway. Conduction velocities are affected by a wide array of factor ...
of an action potential should increase. If the transmembrane resistance ''rm'' is increased, that lowers the average "leakage" current across the membrane, likewise causing ''λ'' to become longer, increasing the conduction velocity.


Termination


Chemical synapses

In general, action potentials that reach the synaptic knobs cause a
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...
to be released into the synaptic cleft. Neurotransmitters are small molecules that may open ion channels in the postsynaptic cell; most axons have the same neurotransmitter at all of their termini. The arrival of the action potential opens voltage-sensitive calcium channels in the presynaptic membrane; the influx of calcium causes
vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...
filled with neurotransmitter to migrate to the cell's surface and release their contents into the
synaptic cleft Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...
. This complex process is inhibited by the
neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...
s
tetanospasmin Tetanus toxin (TeNT) is an extremely potent neurotoxin produced by the vegetative cell of ''Clostridium tetani'' in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normally ...
and botulinum toxin, which are responsible for
tetanus Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
and
botulism Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium ''Clostridium botulinum''. The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakne ...
, respectively.


Electrical synapses

Some synapses dispense with the "middleman" of the neurotransmitter, and connect the presynaptic and postsynaptic cells together. When an action potential reaches such a synapse, the ionic currents flowing into the presynaptic cell can cross the barrier of the two cell membranes and enter the postsynaptic cell through pores known as
connexon In biology, a connexon, also known as a connexin hemichannel, is an assembly of six proteins called connexins that form the pore for a gap junction between the cytoplasm of two adjacent cells. This channel allows for bidirectional flow of ions and ...
s. Thus, the ionic currents of the presynaptic action potential can directly stimulate the postsynaptic cell. Electrical synapses allow for faster transmission because they do not require the slow diffusion of
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...
s across the synaptic cleft. Hence, electrical synapses are used whenever fast response and coordination of timing are crucial, as in
escape reflex Escape reflex, or escape behavior, is any kind of escape response found in an animal when it is presented with an unwanted stimulus. It is a simple reflectory reaction in response to stimuli indicative of danger, that initiates an escape motion of ...
es, the
retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...
of
vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...
s, and the
heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
.


Neuromuscular junctions

A special case of a chemical synapse is the
neuromuscular junction A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...
, in which the
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...
of a
motor neuron A motor neuron (or motoneuron or efferent neuron) is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectl ...
terminates on a
muscle fiber A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...
. In such cases, the released neurotransmitter is
acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
, which binds to the acetylcholine receptor, an integral membrane protein in the membrane (the ''
sarcolemma The sarcolemma (''sarco'' (from ''sarx'') from Greek; flesh, and ''lemma'' from Greek; sheath) also called the myolemma, is the cell membrane surrounding a skeletal muscle fiber or a cardiomyocyte. It consists of a lipid bilayer and a thin oute ...
'') of the muscle fiber. However, the acetylcholine does not remain bound; rather, it dissociates and is hydrolyzed by the enzyme,
acetylcholinesterase Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme Enzymes () are proteins that a ...
, located in the synapse. This enzyme quickly reduces the stimulus to the muscle, which allows the degree and timing of muscular contraction to be regulated delicately. Some poisons inactivate acetylcholinesterase to prevent this control, such as the
nerve agent Nerve agents, sometimes also called nerve gases, are a class of organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (AChE), an enzyme that ...
s
sarin Sarin (NATO designation GB G-series, "B"">Nerve_agent#G-series.html" ;"title="hort for Nerve agent#G-series">G-series, "B" is an extremely toxic synthetic organophosphorus compound.tabun, and the insecticides
diazinon Diazinon (IUPAC name: ''O'',''O''-Diethyl ''O''- -methyl-6-(propan-2-yl)pyrimidin-2-ylphosphorothioate, INN - Dimpylate), a colorless to dark brown liquid, is a thiophosphoric acid ester developed in 1952 by Ciba-Geigy, a Swiss chemical company ( ...
and malathion.


