![Basis of Membrane Potential2](https://upload.wikimedia.org/wikipedia/commons/f/fb/Basis_of_Membrane_Potential2.png)
Membrane potential (also transmembrane potential or membrane voltage) is the difference in
electric potential
The electric potential (also called the ''electric field potential'', potential drop, the electrostatic potential) is defined as the amount of work energy needed to move a unit of electric charge from a reference point to the specific point in ...
between the interior and the exterior of a biological
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 w ...
. That is, there is a difference in the energy required for electric charges to move from the internal to exterior cellular environments and vice versa, as long as there is no acquisition of kinetic energy or the production of radiation. The concentration gradients of the charges directly determine this energy requirement. For the exterior of the cell, typical values of membrane potential, normally given in units of
milli
''Milli'' (symbol m) is a unit prefix in the metric system denoting a factor of one thousandth (10−3). Proposed in 1793, and adopted in 1795, the prefix comes from the Latin , meaning ''one thousand'' (the Latin plural is ). Since 1960, the pre ...
volt
The volt (symbol: V) is the unit of electric potential, electric potential difference (voltage), and electromotive force in the International System of Units (SI). It is named after the Italian physicist Alessandro Volta (1745–1827).
Defi ...
s and denoted as mV, range from –80 mV to –40 mV.
All animal cells are surrounded by a
membrane
A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
composed 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 ...
with
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s embedded in it. The membrane serves as both an insulator and a diffusion barrier to the movement of
ion
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 conven ...
s.
Transmembrane proteins
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...
, also known as
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 produc ...
or
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 ...
proteins, actively push ions across the membrane and establish concentration gradients across the membrane, 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 allow ions to move across the membrane down those concentration gradients. Ion pumps and ion channels are electrically equivalent to a set of
batteries
Battery most often refers to:
* Electric battery, a device that provides electrical power
* Battery (crime), a crime involving unlawful physical contact
Battery may also refer to:
Energy source
*Automotive battery, a device to provide power t ...
and resistors inserted in the membrane, and therefore create a voltage between the two sides of the membrane.
Almost all plasma membranes have an electrical potential across them, with the inside usually negative with respect to the outside. The membrane potential has two basic functions. First, it allows a cell to function as a battery, providing power to operate a variety of "molecular devices" embedded in the membrane. Second, in electrically excitable cells such as
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
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 muscle ...
, it is used for transmitting signals between different parts of a cell. Signals are generated by opening or closing of ion channels at one point in the membrane, producing a local change in the membrane potential. This change in the electric field can be quickly sensed by either adjacent or more distant ion channels in the membrane. Those ion channels can then open or close as a result of the potential change, reproducing the signal.
In non-excitable cells, and in excitable cells in their baseline states, the membrane potential is held at a relatively stable value, called 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 oppo ...
. For neurons, resting potential is defined as ranging from –80 to –70 millivolts; that is, the interior of a cell has a negative baseline voltage of a bit less than one-tenth of a volt. The opening and closing of ion channels can induce a departure from the resting potential. This is called a
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 esse ...
if the interior voltage becomes less negative (say from –70 mV to –60 mV), or a
hyperpolarization if the interior voltage becomes more negative (say from –70 mV to –80 mV). In excitable cells, a sufficiently large depolarization can evoke an
action potential
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
, in which the membrane potential changes rapidly and significantly for a short time (on the order of 1 to 100 milliseconds), often reversing its polarity. Action potentials are generated by the activation of certain
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.
In neurons, the factors that influence the membrane potential are diverse. They include numerous types of ion channels, some of which are chemically gated and some of which are voltage-gated. Because voltage-gated ion channels are controlled by the membrane potential, while the membrane potential itself is influenced by these same ion channels, feedback loops that allow for complex temporal dynamics arise, including oscillations and regenerative events such as action potentials.
Physical basis
The membrane potential in a cell derives ultimately from two factors: electrical force and diffusion. Electrical force arises from the mutual attraction between particles with opposite electrical charges (positive and negative) and the mutual repulsion between particles with the same type of charge (both positive or both negative). Diffusion arises from the statistical tendency of particles to redistribute from regions where they are highly concentrated to regions where the concentration is low.
Voltage
![Electric dipole](https://upload.wikimedia.org/wikipedia/commons/7/76/Electric_dipole.PNG)
Voltage, which is synonymous with ''difference in electrical potential'', is the ability to drive an electric current across a resistance. Indeed, the simplest definition of a voltage is given by
Ohm's law
Ohm's law states that the current through a conductor between two points is directly proportional to the voltage across the two points. Introducing the constant of proportionality, the resistance, one arrives at the usual mathematical equat ...
: V=IR, where V is voltage, I is current and R is resistance. If a voltage source such as a battery is placed in an electrical circuit, the higher the voltage of the source the greater the amount of current that it will drive across the available resistance. The functional significance of voltage lies only in potential ''differences'' between two points in a circuit. The idea of a voltage at a single point is meaningless. It is conventional in electronics to assign a voltage of zero to some arbitrarily chosen element of the circuit, and then assign voltages for other elements measured relative to that zero point. There is no significance in which element is chosen as the zero point—the function of a circuit depends only on the differences not on voltages ''per se''. However, in most cases and by convention, the zero level is most often assigned to the portion of a circuit that is in contact with
ground.
The same principle applies to voltage in cell biology. In electrically active tissue, the potential difference between any two points can be measured by inserting an electrode at each point, for example one inside and one outside the cell, and connecting both electrodes to the leads of what is in essence a specialized voltmeter. By convention, the zero potential value is assigned to the outside of the cell and the sign of the potential difference between the outside and the inside is determined by the potential of the inside relative to the outside zero.
In mathematical terms, the definition of voltage begins with the concept of an
electric field
An electric field (sometimes E-field) is the physical field that surrounds electrically charged particles and exerts force on all other charged particles in the field, either attracting or repelling them. It also refers to the physical field fo ...
, a vector field assigning a magnitude and direction to each point in space. In many situations, the electric field is a
conservative field
In vector calculus, a conservative vector field is a vector field that is the gradient of some function. A conservative vector field has the property that its line integral is path independent; the choice of any path between two points does not c ...
