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Ion channels are pore-forming
membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...

membrane protein
s that allow
ions An ion () is an atom An atom is the smallest unit of ordinary matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are u ...

ions
to pass through the channel pore. Their functions include establishing a
resting membrane potentialA 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 ...
, shaping
action potential In physiology, an action potential (AP) occurs when the membrane potential of a specific Cell (biology), cell location rapidly rises and falls: this depolarization then causes adjacent locations to similarly depolarize. Action potentials occur ...

action potential
s and other electrical signals by gating the flow of
ion An ion () is an atom An atom is the smallest unit of ordinary matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are ...
s across the
cell membrane cell membrane vs. Prokaryotes A prokaryote is a typically unicellular organism that lacks a nuclear membrane-enclosed cell nucleus, nucleus. The word ''prokaryote'' comes from the Greek language, Greek (, 'before') and (, 'nut' or 'kernel').C ...

cell membrane
, controlling the flow of ions across secretory and
epithelial cell Epithelium is one of the four basic types of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume o ...
s, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of
ionophoric
ionophoric
proteins, the other being
ion transporterIn 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 producti ...
s. The study of ion channels often involves
biophysics uses protein domain dynamics on nanoscale Image:Protein translation.gif, 300px, A ribosome is a biological machine that utilizes nanoscale protein dynamics The nanoscopic scale (or nanoscale) usually refers to structures with a length scale ...
,
electrophysiology Electrophysiology (from Greek , ''ēlektron'', "amber" etymology of "electron"">Electron#Etymology">etymology of "electron" , ''physis'', "nature, origin"; and , '' -logia'') is the branch of physiology Physiology (; ) is the scientific study ...
, and
pharmacology Pharmacology is a branch of , and concerned with or action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemical or physiological effect on the cell, tissue, organ ...
, while using techniques including
voltage clamp The voltage clamp is an experimental method used by electrophysiologists to measure the ion currents Currents or The Current may refer to: Science and technology * Current (fluid), the flow of a liquid or a gas ** Air current, a flow of air * ...

voltage clamp
,
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 ...

patch clamp
,
immunohistochemistry targeting the protein Neprilysin, CD10. Image:HSP IF IgA.jpg, 200px, Immunofluorescence of human skin using an anti-IgA antibody. The skin is from a patient with Henoch–Schönlein purpura: IgA deposits are found in the walls of small superficial ...

immunohistochemistry
,
X-ray crystallography X-ray crystallography (XRC) is the experimental science determining the atomic and molecular structure of a crystal A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a ...

X-ray crystallography
,
fluoroscopy Image:Normal barium swallow animation.gif, A barium swallow exam taken via fluoroscopy. Fluoroscopy () is an imaging technique that uses X-rays to obtain real-time moving images of the interior of an object. In its primary application of medical i ...

fluoroscopy
, and
RT-PCR Reverse transcription polymerase chain reaction (RT-PCR) is a laboratory technique combining reverse transcription of RNA into DNA (in this context called complementary DNA or cDNA) and amplification of specific DNA targets using polymerase chai ...
. Their classification as molecules is referred to as
channelomicsThe channelome, sometimes called the "ion channelome", is the complete set of ion channel s (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane. ...
.


Basic features

There are two distinctive features of ion channels that differentiate them from other types of ion transporter proteins: #The rate of ion transport through the channel is very high (often 106 ions per second or greater). #Ions pass through channels down their
electrochemical gradient An electrochemical gradient is a of , usually for an that can move across a . The gradient consists of two parts, the chemical gradient, or difference in across a membrane, and the electrical gradient, or difference in across a membrane. When ...
, which is a function of ion concentration and membrane potential, "downhill", without the input (or help) of metabolic energy (e.g.
ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals * American Technical Publishers * ', a Danish pension * Armenia Tree Project * Association for Transpersonal Psychology * ATP architects engineers office * ATP ...

ATP
,
co-transport In cellular biology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, Physiology, function and behavior of cell (biology), cells. All living organisms are made of cells. A cell is the basic uni ...
mechanisms, or
active transport In cellular biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processe ...

active transport
mechanisms). Ion channels are located within the
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. Biological membranes include cell membranes (outer coverings of cells or organelles that all ...

membrane
of all excitable cells, and of many intracellular
organelle In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, M ...
s. They are often described as narrow, water-filled tunnels that allow only ions of a certain size and/or charge to pass through. This characteristic is called
selective permeability Selective may refer to: * Selective school A selective school is a school that admits students on the basis of some sort of selection criteria, usually academic. The term may have different connotations in different systems and is the opposite of a ...
. The archetypal channel pore is just one or two atoms wide at its narrowest point and is selective for specific species of ion, such as
sodium Sodium is a with the  Na (from Latin ''natrium'') and  11. It is a soft, silvery-white, highly reactive . Sodium is an , being in of the periodic table. Its only stable is 23Na. The free metal does not occur in nature, and must be ...