Other cell types


Cardiac action potentials

The cardiac action potential differs from the neuronal action potential by having an extended plateau, in which the membrane is held at a high voltage for a few hundred milliseconds prior to being repolarized by the potassium current as usual. This plateau is due to the action of slower
calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
channels opening and holding the membrane voltage near their equilibrium potential even after the sodium channels have inactivated. The cardiac action potential plays an important role in coordinating the contraction of the heart. The cardiac cells of the
sinoatrial node The sinoatrial node (also known as the sinuatrial node, SA node or sinus node) is an oval shaped region of special cardiac muscle in the upper back wall of the right atrium made up of cells known as pacemaker cells. The sinus node is approximat ...
provide the
pacemaker potential In the pacemaking cells of the heart (e.g., the sinoatrial node), the pacemaker potential (also called the pacemaker current) is the slow, positive increase in voltage across the cell's membrane (the membrane potential) that occurs between the en ...
that synchronizes the heart. The action potentials of those cells propagate to and through the
atrioventricular node The atrioventricular node or AV node electrically connects the heart's atria and ventricles to coordinate beating in the top of the heart; it is part of the electrical conduction system of the heart. The AV node lies at the lower back section of t ...
(AV node), which is normally the only conduction pathway between the atria and the ventricles. Action potentials from the AV node travel through the
bundle of His The bundle of His (BH) or His bundle (HB) ( "hiss"Medical Terminology for Health Professions, Spiral bound Version'. Cengage Learning; 2016. . pp. 129–.) is a collection of heart muscle cells specialized for electrical conduction. As part of t ...
and thence to the Purkinje fibers.Note that these Purkinje fibers are muscle fibers and not related to the
Purkinje cell Purkinje cells, or Purkinje neurons, are a class of GABAergic inhibitory neurons located in the cerebellum. They are named after their discoverer, Czech people, Czech anatomist Jan Evangelista Purkyně, who characterized the cells in 1839. Stru ...
s, which are
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s found in the
cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...
.
Conversely, anomalies in the cardiac action potential—whether due to a congenital mutation or injury—can lead to human pathologies, especially
arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
s. Several anti-arrhythmia drugs act on the cardiac action potential, such as
quinidine Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of Antimalarial medication, antimalarial agent quinine, originally derived from the bark of the cinchona tre ...
,
lidocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidoca ...
,
beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart ...
s, and
verapamil Verapamil, sold under various trade names, is a calcium channel blocker medication used for the treatment of high blood pressure, angina (chest pain from not enough blood flow to the heart), and supraventricular tachycardia. It may also be ...
.


Muscular action potentials

The action potential in a normal skeletal muscle cell is similar to the action potential in neurons. Action potentials result from the depolarization of the cell membrane (the
sarcolemma The sarcolemma (''sarco'' (from ''sarx'') from Greek; flesh, and ''lemma'' from Greek; sheath) also called the myolemma, is the cell membrane surrounding a skeletal muscle fiber or a cardiomyocyte. It consists of a lipid bilayer and a thin oute ...
), which opens voltage-sensitive sodium channels; these become inactivated and the membrane is repolarized through the outward current of potassium ions. The resting potential prior to the action potential is typically −90mV, somewhat more negative than typical neurons. The muscle action potential lasts roughly 2–4 ms, the absolute refractory period is roughly 1–3 ms, and the conduction velocity along the muscle is roughly 5 m/s. The action potential releases
calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
ions that free up the
tropomyosin Tropomyosin is a two-stranded alpha-helical, coiled coil protein found in actin-based cytoskeletons. Tropomyosin and the actin skeleton All organisms contain organelles that provide physical integrity to their cells. These type of organelles a ...
and allow the muscle to contract. Muscle action potentials are provoked by the arrival of a pre-synaptic neuronal action potential at the
neuromuscular junction A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...
, which is a common target for
neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...
s.


Plant action potentials

Plant Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclud ...
and fungal cells are also electrically excitable. The fundamental difference from animal action potentials is that the depolarization in plant cells is not accomplished by an uptake of positive sodium ions, but by release of negative ''chloride'' ions. In 1906, J. C. Bose published the first measurements of action potentials in plants, which had previously been discovered by Burdon-Sanderson and Darwin. An increase in cytoplasmic calcium ions may be the cause of anion release into the cell. This makes calcium a precursor to ion movements, such as the influx of negative chloride ions and efflux of positive potassium ions, as seen in barley leaves. The initial influx of calcium ions also poses a small cellular depolarization, causing the voltage-gated ion channels to open and allowing full depolarization to be propagated by chloride ions. Some plants (e.g. ''
Dionaea muscipula The Venus flytrap (''Dionaea muscipula'') is a carnivorous plant native to subtropical wetlands on the East Coast of the United States in North Carolina and South Carolina. It catches its prey—chiefly insects and arachnids—with a trapping ...
'') use sodium-gated channels to operate movements and essentially "count". ''Dionaea muscipula'', also known as the Venus flytrap, is found in subtropical wetlands in North and South Carolina. When there are poor soil nutrients, the flytrap relies on a diet of insects and animals. Despite research on the plant, there lacks an understanding behind the molecular basis to the Venus flytraps, and carnivore plants in general. However, plenty of research has been done on action potentials and how they affect movement and clockwork within the Venus flytrap. To start, the resting membrane potential of the Venus flytrap (-120mV) is lower than animal cells (usually -90mV to -40mV). The lower resting potential makes it easier to activate an action potential. Thus, when an insect lands on the trap of the plant, it triggers a hair-like mechanoreceptor. This receptor then activates an action potential which lasts around 1.5 ms. Ultimately, this causes an increase of positive Calcium ions into the cell, slightly depolarizing it. However, the flytrap doesn't close after one trigger. Instead, it requires the activation of 2 or more hairs. If only one hair is triggered, it throws the activation as a false positive. Further, the second hair must be activated within a certain time interval (0.75 s - 40 s) for it to register with the first activation. Thus, a buildup of calcium starts and slowly falls from the first trigger. When the second action potential is fired within the time interval, it reaches the Calcium threshold to depolarize the cell, closing the trap on the prey within a fraction of a second. Together with the subsequent release of positive potassium ions the action potential in plants involves an
osmotic Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region o ...
loss of salt (KCl). Whereas, the animal action potential is osmotically neutral because equal amounts of entering sodium and leaving potassium cancel each other osmotically. The interaction of electrical and osmotic relations in plant cells appears to have arisen from an osmotic function of electrical excitability in a common unicellular ancestors of plants and animals under changing salinity conditions. Further, the present function of rapid signal transmission is seen as a newer accomplishment of
metazoan Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...
cells in a more stable osmotic environment. Gradmann, D; Mummert, H in It is likely that the familiar signaling function of action potentials in some vascular plants (e.g. ''
Mimosa pudica ''Mimosa pudica'' (from la, pudica "shy, bashful or shrinking"; also called sensitive plant, sleepy plant, action plant, touch-me-not, shameplant) is a creeping annual or perennial flowering plant of the pea/legume family Fabaceae. It is often g ...
'') arose independently from that in metazoan excitable cells. Unlike the rising phase and peak, the falling phase and after-hyperpolarization seem to depend primarily on cations that are not calcium. To initiate repolarization, the cell requires movement of potassium out of the cell through passive transportation on the membrane. This differs from neurons because the movement of potassium does not dominate the decrease in membrane potential; In fact, to fully repolarize, a plant cell requires energy in the form of ATP to assist in the release of hydrogen from the cell – utilizing a transporter commonly known as H+-ATPase.Opritov, V A, et al. "Direct Coupling of Action Potential Generation in Cells of a Higher Plant (Cucurbita Pepo) with the Operation of an Electrogenic Pump." ''Russian Journal of Plant Physiology'', vol. 49, no. 1, 2002, pp. 142–147.