, which means that it can be expressed as the
gradient
In vector calculus, the gradient of a scalar-valued differentiable function of several variables is the vector field (or vector-valued function) \nabla f whose value at a point p is the "direction and rate of fastest increase". If the gradi ...
of a scalar function , that is, . This scalar field is referred to as the voltage distribution. Note that the definition allows for an arbitrary constant of integration—this is why absolute values of voltage are not meaningful. In general, electric fields can be treated as conservative only if magnetic fields do not significantly influence them, but this condition usually applies well to biological tissue.
Because the electric field is the gradient of the voltage distribution, rapid changes in voltage within a small region imply a strong electric field; on the converse, if the voltage remains approximately the same over a large region, the electric fields in that region must be weak. A strong electric field, equivalent to a strong voltage gradient, implies that a strong force is exerted on any charged particles that lie within the region.
Ions and the forces driving their motion
![Diffusion](https://upload.wikimedia.org/wikipedia/commons/7/72/Diffusion.en.svg)
Electrical signals within biological organisms are, in general, driven by
ion
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 conven ...
s. The most important cations for the action potential are
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 ...
(Na
+) and
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 ...
(K
+).
Bullock
Bullock may refer to:
Animals
* Bullock (in British English), a castrated male bovine animal of any age
* Bullock (in North America), a young bull (an uncastrated male bovine animal)
* Bullock (in Australia, India and New Zealand), an ox, an adu ...
, Orkand, and Grinnell, pp. 140–41. Both of these are ''monovalent'' cations that carry a single positive charge. Action potentials can also involve
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 ...
(Ca
2+), which is a ''divalent'' cation that carries a double positive charge. The
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 (Cl
−) plays a major role in the action potentials of some
algae
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 mic ...
,
but plays a negligible role in the action potentials of most animals.
Ions cross the cell membrane under two influences:
diffusion
Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
and
electric field
An electric field (sometimes E-field) is the physical field that surrounds electrically charged particles and exerts force on all other charged particles in the field, either attracting or repelling them. It also refers to the physical field fo ...
s. A simple example wherein two solutions—A and B—are separated by a porous barrier illustrates that diffusion will ensure that they will eventually mix into equal solutions. This mixing occurs because of the difference in their concentrations. The region with high concentration will diffuse out toward the region with low concentration. To extend the example, let solution A have 30 sodium ions and 30 chloride ions. Also, let solution B have only 20 sodium ions and 20 chloride ions. Assuming the barrier allows both types of ions to travel through it, then a steady state will be reached whereby both solutions have 25 sodium ions and 25 chloride ions. If, however, the porous barrier is selective to which ions are let through, then diffusion alone will not determine the resulting solution. Returning to the previous example, let's now construct a barrier that is permeable only to sodium ions. Now, only sodium is allowed to diffuse cross the barrier from its higher concentration in solution A to the lower concentration in solution B. This will result in a greater accumulation of sodium ions than chloride ions in solution B and a lesser number of sodium ions than chloride ions in solution A.
This means that there is a net positive charge in solution B from the higher concentration of positively charged sodium ions than negatively charged chloride ions. Likewise, there is a net negative charge in solution A from the greater concentration of negative chloride ions than positive sodium ions. Since opposite charges attract and like charges repel, the ions are now also influenced by electrical fields as well as forces of diffusion. Therefore, positive sodium ions will be less likely to travel to the now-more-positive B solution and remain in the now-more-negative A solution. The point at which the forces of the electric fields completely counteract the force due to diffusion is called the equilibrium potential. At this point, the net flow of the specific ion (in this case sodium) is zero.
Plasma membranes
![Cell membrane detailed diagram en](https://upload.wikimedia.org/wikipedia/commons/d/da/Cell_membrane_detailed_diagram_en.svg)
Every cell is enclosed in a
plasma 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 (t ...
, which has the structure 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 ...
with many types of large molecules embedded in it. Because it is made of lipid molecules, the plasma membrane intrinsically has a high electrical resistivity, in other words a low intrinsic permeability to ions. However, some of the molecules embedded in the membrane are capable either of actively transporting ions from one side of the membrane to the other or of providing channels through which they can move.
In electrical terminology, the plasma membrane functions as a combined
resistor
A resistor is a passive two-terminal electrical component that implements electrical resistance as a circuit element. In electronic circuits, resistors are used to reduce current flow, adjust signal levels, to divide voltages, bias active el ...
and
capacitor
A capacitor is a device that stores electrical energy in an electric field by virtue of accumulating electric charges on two close surfaces insulated from each other. It is a passive electronic component with two terminals.
The effect of ...
. Resistance arises from the fact that the membrane impedes the movement of charges across it. Capacitance arises from the fact that the lipid bilayer is so thin that an accumulation of charged particles on one side gives rise to an electrical force that pulls oppositely charged particles toward the other side. The capacitance of the membrane is relatively unaffected by the molecules that are embedded in it, so it has a more or less invariant value estimated at 2 μF/cm
2 (the total capacitance of a patch of membrane is proportional to its area). The conductance of a pure lipid bilayer is so low, on the other hand, that in biological situations it is always dominated by the conductance of alternative pathways provided by embedded molecules. Thus, the capacitance of the membrane is more or less fixed, but the resistance is highly variable.
The thickness of a plasma membrane is estimated to be about 7-8 nanometers. Because the membrane is so thin, it does not take a very large transmembrane voltage to create a strong electric field within it. Typical membrane potentials in animal cells are on the order of 100 millivolts (that is, one tenth of a volt), but calculations show that this generates an electric field close to the maximum that the membrane can sustain—it has been calculated that a voltage difference much larger than 200 millivolts could cause
dielectric breakdown
Electrical breakdown or dielectric breakdown is a process that occurs when an electrical insulating material, subjected to a high enough voltage, suddenly becomes an electrical conductor and electric current flows through it. All insulating mate ...
, that is, arcing across the membrane.
Facilitated diffusion and transport
![Scheme facilitated diffusion in cell membrane-en](https://upload.wikimedia.org/wikipedia/commons/9/91/Scheme_facilitated_diffusion_in_cell_membrane-en.svg)
The resistance of a pure lipid bilayer to the passage of ions across it is very high, but structures embedded in the membrane can greatly enhance ion movement, either
actively or
passively, via mechanisms called
facilitated transport
Facilitated diffusion (also known as facilitated transport or passive-mediated transport) is the process of spontaneous passive transport (as opposed to active transport) of molecules or ions across a biological membrane via specific transmembra ...
and
facilitated diffusion
Facilitated diffusion (also known as facilitated transport or passive-mediated transport) is the process of spontaneous passive transport (as opposed to active transport) of molecules or ions across a biological membrane via specific transmembra ...