Taxonomic distribution and evolutionary advantages

Action potentials are found throughout
multicellular organism A multicellular organism is an organism that consists of more than one cell, in contrast to unicellular organism. All species of animals, land plants and most fungi are multicellular, as are many algae, whereas a few organisms are partially uni- ...
s, including
plant Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclud ...
s,
invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...
s such as
insect Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body ( head, thorax and abdomen), three pairs ...
s, and
vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...
s such as
reptile Reptiles, as most commonly defined are the animals in the class Reptilia ( ), a paraphyletic grouping comprising all sauropsids except birds. Living reptiles comprise turtles, crocodilians, squamates (lizards and snakes) and rhynchocephalians ( ...
s and
mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
s.
Sponge Sponges, the members of the phylum Porifera (; meaning 'pore bearer'), are a basal animal clade as a sister of the diploblasts. They are multicellular organisms that have bodies full of pores and channels allowing water to circulate through t ...
s seem to be the main
phylum In biology, a phylum (; plural: phyla) is a level of classification or taxonomic rank below kingdom and above class. Traditionally, in botany the term division has been used instead of phylum, although the International Code of Nomenclature f ...
of multicellular
eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s that does not transmit action potentials, although some studies have suggested that these organisms have a form of electrical signaling, too. The resting potential, as well as the size and duration of the action potential, have not varied much with evolution, although the
conduction velocity In neuroscience, nerve conduction velocity (CV) is an important aspect of nerve conduction studies. It is the speed at which an electrochemical impulse propagates down a neural pathway. Conduction velocities are affected by a wide array of factor ...
does vary dramatically with axonal diameter and myelination. Given its conservation throughout evolution, the action potential seems to confer evolutionary advantages. One function of action potentials is rapid, long-range signaling within the organism; the conduction velocity can exceed 110 m/s, which is one-third the
speed of sound The speed of sound is the distance travelled per unit of time by a sound wave as it propagates through an elastic medium. At , the speed of sound in air is about , or one kilometre in or one mile in . It depends strongly on temperature as w ...
. For comparison, a hormone molecule carried in the bloodstream moves at roughly 8 m/s in large arteries. Part of this function is the tight coordination of mechanical events, such as the contraction of the heart. A second function is the computation associated with its generation. Being an all-or-none signal that does not decay with transmission distance, the action potential has similar advantages to
digital electronics Digital electronics is a field of electronics involving the study of digital signals and the engineering of devices that use or produce them. This is in contrast to analog electronics and analog signals. Digital electronic circuits are usual ...
. The integration of various dendritic signals at the axon hillock and its thresholding to form a complex train of action potentials is another form of computation, one that has been exploited biologically to form
central pattern generator Central pattern generators (CPGs) are self-organizing biological neural circuits that produce rhythmic outputs in the absence of rhythmic input. They are the source of the tightly-coupled patterns of neural activity that drive rhythmic and stereot ...
s and mimicked in
artificial neural network Artificial neural networks (ANNs), usually simply called neural networks (NNs) or neural nets, are computing systems inspired by the biological neural networks that constitute animal brains. An ANN is based on a collection of connected unit ...
s. The common prokaryotic/eukaryotic ancestor, which lived perhaps four billion years ago, is believed to have had voltage-gated channels. This functionality was likely, at some later point, cross-purposed to provide a communication mechanism. Even modern single-celled bacteria can utilize action potentials to communicate with other bacteria in the same biofilm.