. The two types of structure that play the largest roles are ion channels and
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, both usually formed from assemblages of protein molecules. Ion channels provide passageways through which ions can move. In most cases, an ion channel is permeable only to specific types of ions (for example, sodium and potassium but not chloride or calcium), and sometimes the permeability varies depending on the direction of ion movement. Ion pumps, also known as ion transporters or carrier proteins, actively transport specific types of ions from one side of the membrane to the other, sometimes using energy derived from metabolic processes to do so.
Ion pumps
Ion pumps
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 ...
are
integral membrane protein
An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a signi ...
s that carry out
active transport
In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...
, i.e., use cellular energy (ATP) to "pump" the ions against their concentration gradient.
Such ion pumps take in ions from one side of the membrane (decreasing its concentration there) and release them on the other side (increasing its concentration there).
The ion pump most relevant to the action potential is 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 transports three sodium ions out of the cell and two potassium ions in.
As a consequence, the concentration 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 K
+ inside the neuron is roughly 20-fold larger than the outside concentration, whereas the sodium concentration outside is roughly ninefold larger than inside.
In a similar manner, other ions have different concentrations inside and outside the neuron, such as
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 ...
,
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 ...
and
magnesium
Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...
.
If the numbers of each type of ion were equal, the sodium–potassium pump would be electrically neutral, but, because of the three-for-two exchange, it gives a net movement of one positive charge from intracellular to extracellular for each cycle, thereby contributing to a positive voltage difference. The pump has three effects: (1) it makes the sodium concentration high in the extracellular space and low in the intracellular space; (2) it makes the potassium concentration high in the intracellular space and low in the extracellular space; (3) it gives the intracellular space a negative voltage with respect to the extracellular space.
The sodium-potassium pump is relatively slow in operation. If a cell were initialized with equal concentrations of sodium and potassium everywhere, it would take hours for the pump to establish equilibrium. The pump operates constantly, but becomes progressively less efficient as the concentrations of sodium and potassium available for pumping are reduced.
Ion pumps influence the action potential only by establishing the relative ratio of intracellular and extracellular ion concentrations. The action potential involves mainly the opening and closing of ion channels not ion pumps. If the ion pumps are turned off by removing their energy source, or by adding an inhibitor such as
ouabain
Ouabain or (from Somali ''waabaayo'', "arrow poison" through French ''ouabaïo'') also known as g-strophanthin, is a plant derived toxic substance that was traditionally used as an arrow poison in eastern Africa for both hunting and warfare. ...
, the axon can still fire hundreds of thousands of action potentials before their amplitudes begin to decay significantly.
In particular, ion pumps play no significant role in the repolarization of the membrane after an action potential.
Another functionally important ion pump is the
sodium-calcium exchanger
The sodium-calcium exchanger (often denoted Na+/Ca2+ exchanger, exchange protein, or NCX) is an antiporter membrane protein that removes calcium from cells. It uses the energy that is stored in the electrochemical gradient of sodium (Na+) by al ...
. This pump operates in a conceptually similar way to the sodium-potassium pump, except that in each cycle it exchanges three Na
+ from the extracellular space for one Ca
++ from the intracellular space. Because the net flow of charge is inward, this pump runs "downhill", in effect, and therefore does not require any energy source except the membrane voltage. Its most important effect is to pump calcium outward—it also allows an inward flow of sodium, thereby counteracting the sodium-potassium pump, but, because overall sodium and potassium concentrations are much higher than calcium concentrations, this effect is relatively unimportant. The net result of the sodium-calcium exchanger is that in the resting state, intracellular calcium concentrations become very low.
Ion channels
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 are
integral membrane protein
An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a signi ...
s with a pore through which ions can travel between extracellular space and cell interior. Most channels are specific (selective) for one ion; for example, most potassium channels are characterized by 1000:1 selectivity ratio for potassium over sodium, though potassium and sodium ions have the same charge and differ only slightly in their radius. The channel pore is typically so small that ions must pass through it in single-file order.
* Channel pores can be either open or closed for ion passage, although a number of channels demonstrate various sub-conductance levels. When a channel is open, ions permeate through the channel pore down the transmembrane concentration gradient for that particular ion. Rate of ionic flow through the channel, i.e. single-channel current amplitude, is determined by the maximum channel conductance and electrochemical driving force for that ion, which is the difference between the instantaneous value of the membrane potential and the value of the
reversal potential In a biological membrane, the reversal potential is the membrane potential at which the direction of ionic current reverses. At the reversal potential, there is no net flow of ions from one side of the membrane to the other. For channels that are pe ...
.
[Junge, pp. 33–37.]
![Potassium channel1](https://upload.wikimedia.org/wikipedia/commons/5/5a/Potassium_channel1.png)
A channel may have several different states (corresponding to different
conformations of the protein), but each such state is either open or closed. In general, closed states correspond either to a contraction of the pore—making it impassable to the ion—or to a separate part of the protein, stoppering the pore. For example, the voltage-dependent sodium channel undergoes ''inactivation'', in which a portion of the protein swings into the pore, sealing it. This inactivation shuts off the sodium current and plays a critical role in the action potential.
Ion channels can be classified by how they respond to their environment.
For example, the ion channels involved in the action potential are ''voltage-sensitive channels''; they open and close in response to the voltage across the membrane. ''Ligand-gated channels'' form another important class; these ion channels open and close in response to the binding of a
ligand molecule, such as 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 ...
. Other ion channels open and close with mechanical forces. Still other ion channels—such as those of
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—open and close in response to other stimuli, such as light, temperature or pressure.
Leakage channels
Leakage channel
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 includin ...
s are the simplest type of ion channel, in that their permeability is more or less constant. The types of leakage channels that have the greatest significance in neurons are potassium and chloride channels. Even these are not perfectly constant in their properties: First, most of them are voltage-dependent in the sense that they conduct better in one direction than the other (in other words, they are
rectifier
A rectifier is an electrical device that converts alternating current (AC), which periodically reverses direction, to direct current (DC), which flows in only one direction. The reverse operation (converting DC to AC) is performed by an Power ...
s); second, some of them are capable of being shut off by chemical ligands even though they do not require ligands in order to operate.
Ligand-gated channels
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 are channels whose permeability is greatly increased when some type of chemical ligand binds to the protein structure. Animal cells contain hundreds, if not thousands, of types of these. A large subset function as
neurotransmitter receptor
A neurotransmitter receptor (also known as a neuroreceptor) is a membrane receptor protein that is activated by a neurotransmitter. Chemicals on the outside of the cell, such as a neurotransmitter, can bump into the cell's membrane, in which the ...
s—they occur at
postsynaptic
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 sys ...
sites, and the chemical ligand that gates them is released by the presynaptic
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 ...
. One example of this type is the
AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synapse, synap ...
, a receptor for the neurotransmitter
glutamate
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
that when activated allows passage of sodium and potassium ions. Another example is the
GABAA receptor, a receptor for the neurotransmitter
GABA that when activated allows passage of chloride ions.
Neurotransmitter receptors are activated by ligands that appear in the extracellular area, but there are other types of ligand-gated channels that are controlled by interactions on the intracellular side.
Voltage-dependent channels
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, also known as ''voltage dependent ion channels'', are channels whose permeability is influenced by the membrane potential. They form another very large group, with each member having a particular ion selectivity and a particular voltage dependence. Many are also time-dependent—in other words, they do not respond immediately to a voltage change but only after a delay.
One of the most important members of this group is a type of voltage-gated sodium channel that underlies action potentials—these are sometimes called ''Hodgkin-Huxley sodium channels'' because they were initially characterized 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 b ...
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 on ...
in their Nobel Prize-winning studies of the physiology of the action potential. The channel is closed at the resting voltage level, but opens abruptly when the voltage exceeds a certain threshold, allowing a large influx of sodium ions that produces a very rapid change in the membrane potential. Recovery from an action potential is partly dependent on a type of voltage-gated potassium channel that is closed at the resting voltage level but opens as a consequence of the large voltage change produced during the action potential.
Reversal potential
The
reversal potential In a biological membrane, the reversal potential is the membrane potential at which the direction of ionic current reverses. At the reversal potential, there is no net flow of ions from one side of the membrane to the other. For channels that are pe ...
(or ''equilibrium potential'') of an ion is the value of transmembrane voltage at which diffusive and electrical forces counterbalance, so that there is no net ion flow across the membrane. This means that the transmembrane voltage exactly opposes the force of diffusion of the ion, such that the net current of the ion across the membrane is zero and unchanging. The reversal potential is important because it gives the voltage that acts on channels permeable to that ion—in other words, it gives the voltage that the ion concentration gradient generates when it acts as a
battery
Battery most often refers to:
* Electric battery, a device that provides electrical power
* Battery (crime), a crime involving unlawful physical contact
Battery may also refer to:
Energy source
*Automotive battery, a device to provide power t ...
.
The equilibrium potential of a particular ion is usually designated by the notation ''E''
ion.The equilibrium potential for any ion can be calculated using the
Nernst equation
In electrochemistry, the Nernst equation is a Thermodynamics#Chemical thermodynamics, chemical thermodynamical relationship that permits the calculation of the reduction potential of a reaction (half-cell or electrochemical cell, full cell reacti ...
.
[Purves ''et al.'', pp. 28–32; ]Bullock
Bullock may refer to:
Animals
* Bullock (in British English), a castrated male bovine animal of any age
* Bullock (in North America), a young bull (an uncastrated male bovine animal)
* Bullock (in Australia, India and New Zealand), an ox, an adu ...
, Orkand, and Grinnell, pp. 133–134; Schmidt-Nielsen, pp. 478–480, 596–597; Junge, pp. 33–35 For example, reversal potential for potassium ions will be as follows:
:
where
* ''E''
eq,K+ is the equilibrium potential for potassium, measured in
volt
The volt (symbol: V) is the unit of electric potential, electric potential difference (voltage), and electromotive force in the International System of Units (SI). It is named after the Italian physicist Alessandro Volta (1745–1827).
Defi ...
s
* ''R'' is the universal
gas constant
The molar gas constant (also known as the gas constant, universal gas constant, or ideal gas constant) is denoted by the symbol or . It is the molar equivalent to the Boltzmann constant, expressed in units of energy per temperature increment per ...
, equal to 8.314
joule
The joule ( , ; symbol: J) is the unit of energy in the International System of Units (SI). It is equal to the amount of work done when a force of 1 newton displaces a mass through a distance of 1 metre in the direction of the force applied ...
s·K
−1·mol
−1
* ''T'' is the
absolute temperature
Thermodynamic temperature is a quantity defined in thermodynamics as distinct from kinetic theory or statistical mechanics.
Historically, thermodynamic temperature was defined by Kelvin in terms of a macroscopic relation between thermodynamic wor ...
, measured in
kelvin
The kelvin, symbol K, is the primary unit of temperature in the International System of Units (SI), used alongside its prefixed forms and the degree Celsius. It is named after the Belfast-born and University of Glasgow-based engineer and phys ...
s (= K = degrees Celsius + 273.15)
* ''z'' is the number of
elementary charge
The elementary charge, usually denoted by is the electric charge carried by a single proton or, equivalently, the magnitude of the negative electric charge carried by a single electron, which has charge −1 . This elementary charge is a fundame ...
s of the ion in question involved in the reaction
* ''F'' is the
Faraday constant
In physical chemistry, the Faraday constant, denoted by the symbol and sometimes stylized as ℱ, is the electric charge per mole of elementary charges. It is named after the English scientist Michael Faraday. Since the 2019 redefinition of S ...
, equal to 96,485
coulomb
The coulomb (symbol: C) is the unit of electric charge in the International System of Units (SI).
In the present version of the SI it is equal to the electric charge delivered by a 1 ampere constant current in 1 second and to elementary char ...
s·mol
−1 or J·V
−1·mol
−1
*
+">+sub>o is the extracellular concentration of potassium, measured in
mol·m
−3 or mmol·l
−1
*
+">+sub>i is the intracellular concentration of potassium
Even if two different ions have the same charge (i.e., K
+ and Na
+), they can still have very different equilibrium potentials, provided their outside and/or inside concentrations differ. Take, for example, the equilibrium potentials of potassium and sodium in neurons. The potassium equilibrium potential ''E''
K is −84 mV with 5 mM potassium outside and 140 mM inside. On the other hand, the sodium equilibrium potential, ''E''
Na, is approximately +66 mV with approximately 12 mM sodium inside and 140 mM outside.