Experimental methods

The study of action potentials has required the development of new experimental methods. The initial work, prior to 1955, was carried out primarily by
Alan Lloyd Hodgkin Sir Alan Lloyd Hodgkin (5 February 1914 – 20 December 1998) was an English physiologist and biophysicist who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles. Early life and education Hodgkin was ...
and
Andrew Fielding Huxley Sir Andrew Fielding Huxley (22 November 191730 May 2012) was an English physiologist and biophysicist. He was born into the prominent Huxley family. After leaving Westminster School in central London, he went to Trinity College, Cambridge on ...
, who were, along
John Carew Eccles Sir John Carew Eccles (27 January 1903 – 2 May 1997) was an Australian neurophysiologist and philosopher who won the 1963 Nobel Prize in Physiology or Medicine for his work on the synapse. He shared the prize with Andrew Huxley and Alan Lloy ...
, awarded the 1963
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
for their contribution to the description of the ionic basis of nerve conduction. It focused on three goals: isolating signals from single neurons or axons, developing fast, sensitive electronics, and shrinking
electrode An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit (e.g. a semiconductor, an electrolyte, a vacuum or air). Electrodes are essential parts of batteries that can consist of a variety of materials de ...
s enough that the voltage inside a single cell could be recorded. The first problem was solved by studying the giant axons found in the neurons of the
squid True squid are molluscs with an elongated soft body, large eyes, eight arms, and two tentacles in the superorder Decapodiformes, though many other molluscs within the broader Neocoleoidea are also called squid despite not strictly fitting t ...
(''
Loligo forbesii ''Loligo forbesii'' (sometimes erroneouslyBouchet, P. and S. Gofas. (2013)''Loligo forbesi'' Steenstrup, 1856.World Register of Marine Species. Accessed 5 June 2013. spelled ''forbesi''), known commonly as the veined squid and long-finned squid, ...
'' and ''
Doryteuthis pealeii The longfin inshore squid (''Doryteuthis pealeii'') is a species of squid of the family Loliginidae. Description This species of squid is often seen with a reddish hue, but like many types of squid can manipulate its color, varying from a deep ...
'', at the time classified as ''Loligo pealeii''). These axons are so large in diameter (roughly 1 mm, or 100-fold larger than a typical neuron) that they can be seen with the naked eye, making them easy to extract and manipulate. However, they are not representative of all excitable cells, and numerous other systems with action potentials have been studied. The second problem was addressed with the crucial development of the
voltage clamp The voltage clamp is an experimental method used by electrophysiologists to measure the ion currents through the membranes of excitable cells, such as neurons, while holding the membrane voltage at a set level. A basic voltage clamp will itera ...
, which permitted experimenters to study the ionic currents underlying an action potential in isolation, and eliminated a key source of
electronic noise In electronics, noise is an unwanted disturbance in an electrical signal. Noise generated by electronic devices varies greatly as it is produced by several different effects. In particular, noise is inherent in physics, and central to the ...
, the current ''IC'' associated with the
capacitance Capacitance is the capability of a material object or device to store electric charge. It is measured by the change in charge in response to a difference in electric potential, expressed as the ratio of those quantities. Commonly recognized are ...
''C'' of the membrane. Since the current equals ''C'' times the rate of change of the transmembrane voltage ''Vm'', the solution was to design a circuit that kept ''Vm'' fixed (zero rate of change) regardless of the currents flowing across the membrane. Thus, the current required to keep ''Vm'' at a fixed value is a direct reflection of the current flowing through the membrane. Other electronic advances included the use of Faraday cages and electronics with high
input impedance The input impedance of an electrical network is the measure of the opposition to current ( impedance), both static ( resistance) and dynamic ( reactance), into the load network that is ''external'' to the electrical source. The input admittance (the ...
, so that the measurement itself did not affect the voltage being measured. The third problem, that of obtaining electrodes small enough to record voltages within a single axon without perturbing it, was solved in 1949 with the invention of the glass micropipette electrode, which was quickly adopted by other researchers. Refinements of this method are able to produce electrode tips that are as fine as 100 Å (10 nm), which also confers high input impedance. Action potentials may also be recorded with small metal electrodes placed just next to a neuron, with
neurochip A neurochip is an integrated circuit chip (such as a microprocessor) that is designed for interaction with neuronal cells. Formation It is made of silicon that is doped in such a way that it contains EOSFETs (electrolyte- oxide-semiconductor ...
s containing
EOSFET An EOSFET or electrolyte–oxide–semiconductor field-effect transistor is a FET, like a MOSFET, but with an electrolyte solution replacing the metal for the detection of neuron A neuron, neurone, or nerve cell is an electrically excitabl ...
s, or optically with dyes that are sensitive to Ca2+ or to voltage.
*
While glass micropipette electrodes measure the sum of the currents passing through many ion channels, studying the electrical properties of a single ion channel became possible in the 1970s with the development of the
patch clamp The patch clamp technique is a laboratory technique in electrophysiology used to study ionic currents in individual isolated living cells, tissue sections, or patches of cell membrane. The technique is especially useful in the study of excitabl ...
by
Erwin Neher Erwin Neher (; ; born 20 March 1944) is a German biophysicist, specializing in the field of cell physiology. For significant contribution in the field, in 1991 he was awarded, along with Bert Sakmann, the Nobel Prize in Physiology or Medicine for ...
and
Bert Sakmann Bert Sakmann (; born 12 June 1942) is a German cell physiologist. He shared the Nobel Prize in Physiology or Medicine with Erwin Neher in 1991 for their work on "the function of single ion channels in cells," and the invention of the patch cla ...
. For this discovery, they were awarded the
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
in 1991. Patch-clamping verified that ionic channels have discrete states of conductance, such as open, closed and inactivated.
Optical imaging Medical optical imaging is the use of light as an investigational :wikt:imaging, imaging technique for medical applications. Examples include optical microscopy, spectroscopy, endoscopy, scanning laser ophthalmoscopy, laser Doppler imaging, and opti ...
technologies have been developed in recent years to measure action potentials, either via simultaneous multisite recordings or with ultra-spatial resolution. Using voltage-sensitive dyes, action potentials have been optically recorded from a tiny patch of
cardiomyocyte Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...
membrane.