[Note that the signs of ''E''Na and ''E''K are opposite. This is because the concentration gradient for potassium is directed out of the cell, while the concentration gradient for sodium is directed into the cell. Membrane potentials are defined relative to the exterior of the cell; thus, a potential of −70 mV implies that the interior of the cell is negative relative to the exterior.]
Changes to membrane potential during development
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 resting membrane potential actually changes during the
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
*Photographi ...
of an organism. In order for a neuron to eventually adopt its full adult function, its potential must be tightly regulated during development. As an organism progresses through development the resting membrane potential becomes more negative.
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 mye ...
are also differentiating and proliferating as development progresses in the
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
. The addition of these glial cells increases the organism's ability to regulate extracellular
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 ...
. The drop in extracellular potassium can lead to a decrease in membrane potential of 35 mV.
Cell excitability
Cell excitability is the change in membrane potential that is necessary for cellular responses in various tissues. Cell excitability is a property that is induced during early embriogenesis. Excitability of a cell has also been defined as the ease with which a response may be triggered. The resting and
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 ...
s forms the basis of cell excitability and these processes are fundamental for the generation of graded and action potentials.
The most important
regulators
Regulator may refer to:
Technology
* Regulator (automatic control), a device that maintains a designated characteristic, as in:
** Battery regulator
** Pressure regulator
** Diving regulator
** Voltage regulator
* Regulator (sewer), a control de ...
of cell excitability are the extracellular
electrolyte
An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon dis ...
concentrations (i.e. Na
+, K
+,
Ca2+, Cl
−,
Mg2+) and associated proteins. Important proteins that regulate cell excitability are
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,
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 produc ...
s (e.g.
Na+/K+-ATPase
NA, N.A., Na, nA or n/a may refer to:
Chemistry and physics
* Sodium, symbol Na, a chemical element
* Avogadro constant (''N''A)
* Nucleophilic addition, a type of reaction in organic chemistry
* Numerical aperture, a number that characterizes ...
,
magnesium transporter Magnesium transporters are proteins that transport magnesium across the cell membrane. All forms of life require magnesium, yet the molecular mechanisms of Mg2+ uptake from the environment and the distribution of this vital element within the organi ...
s,
acid–base transporters),
membrane receptors
A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
and
hyperpolarization-activated cyclic-nucleotide-gated channels. For example,
potassium channels
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 ...
and
calcium-sensing receptor
The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ions. It is primarily expressed in the parathyroid gland, the renal tubules of the kidney and the brain. In the parathyroid ...
s are important regulators of excitability in
neurons
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 ...
,
cardiac myocytes
Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate Muscle tissue, muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striat ...
and many other excitable cells like
astrocytes
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endo ...
. Calcium ion is also the most important
second messenger
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first me ...
in excitable
cell signaling
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 ...
. Activation of synaptic receptors initiates
long-lasting changes in neuronal excitability.
Thyroid
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
,
adrenal
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...
and other hormones also regulate cell excitability, for example,
progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
and
estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
modulate
myometrial smooth muscle cell
The myometrium is the middle layer of the uterine wall, consisting mainly of uterine smooth muscle cells (also called uterine myocytes) but also of supporting stromal and vascular tissue. Its main function is to induce uterine contractions.
Struc ...
excitability.
Many cell types are considered to have an excitable membrane. Excitable cells are neurons, myocytes (cardiac, skeletal,
smooth
Smooth may refer to:
Mathematics
* Smooth function, a function that is infinitely differentiable; used in calculus and topology
* Smooth manifold, a differentiable manifold for which all the transition maps are smooth functions
* Smooth algebraic ...
), vascular
endothelial cells
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
,
pericyte
Pericytes (previously known as Rouget cells) are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries throughout the body. Pericytes are embedded in the basement membrane of blood ca ...
s,
juxtaglomerular cell
Juxtaglomerular cells (JG cells), also known as juxtaglomerular granular cells are cells in the kidney that synthesize, store, and secrete the enzyme renin. They are specialized smooth muscle cells mainly in the walls of the afferent arteriol ...
s,
interstitial cells of Cajal
Interstitial cells of Cajal (ICC) are interstitial cells found in the gastrointestinal tract. There are different types of ICC with different functions. ICC and another type of interstitial cell, known as platelet-derived growth factor receptor ...
, many types of
epithelial cells
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
(e.g.
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,
alpha cell
Alpha cells (α cells) are endocrine cells that are found in the Islets of langerhans, Islets of Langerhans in the pancreas. Alpha cells secrete the peptide hormone glucagon in order to increase glucose levels in the blood stream.
Discovery
Isle ...
s,
delta cell
Delta cells (δ-cells or D cells) are somatostatin-producing cells. They can be found in the stomach, intestine and the pancreatic islets. Delta cells comprise ca 5% of the cells in the islets but may interact with many more islet cells than sugg ...
s,
enteroendocrine cell
Enteroendocrine cells are specialized cells of the gastrointestinal tract and pancreas with endocrine function. They produce gastrointestinal hormones or peptides in response to various stimuli and release them into the bloodstream for systemic ef ...
s,
pulmonary neuroendocrine cells,
pinealocyte
Pinealocytes are the main cells contained in the pineal gland, located behind the third ventricle and between the two hemispheres of the brain. The primary function of the pinealocytes is the secretion of the hormone melatonin, important in the r ...
s),
glia
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 mye ...
l cells (e.g. astrocytes),
mechanoreceptor
A mechanoreceptor, also called mechanoceptor, is a sensory receptor that responds to mechanical pressure or distortion. Mechanoreceptors are innervated by sensory neurons that convert mechanical pressure into electrical signals that, in animals, ...
cells (e.g.
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 and
Merkel cell
Merkel cells, also known as Merkel-Ranvier cells or tactile epithelial cells, are oval-shaped mechanoreceptors essential for light touch sensation and found in the skin of vertebrates. They are abundant in highly sensitive skin like that of the f ...
s),
chemoreceptor
A chemoreceptor, also known as chemosensor, is a specialized sensory receptor which transduces a chemical substance (endogenous or induced) to generate a biological signal. This signal may be in the form of an action potential, if the chemorecept ...
cells (e.g.
glomus cell
Glomus cells are the cell type mainly located in the carotid bodies and aortic bodies. Glomus type I cells are peripheral chemoreceptors which sense the oxygen, carbon dioxide and pH levels of the blood. When there is a decrease in the blood's pH ...
s,
taste receptor
A taste receptor or tastant is a type of cellular receptor which facilitates the sensation of taste. When food or other substances enter the mouth, molecules interact with saliva and are bound to taste receptors in the oral cavity and other locat ...
s), some
plant cells
Plant cells are the cells present in green plants, photosynthetic eukaryotes of the kingdom Plantae. Their distinctive features include primary cell walls containing cellulose, hemicelluloses and pectin, the presence of plastids with the capabi ...
and possibly
immune cells
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
. Astrocytes display a form of non-electrical excitability based on intracellular calcium variations related to the expression of several receptors through which they can detect the synaptic signal. In neurons, there are different membrane properties in some portions of the cell, for example, dendritic excitability endows neurons with the capacity for coincidence detection of spatially separated inputs.
Equivalent circuit
![Cell membrane equivalent circuit](https://upload.wikimedia.org/wikipedia/commons/e/e5/Cell_membrane_equivalent_circuit.svg)
Electrophysiologists model the effects of ionic concentration differences, ion channels, and membrane capacitance in terms of an
equivalent circuit In electrical engineering and science, an equivalent circuit refers to a theoretical circuit that retains all of the electrical characteristics of a given circuit. Often, an equivalent circuit is sought that simplifies calculation, and more broadly ...
, which is intended to represent the electrical properties of a small patch of membrane. The equivalent circuit consists of a capacitor in parallel with four pathways each consisting of a battery in series with a variable conductance. The capacitance is determined by the properties of the lipid bilayer, and is taken to be fixed. Each of the four parallel pathways comes from one of the principal ions, sodium, potassium, chloride, and calcium. The voltage of each ionic pathway is determined by the concentrations of the ion on each side of the membrane; see the
Reversal potential In a biological membrane, the reversal potential is the membrane potential at which the direction of ionic current reverses. At the reversal potential, there is no net flow of ions from one side of the membrane to the other. For channels that are pe ...
section above. The conductance of each ionic pathway at any point in time is determined by the states of all the ion channels that are potentially permeable to that ion, including leakage channels, ligand-gated channels, and voltage-gated ion channels.
![Cell membrane reduced circuit](https://upload.wikimedia.org/wikipedia/commons/b/b6/Cell_membrane_reduced_circuit.svg)
For fixed ion concentrations and fixed values of ion channel conductance, the equivalent circuit can be further reduced, using 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 th ...
as described below, to a circuit containing a capacitance in parallel with a battery and conductance. In electrical terms, this is a type of
RC circuit
A resistor–capacitor circuit (RC circuit), or RC filter or RC network, is an electric circuit composed of resistors and capacitors. It may be driven by a voltage or current source and these will produce different responses. A first order RC ci ...
(resistance-capacitance circuit), and its electrical properties are very simple. Starting from any initial state, the current flowing across either the conductance or the capacitance decays with an exponential time course, with a time constant of , where is the capacitance of the membrane patch, and is the net resistance. For realistic situations, the time constant usually lies in the 1—100 millisecond range. In most cases, changes in the conductance of ion channels occur on a faster time scale, so an RC circuit is not a good approximation; however, the differential equation used to model a membrane patch is commonly a modified version of the RC circuit equation.
Resting potential
When the membrane potential of a cell goes for a long period of time without changing significantly, it is referred to as a
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 oppo ...
or resting voltage. This term is used for the membrane potential of non-excitable cells, but also for the membrane potential of excitable cells in the absence of excitation. In excitable cells, the other possible states are graded membrane potentials (of variable amplitude), and action potentials, which are large, all-or-nothing rises in membrane potential that usually follow a fixed time course. Excitable cells 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, and some secretory cells in
gland
In animals, a gland is a group of cells in an animal's body that synthesizes substances (such as hormones) for release into the bloodstream (endocrine gland) or into cavities inside the body or its outer surface (exocrine gland).
Structure
De ...
s. Even in other types of cells, however, the membrane voltage can undergo changes in response to environmental or intracellular stimuli. For example, depolarization of the plasma membrane appears to be an important step in
programmed cell death
Programmed cell death (PCD; sometimes referred to as cellular suicide) is the death of a cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers advantage durin ...
.
The interactions that generate the resting potential are modeled by 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 th ...
.
[Purves ''et al.'', pp. 32–33; ]Bullock
Bullock may refer to:
Animals
* Bullock (in British English), a castrated male bovine animal of any age
* Bullock (in North America), a young bull (an uncastrated male bovine animal)
* Bullock (in Australia, India and New Zealand), an ox, an adu ...
, Orkand, and Grinnell, pp. 138–140; Schmidt-Nielsen, pp. 480; Junge, pp. 35–37 This is similar in form to the Nernst equation shown above, in that it is based on the charges of the ions in question, as well as the difference between their inside and outside concentrations. However, it also takes into consideration the relative permeability of the plasma membrane to each ion in question.
:
The three ions that appear in this equation are potassium (K
+), sodium (Na
+), and chloride (Cl
−). Calcium is omitted, but can be added to deal with situations in which it plays a significant role.
Being an anion, the chloride terms are treated differently from the cation terms; the intracellular concentration is in the numerator, and the extracellular concentration in the denominator, which is reversed from the cation terms. ''P''
i stands for the relative permeability of the ion type i.
In essence, the Goldman formula expresses the membrane potential as a weighted average of the reversal potentials for the individual ion types, weighted by permeability. (Although the membrane potential changes about 100 mV during an action potential, the concentrations of ions inside and outside the cell do not change significantly. They remain close to their respective concentrations when then membrane is at resting potential.) In most animal cells, the permeability to potassium is much higher in the resting state than the permeability to sodium. As a consequence, the resting potential is usually close to the potassium reversal potential.