Neurotoxins

Several
neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...
s, both natural and synthetic, are designed to block the action potential.
Tetrodotoxin Tetrodotoxin (TTX) is a potent neurotoxin. Its name derives from Tetraodontiformes, an order that includes pufferfish, porcupinefish, ocean sunfish, and triggerfish; several of these species carry the toxin. Although tetrodotoxin was discovered ...
from the pufferfish and
saxitoxin Saxitoxin (STX) is a potent neurotoxin and the best-known paralytic shellfish toxin (PST). Ingestion of saxitoxin by humans, usually by consumption of shellfish contaminated by toxic algal blooms, is responsible for the illness known as paralyt ...
from the ''
Gonyaulax ''Gonyaulax'' is a genus of dinoflagellates with the type species ''Gonyaulax spinifera'' (Claparède et Lachmann) Diesing. ''Gonyaulax'' belongs to red dinoflagellates and commonly causes red tides. It secretes a poisonous toxin known as "saxit ...
'' (the
dinoflagellate The dinoflagellates (Greek δῖνος ''dinos'' "whirling" and Latin ''flagellum'' "whip, scourge") are a monophyletic group of single-celled eukaryotes constituting the phylum Dinoflagellata and are usually considered algae. Dinoflagellates are ...
genus responsible for "
red tide A harmful algal bloom (HAB) (or excessive algae growth) is an algal bloom that causes negative impacts to other organisms by production of natural phycotoxin, algae-produced toxins, mechanical damage to other organisms, or by other means. HABs are ...
s") block action potentials by inhibiting the voltage-sensitive sodium channel;
*
*
similarly,
dendrotoxin Dendrotoxins are a class of presynaptic neurotoxins produced by mamba snakes ('' Dendroaspis'') that block particular subtypes of voltage-gated potassium channels in neurons, thereby enhancing the release of acetylcholine at neuromuscular junctio ...
from the black mamba snake inhibits the voltage-sensitive potassium channel. Such inhibitors of ion channels serve an important research purpose, by allowing scientists to "turn off" specific channels at will, thus isolating the other channels' contributions; they can also be useful in purifying ion channels by
affinity chromatography Affinity chromatography is a method of separating a biomolecule from a mixture, based on a highly specific macromolecular binding interaction between the biomolecule and another substance. The specific type of binding interaction depends on the ...
or in assaying their concentration. However, such inhibitors also make effective neurotoxins, and have been considered for use as
chemical weapon A chemical weapon (CW) is a specialized munition that uses chemicals formulated to inflict death or harm on humans. According to the Organisation for the Prohibition of Chemical Weapons (OPCW), this can be any chemical compound intended as a ...
s. Neurotoxins aimed at the ion channels of insects have been effective
insecticide Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed to b ...
s; one example is the synthetic
permethrin Permethrin is a medication and an insecticide. As a medication, it is used to treat scabies and lice. It is applied to the skin as a cream or lotion. As an insecticide, it can be sprayed onto clothing or mosquito nets to kill the insects th ...
, which prolongs the activation of the sodium channels involved in action potentials. The ion channels of insects are sufficiently different from their human counterparts that there are few side effects in humans.