[Purves ''et al.'', p. 34; ]Bullock
Bullock may refer to:
Animals
* Bullock (in British English), a castrated male bovine animal of any age
* Bullock (in North America), a young bull (an uncastrated male bovine animal)
* Bullock (in Australia, India and New Zealand), an ox, an adu ...
, Orkand, and Grinnell, p. 134; Schmidt-Nielsen, pp. 478–480.[Purves ''et al.'', pp. 33–36; ]Bullock
Bullock may refer to:
Animals
* Bullock (in British English), a castrated male bovine animal of any age
* Bullock (in North America), a young bull (an uncastrated male bovine animal)
* Bullock (in Australia, India and New Zealand), an ox, an adu ...
, Orkand, and Grinnell, p. 131. The permeability to chloride can be high enough to be significant, but, unlike the other ions, chloride is not actively pumped, and therefore equilibrates at a reversal potential very close to the resting potential determined by the other ions.
Values of resting membrane potential in most animal cells usually vary between the potassium reversal potential (usually around -80 mV) and around -40 mV. The resting potential in excitable cells (capable of producing action potentials) is usually near -60 mV—more depolarized voltages would lead to spontaneous generation of action potentials. Immature or undifferentiated cells show highly variable values of resting voltage, usually significantly more positive than in differentiated cells.
In such cells, the resting potential value correlates with the degree of differentiation: undifferentiated cells in some cases may not show any transmembrane voltage difference at all.
Maintenance of the resting potential can be metabolically costly for a cell because of its requirement for active pumping of ions to counteract losses due to leakage channels. The cost is highest when the cell function requires an especially depolarized value of membrane voltage. For example, the resting potential in daylight-adapted
blowfly (''Calliphora vicina'')
photoreceptors can be as high as -30 mV.
This elevated membrane potential allows the cells to respond very rapidly to visual inputs; the cost is that maintenance of the resting potential may consume more than 20% of overall cellular
ATP
ATP may refer to:
Companies and organizations
* Association of Tennis Professionals, men's professional tennis governing body
* American Technical Publishers, employee-owned publishing company
* ', a Danish pension
* Armenia Tree Project, non ...
.
On the other hand, the high resting potential in undifferentiated cells does not necessarily incur a high metabolic cost. This apparent paradox is resolved by examination of the origin of that resting potential. Little-differentiated cells are characterized by extremely high input resistance,
which implies that few leakage channels are present at this stage of cell life. As an apparent result, potassium permeability becomes similar to that for sodium ions, which places resting potential in-between the reversal potentials for sodium and potassium as discussed above. The reduced leakage currents also mean there is little need for active pumping in order to compensate, therefore low metabolic cost.
Graded potentials
As explained above, the potential at any point in a cell's membrane is determined by the ion concentration differences between the intracellular and extracellular areas, and by the permeability of the membrane to each type of ion. The ion concentrations do not normally change very quickly (with the exception of Ca
2+, where the baseline intracellular concentration is so low that even a small influx may increase it by orders of magnitude), but the permeabilities of the ions can change in a fraction of a millisecond, as a result of activation of ligand-gated ion channels. The change in membrane potential can be either large or small, depending on how many ion channels are activated and what type they are, and can be either long or short, depending on the lengths of time that the channels remain open. Changes of this type are referred to as graded potentials, in contrast to action potentials, which have a fixed amplitude and time course.
As can be derived from 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 th ...
shown above, the effect of increasing the permeability of a membrane to a particular type of ion shifts the membrane potential toward the reversal potential for that ion. Thus, opening Na
+ channels shifts the membrane potential toward the Na
+ reversal potential, which is usually around +100 mV. Likewise, opening K
+ channels shifts the membrane potential toward about –90 mV, and opening Cl
− channels shifts it toward about –70 mV (resting potential of most membranes). Thus, Na
+ channels shift the membrane potential in a positive direction, K
+ channels shift it in a negative direction (except when the membrane is hyperpolarized to a value more negative than the K
+ reversal potential), and Cl
− channels tend to shift it towards the resting potential.
![IPSPsummation](https://upload.wikimedia.org/wikipedia/commons/a/a1/IPSPsummation.JPG)
Graded membrane potentials are particularly important in
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, where they are produced by
synapse
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 ...
s—a temporary change in membrane potential produced by activation of a synapse by a single graded or action potential is called a
postsynaptic potential
Postsynaptic potentials are changes in the membrane potential of the postsynaptic terminal of a chemical synapse. Postsynaptic potentials are graded potentials, and should not be confused with action potentials although their function is to ini ...
.
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 that act to open Na
+ channels typically cause the membrane potential to become more positive, while neurotransmitters that activate K
+ channels typically cause it to become more negative; those that inhibit these channels tend to have the opposite effect.
Whether a postsynaptic potential is considered excitatory or inhibitory depends on the reversal potential for the ions of that current, and the threshold for the cell to fire an action potential (around –50mV). A postsynaptic current with a reversal potential above threshold, such as a typical Na
+ current, is considered excitatory. A current with a reversal potential below threshold, such as a typical K
+ current, is considered inhibitory. A current with a reversal potential above the resting potential, but below threshold, will not by itself elicit action potentials, but will produce
subthreshold membrane potential oscillations
Subthreshold membrane potential oscillations are membrane oscillations that do not directly trigger an action potential since they do not reach the necessary threshold for firing. However, they may facilitate sensory signal processing.
Neurons pro ...
. Thus, neurotransmitters that act to open Na
+ channels produce
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, or EPSPs, whereas neurotransmitters that act to open K
+ or Cl
− channels typically produce
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, or IPSPs. When multiple types of channels are open within the same time period, their postsynaptic potentials summate (are added together).
Other values
From the viewpoint of biophysics, the ''resting'' membrane potential is merely the membrane potential that results from the membrane permeabilities that predominate when the cell is resting. The above equation of weighted averages always applies, but the following approach may be more easily visualized.
At any given moment, there are two factors for an ion that determine how much influence that ion will have over the membrane potential of a cell:
# That ion's driving force
# That ion's permeability
If the driving force is high, then the ion is being "pushed" across the membrane. If the permeability is high, it will be easier for the ion to diffuse across the membrane.
* Driving force is the net electrical force available to move that ion across the membrane. It is calculated as the difference between the voltage that the ion "wants" to be at (its equilibrium potential) and the actual membrane potential (''E''
m). So, in formal terms, the driving force for an ion = ''E''
m - ''E''
ion
* For example, at our earlier calculated resting potential of −73 mV, the driving force on potassium is 7 mV : (−73 mV) − (−80 mV) = 7 mV. The driving force on sodium would be (−73 mV) − (60 mV) = −133 mV.
* Permeability is a measure of how easily an ion can cross the membrane. It is normally measured as the (electrical) conductance and the unit,
siemens
Siemens AG ( ) is a German multinational conglomerate corporation and the largest industrial manufacturing company in Europe headquartered in Munich with branch offices abroad.
The principal divisions of the corporation are ''Industry'', '' ...
, corresponds to 1 C·s
−1·V
−1, that is one
coulomb
The coulomb (symbol: C) is the unit of electric charge in the International System of Units (SI).
In the present version of the SI it is equal to the electric charge delivered by a 1 ampere constant current in 1 second and to elementary char ...
per second per volt of potential.
So, in a resting membrane, while the driving force for potassium is low, its permeability is very high. Sodium has a huge driving force but almost no resting permeability. In this case, potassium carries about 20 times more current than sodium, and thus has 20 times more influence over ''E''
m than does sodium.
However, consider another case—the peak of the action potential. Here, permeability to Na is high and K permeability is relatively low. Thus, the membrane moves to near ''E''
Na and far from ''E''
K.
The more ions are permeant the more complicated it becomes to predict the membrane potential. However, this can be done using the
Goldman-Hodgkin-Katz equation or the weighted means equation. By plugging in the concentration gradients and the permeabilities of the ions at any instant in time, one can determine the membrane potential at that moment. What the GHK equations means is that, at any time, the value of the membrane potential will be a weighted average of the equilibrium potentials of all permeant ions. The "weighting" is the ions relative permeability across the membrane.
Effects and implications
While cells expend energy to transport ions and establish a transmembrane potential, they use this potential in turn to transport other ions and metabolites such as sugar. The transmembrane potential of the
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
drives the production of
ATP
ATP may refer to:
Companies and organizations
* Association of Tennis Professionals, men's professional tennis governing body
* American Technical Publishers, employee-owned publishing company
* ', a Danish pension
* Armenia Tree Project, non ...
, which is the common currency of biological energy.
Cells may draw on the energy they store in the resting potential to drive action potentials or other forms of excitation. These changes in the membrane potential enable communication with other cells (as with action potentials) or initiate changes inside the cell, which happens in an
egg
An egg is an organic vessel grown by an animal to carry a possibly fertilized egg cell (a zygote) and to incubate from it an embryo within the egg until the embryo has become an animal fetus that can survive on its own, at which point the a ...
when it is
fertilized
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
by a
sperm
Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...
.
In neuronal cells, an action potential begins with a rush of sodium ions into the cell through sodium channels, resulting in depolarization, while recovery involves an outward rush of potassium through potassium channels. Both of these fluxes occur by
passive diffusion
Passive transport is a type of membrane transport that does not require energy to move substances across cell membranes. Instead of using cellular energy, like active transport, passive transport relies on the second law of thermodynamics to d ...
.
Changes in the dielectric properties of plasma membrane may act as hallmark of underlying conditions such as diabetes and dyslipidemia.
See also
*
Bioelectrochemistry
Bioelectrochemistry is a branch of electrochemistry and biophysical chemistry concerned with electrophysiological topics like cell electron-proton transport, cell membrane potentials and electrode reactions of redox enzymes.
History
The beginnin ...
*
Chemiosmotic potential
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and th ...
*
Electrochemical potential
In electrochemistry, the electrochemical potential (ECP), ', is a thermodynamic measure of chemical potential that does not omit the energy contribution of electrostatics. Electrochemical potential is expressed in the unit of J/ mol.
Introductio ...
*
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 th ...
*
Membrane biophysics Membrane biology is the study of the biological and physiochemical characteristics of membranes, with applications in the study of cellular physiology.
Membrane bioelectrical impulses are described by the Hodgkin cycle.
Biophysics
Membrane bioph ...
*
Microelectrode array
Microelectrode arrays (MEAs) (also referred to as multielectrode arrays) are devices that contain multiple (tens to thousands) microelectrodes through which neural signals are obtained or delivered, essentially serving as neural interfaces that co ...
*
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 ...
*
Surface potential
Surface charge is a two-dimensional surface with non-zero electric charge. These electric charges are constrained on this 2-D surface, and surface charge density, measured in coulombs per square meter (C•m−2), is used to describe the charge di ...
*
Gibbs–Donnan effect
The Gibbs–Donnan effect (also known as the Donnan's effect, Donnan law, Donnan equilibrium, or Gibbs–Donnan equilibrium) is a name for the behaviour of charged particles near a semi-permeable membrane that sometimes fail to distribute evenly ...
*
Synaptic potential
Synaptic potential refers to the potential difference across the postsynaptic membrane that results from the action of neurotransmitters at a neuronal synapse. In other words, it is the “incoming” signal that a neuron receives. There are two fo ...
Notes
References
Further reading
* Alberts et al. ''Molecular Biology of the Cell''. Garland Publishing; 4th Bk&Cdr edition (March, 2002). . Undergraduate level.
* Guyton, Arthur C., John E. Hall. ''Textbook of medical physiology''. W.B. Saunders Company; 10th edition (August 15, 2000). . Undergraduate level.
* Hille, B. ''Ionic Channel of Excitable Membranes'' Sinauer Associates, Sunderland, MA, USA; 1st Edition, 1984.
* Nicholls, J.G., Martin, A.R. and Wallace, B.G. ''From Neuron to Brain'' Sinauer Associates, Inc. Sunderland, MA, USA 3rd Edition, 1992.
* Ove-Sten Knudsen. ''Biological Membranes: Theory of Transport, Potentials and Electric Impulses''. Cambridge University Press (September 26, 2002). . Graduate level.
* National Medical Series for Independent Study. ''Physiology''. Lippincott Williams & Wilkins. Philadelphia, PA, USA 4th Edition, 2001.
External links
Functions of the Cell MembraneNernst/Goldman Equation Simulator- Online interactive tutorial (Flash)
{{DEFAULTSORT:Membrane Potential
Cell communication
Cell signaling
Cellular processes
Cellular neuroscience
Electrochemical concepts
Electrophysiology
Membrane biology