History

The role of electricity in the nervous systems of animals was first observed in dissected
frog A frog is any member of a diverse and largely Carnivore, carnivorous group of short-bodied, tailless amphibians composing the order (biology), order Anura (ανοὐρά, literally ''without tail'' in Ancient Greek). The oldest fossil "proto-f ...
s by Luigi Galvani, who studied it from 1791 to 1797. Galvani's results stimulated
Alessandro Volta Alessandro Giuseppe Antonio Anastasio Volta (, ; 18 February 1745 – 5 March 1827) was an Italian physicist, chemist and lay Catholic who was a pioneer of electricity and power who is credited as the inventor of the electric battery and the ...
to develop the
Voltaic pile upright=1.2, Schematic diagram of a copper–zinc voltaic pile. The copper and zinc discs were separated by cardboard or felt spacers soaked in salt water (the electrolyte). Volta's original piles contained an additional zinc disk at the bottom, ...
—the earliest-known
electric battery An electric battery is a source of electric power consisting of one or more electrochemical cells with external connections for powering electrical devices. When a battery is supplying power, its positive terminal is the cathode and its negati ...
—with which he studied animal electricity (such as
electric eel The electric eels are a genus, ''Electrophorus'', of neotropical freshwater fish from South America in the family Gymnotidae. They are known for their ability to stun their prey by generating electricity, delivering shocks at up to 860 volt ...
s) and the physiological responses to applied
direct-current Direct current (DC) is one-directional flow of electric charge. An electrochemical cell is a prime example of DC power. Direct current may flow through a conductor such as a wire, but can also flow through semiconductors, insulators, or even ...
voltage Voltage, also known as electric pressure, electric tension, or (electric) potential difference, is the difference in electric potential between two points. In a static electric field, it corresponds to the work needed per unit of charge to m ...
s. Scientists of the 19th century studied the propagation of electrical signals in whole
nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
s (i.e., bundles of
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s) and demonstrated that nervous tissue was made up of cells, instead of an interconnected network of tubes (a ''reticulum'').
Carlo Matteucci Carlo Matteucci (20 or 21 June 1811 – 25 June 1868) was an Italian physicist and neurophysiologist who was a pioneer in the study of bioelectricity. Biography Carlo Matteucci was born at Forlì, in the province of Romagna, to Vincenzo Matt ...
followed up Galvani's studies and demonstrated that
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
s had a voltage across them and could produce
direct current Direct current (DC) is one-directional flow of electric charge. An electrochemical cell is a prime example of DC power. Direct current may flow through a conductor such as a wire, but can also flow through semiconductors, insulators, or even ...
. Matteucci's work inspired the German physiologist,
Emil du Bois-Reymond Emil Heinrich du Bois-Reymond (7 November 181826 December 1896) was a German physician and physiologist, the co-discoverer of nerve action potential, and the developer of experimental electrophysiology. Life Du Bois-Reymond was born in Berlin a ...
, who discovered the action potential in 1843. The
conduction velocity In neuroscience, nerve conduction velocity (CV) is an important aspect of nerve conduction studies. It is the speed at which an electrochemical impulse propagates down a neural pathway. Conduction velocities are affected by a wide array of factor ...
of action potentials was first measured in 1850 by du Bois-Reymond's friend,
Hermann von Helmholtz Hermann Ludwig Ferdinand von Helmholtz (31 August 1821 – 8 September 1894) was a German physicist and physician who made significant contributions in several scientific fields, particularly hydrodynamic stability. The Helmholtz Association, ...
. To establish that nervous tissue is made up of discrete cells, the Spanish physician
Santiago Ramón y Cajal Santiago Ramón y Cajal (; 1 May 1852 – 17 October 1934) was a Spanish neuroscientist, pathologist, and histologist specializing in neuroanatomy and the central nervous system. He and Camillo Golgi received the Nobel Prize in Physiology or Med ...
and his students used a stain developed by
Camillo Golgi Camillo Golgi (; 7 July 184321 January 1926) was an Italian biologist and pathologist known for his works on the central nervous system. He studied medicine at the University of Pavia (where he later spent most of his professional career) betwee ...
to reveal the myriad shapes of neurons, which they rendered painstakingly. For their discoveries, Golgi and Ramón y Cajal were awarded the 1906
Nobel Prize in Physiology The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, according ...
. Their work resolved a long-standing controversy in the
neuroanatomy Neuroanatomy is the study of the structure and organization of the nervous system. In contrast to animals with radial symmetry, whose nervous system consists of a distributed network of cells, animals with bilateral symmetry have segregated, defin ...
of the 19th century; Golgi himself had argued for the network model of the nervous system. The 20th century was a significant era for electrophysiology. In 1902 and again in 1912,
Julius Bernstein Julius Bernstein (18 December 1839 – 6 February 1917) was a German physiologist born in Berlin. His father was Aron Bernstein (1812—1884), a founder of the Reform Judaism Congregation in Berlin 1845; his son was the mathematician Felix ...
advanced the hypothesis that the action potential resulted from a change in the permeability of the axonal membrane to ions. Bernstein's hypothesis was confirmed by Ken Cole and Howard Curtis, who showed that membrane conductance increases during an action potential. In 1907, Louis Lapicque suggested that the action potential was generated as a threshold was crossed, what would be later shown as a product of the
dynamical system In mathematics, a dynamical system is a system in which a Function (mathematics), function describes the time dependence of a Point (geometry), point in an ambient space. Examples include the mathematical models that describe the swinging of a ...
s of ionic conductances. In 1949,
Alan Hodgkin Sir Alan Lloyd Hodgkin (5 February 1914 – 20 December 1998) was an English physiologist and biophysicist who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles. Early life and education Hodgkin was bo ...
and Bernard Katz refined Bernstein's hypothesis by considering that the axonal membrane might have different permeabilities to different ions; in particular, they demonstrated the crucial role of the sodium permeability for the action potential. They made the first actual recording of the electrical changes across the neuronal membrane that mediate the action potential. This line of research culminated in the five 1952 papers of Hodgkin, Katz and
Andrew Huxley Sir Andrew Fielding Huxley (22 November 191730 May 2012) was an English physiologist and biophysicist. He was born into the prominent Huxley family. After leaving Westminster School in central London, he went to Trinity College, Cambridge ...
, in which they applied the
voltage clamp The voltage clamp is an experimental method used by electrophysiologists to measure the ion currents through the membranes of excitable cells, such as neurons, while holding the membrane voltage at a set level. A basic voltage clamp will itera ...
technique to determine the dependence of the axonal membrane's permeabilities to sodium and potassium ions on voltage and time, from which they were able to reconstruct the action potential quantitatively.
*
*
*
*
Hodgkin and Huxley correlated the properties of their mathematical model with discrete
ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
s that could exist in several different states, including "open", "closed", and "inactivated". Their hypotheses were confirmed in the mid-1970s and 1980s by
Erwin Neher Erwin Neher (; ; born 20 March 1944) is a German biophysicist, specializing in the field of cell physiology. For significant contribution in the field, in 1991 he was awarded, along with Bert Sakmann, the Nobel Prize in Physiology or Medicine for ...
and
Bert Sakmann Bert Sakmann (; born 12 June 1942) is a German cell physiologist. He shared the Nobel Prize in Physiology or Medicine with Erwin Neher in 1991 for their work on "the function of single ion channels in cells," and the invention of the patch cla ...
, who developed the technique of
patch clamp The patch clamp technique is a laboratory technique in electrophysiology used to study ionic currents in individual isolated living cells, tissue sections, or patches of cell membrane. The technique is especially useful in the study of excitabl ...
ing to examine the conductance states of individual ion channels.
*
*
In the 21st century, researchers are beginning to understand the structural basis for these conductance states and for the selectivity of channels for their species of ion, through the atomic-resolution
crystal structures A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macrosc ...
,
*
*
fluorescence distance measurements
*
*
and
cryo-electron microscopy Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample s ...
studies.
*
Julius Bernstein was also the first to introduce the
Nernst equation In electrochemistry, the Nernst equation is a chemical thermodynamical relationship that permits the calculation of the reduction potential of a reaction ( half-cell or full cell reaction) from the standard electrode potential, absolute tempe ...
for
resting potential A relatively static membrane potential which is usually referred to as the ground value for trans-membrane voltage. The relatively static membrane potential of quiescent cells is called the resting membrane potential (or resting voltage), as opp ...
across the membrane; this was generalized by David E. Goldman to the eponymous
Goldman equation The Goldman–Hodgkin–Katz voltage equation, more commonly known as the Goldman equation, is used in cell membrane physiology to determine the reversal potential across a cell's membrane, taking into account all of the ions that are permeant t ...
in 1943. The
sodium–potassium pump The sodium–potassium pump (sodium–potassium adenosine triphosphatase, also known as Na⁺/K⁺-ATPase, Na⁺/K⁺ pump, or sodium–potassium ATPase) is an enzyme (an electrogenic transmembrane ATPase) found in the membrane of all animal c ...
was identified in 1957 and its properties gradually elucidated, culminating in the determination of its atomic-resolution structure by
X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
. The crystal structures of related ionic pumps have also been solved, giving a broader view of how these molecular machines work.


Quantitative models

Mathematical and computational models are essential for understanding the action potential, and offer predictions that may be tested against experimental data, providing a stringent test of a theory. The most important and accurate of the early neural models is the
Hodgkin–Huxley model The Hodgkin–Huxley model, or conductance-based model, is a mathematical model that describes how action potentials in neurons are initiated and propagated. It is a set of nonlinear differential equations that approximates the electrical charact ...
, which describes the action potential by a coupled set of four
ordinary differential equation In mathematics, an ordinary differential equation (ODE) is a differential equation whose unknown(s) consists of one (or more) function(s) of one variable and involves the derivatives of those functions. The term ''ordinary'' is used in contrast w ...
s (ODEs). Although the Hodgkin–Huxley model may be a simplification with few limitations compared to the realistic nervous membrane as it exists in nature, its complexity has inspired several even-more-simplified models,*
*
such as the Morris–Lecar model and the
FitzHugh–Nagumo model The FitzHugh–Nagumo model (FHN), named after Richard FitzHugh (1922–2007) who suggested the system in 1961 and J. Nagumo ''et al''. who created the equivalent circuit the following year, describes a prototype of an excitable system (e.g., a n ...
,
*
both of which have only two coupled ODEs. The properties of the Hodgkin–Huxley and FitzHugh–Nagumo models and their relatives, such as the Bonhoeffer–Van der Pol model,
*
*
*
*
have been well-studied within mathematics,Sato, S; Fukai, H; Nomura, T; Doi, S in
* FitzHugh, R in
*

*
computationNelson, ME; Rinzel, J in
* Rinzel, J & Ermentrout, GB; in
and electronics. However the simple models of generator potential and action potential fail to accurately reproduce the near threshold neural spike rate and spike shape, specifically for the mechanoreceptors like the
Pacinian corpuscle Pacinian corpuscle or lamellar corpuscle or Vater-Pacini corpuscle; is one of the four major types of mechanoreceptors (specialized nerve ending with adventitious tissue for mechanical sensation) found in mammalian skin. This type of mechanorece ...
. More modern research has focused on larger and more integrated systems; by joining action-potential models with models of other parts of the nervous system (such as dendrites and synapses), researchers can study
neural computation Neural computation is the information processing performed by networks of neurons. Neural computation is affiliated with the philosophical tradition known as Computational theory of mind, also referred to as computationalism, which advances the th ...
and simple
reflex In biology, a reflex, or reflex action, is an involuntary, unplanned sequence or action and nearly instantaneous response to a stimulus. Reflexes are found with varying levels of complexity in organisms with a nervous system. A reflex occurs ...
es, such as
escape reflex Escape reflex, or escape behavior, is any kind of escape response found in an animal when it is presented with an unwanted stimulus. It is a simple reflectory reaction in response to stimuli indicative of danger, that initiates an escape motion of ...
es and others controlled by
central pattern generator Central pattern generators (CPGs) are self-organizing biological neural circuits that produce rhythmic outputs in the absence of rhythmic input. They are the source of the tightly-coupled patterns of neural activity that drive rhythmic and stereot ...
s.Getting, PA in


See also

*
Anode break excitation Anode break excitation (ABE) is an electrophysiological phenomenon whereby a neuron fires action potentials in response to termination of a Hyperpolarization (biology), hyperpolarizing current. When a hyperpolarizing current is applied across a me ...
*
Bioelectricity In developmental biology, bioelectricity refers to the regulation of cell, tissue, and organ-level patterning and behavior as the result of endogenous electrically mediated signaling. Cells and tissues of all types use ion fluxes to communicate e ...
*
Biological neuron model Biological neuron models, also known as a spiking neuron models, are mathematical descriptions of the properties of certain cells in the nervous system that generate sharp electrical potentials across their cell membrane, roughly one millisecon ...
* Bursting *
Central pattern generator Central pattern generators (CPGs) are self-organizing biological neural circuits that produce rhythmic outputs in the absence of rhythmic input. They are the source of the tightly-coupled patterns of neural activity that drive rhythmic and stereot ...
* Chronaxie * Frog battery * Law of specific nerve energies *
Neural accommodation Neural accommodation or neuronal accommodation occurs when a neuron or muscle cell is depolarised by slowly rising current ( ramp depolarisation) ''in vitro''. The Hodgkin–Huxley model also shows accommodation. Sudden depolarisation of a nerve ...
*
Single-unit recording In neuroscience, single-unit recordings provide a method of measuring the electro-physiological responses of a single neuron using a microelectrode system. When a neuron generates an action potential, the signal propagates down the neuron as a cu ...
*
Soliton model in neuroscience The soliton hypothesis in neuroscience is a model that claims to explain how action potentials are initiated and conducted along axons based on a thermodynamic theory of nerve pulse propagation. It proposes that the signals travel along the cel ...


Notes


References


Footnotes


Journal articles


Books

* * * * * * * * * * * * * * * * * * * * * * * * * * *


Web pages


Further reading

* * * * * * * * *


External links


Ionic flow in action potentials
at
Blackwell Publishing Wiley-Blackwell is an international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons. It was formed by the merger of John Wiley & Sons Global Scientific, Technical, and Medical business with Blackwell Publish ...

Action potential propagation in myelinated and unmyelinated axons
at
Blackwell Publishing Wiley-Blackwell is an international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons. It was formed by the merger of John Wiley & Sons Global Scientific, Technical, and Medical business with Blackwell Publish ...

Generation of AP in cardiac cells
an



from ''Life: The Science of Biology'', by WK Purves, D Sadava, GH Orians, and HC Heller, 8th edition, New York: WH Freeman, .
Ionic motion and the Goldman voltage for arbitrary ionic concentrations
at The
University of Arizona The University of Arizona (Arizona, U of A, UArizona, or UA) is a public land-grant research university in Tucson, Arizona. Founded in 1885 by the 13th Arizona Territorial Legislature, it was the first university in the Arizona Territory. T ...

A cartoon illustrating the action potential

Action potential propagation

Production of the action potential: voltage and current clamping simulations

Open-source software to simulate neuronal and cardiac action potentials
at
SourceForge.net SourceForge is a web service that offers software consumers a centralized online location to control and manage open-source software projects and research business software. It provides source code repository hosting, bug tracking, mirroring ...

Introduction to the Action Potential
''Neuroscience Online'' (electronic neuroscience textbook by UT Houston Medical School)
Khan Academy: Electrotonic and action potential
{{DEFAULTSORT:Action Potential Capacitors Neural coding Electrophysiology Electrochemistry Computational neuroscience Cellular neuroscience Cellular processes Membrane biology Plant cognition Action potentials