sodium
or
potassium Potassium is a chemical element upright=1.0, 500px, The chemical elements ordered by link=Periodic table In chemistry Chemistry is the science, scientific study of the properties and behavior of matter. It is a natural science ...

potassium
. However, some channels may be permeable to the passage of more than one type of ion, typically sharing a common charge: positive (
cation An ion () is an atom An atom is the smallest unit of ordinary matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are u ...
s) or negative (
anion An ion () is an atom An atom is the smallest unit of ordinary matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are u ...
s). Ions often move through the segments of the channel pore in single file nearly as quickly as the ions move through free solution. In many ion channels, passage through the pore is governed by a "gate", which may be opened or closed in response to chemical or electrical signals, temperature, or mechanical force. Ion channels are
integral membrane protein An integral membrane protein (IMP) is a type of membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Int ...
s, typically formed as assemblies of several individual proteins. Such "multi- subunit" assemblies usually involve a circular arrangement of identical or homologous proteins closely packed around a water-filled pore through the plane of the membrane or
lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane A polarized membrane is a lipid bilayer, lipid membrane that has a positive electrical charge on one side and a negative charge on another side, which produces the resting pote ...
. For most
voltage-gated ion channel Voltage-gated ion channels are a class of transmembrane proteins that form ion channel s (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane ...
s, the pore-forming subunit(s) are called the α subunit, while the auxiliary subunits are denoted β, γ, and so on.


Biological role

Because channels underlie the
nerve impulse In physiology, an action potential (AP) 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 type ...

nerve impulse
and because "transmitter-activated" channels mediate conduction across the
synapse In the nervous system In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiol ...

synapse
s, channels are especially prominent components of the
nervous system In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechani ...

nervous system
. Indeed, numerous toxins that organisms have evolved for shutting down the nervous systems of predators and prey (e.g., the venoms produced by spiders, scorpions, snakes, fish, bees, sea snails, and others) work by modulating ion channel conductance and/or kinetics. In addition, ion channels are key components in a wide variety of biological processes that involve rapid changes in cells, such as
cardiac The heart is a muscle, muscular Organ (anatomy), organ in most animals, which 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 ...

cardiac
,
skeletal The skeleton refers to the frames of support of animal bodies. There are several different skeletal types: the exoskeleton An exoskeleton (from Greek έξω, ''éxō'' "outer" and σκελετός, ''skeletós'' "skeleton") is the external sk ...

skeletal
, and
smooth muscle Smooth muscle is an involuntary non-striated muscle Striated muscle tissue is a muscle tissue Muscle tissue is a soft tissue that composes muscles in animal bodies, and gives rise to muscles' ability to contract. It is also referred to as myo ...

smooth muscle
,
epithelial Epithelium is one of the four basic types of animal Tissue (biology), tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed Cell (biology), cells with little Extr ...
transport of nutrients and ions,
T-cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system, and play a central role in the adaptive immune response. T cells can be easily distinguished from other lymphocytes by the presence of a T- ...
activation and
pancreatic The pancreas is an organ of the digestive system The human digestive system consists of the human gastrointestinal tract, gastrointestinal tract plus the accessory organs of digestion (the tongue, salivary glands, pancreas, liver, and gallb ...

pancreatic
beta-cell
insulin Insulin (, from Latin Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally spoken in the area around Rome, known as Latium. Through the power of the Roman Republi ...

insulin
release. In the search for new drugs, ion channels are a frequent target.


Diversity

There are over 300 types of ion channels just in the cells of the inner ear. Ion channels may be classified by the nature of their gating, the species of ions passing through those gates, the number of gates (pores) and localization of proteins. Further heterogeneity of ion channels arises when channels with different constitutive subunits give rise to a specific kind of current. Absence or mutation of one or more of the contributing types of channel subunits can result in loss of function and, potentially, underlie neurologic diseases.


Classification by gating

Ion channels may be classified by gating, i.e. what opens and closes the channels. For example, voltage-gated ion channels open or close depending on the voltage gradient across the plasma membrane, while ligand-gated ion channels open or close depending on binding of
ligands In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electron pairs ...
to the channel.


Voltage-gated

Voltage-gated ion channels open and close in response to
membrane potential 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 the amount of wo ...

membrane potential
. * Voltage-gated sodium channels: This family contains at least 9 members and is largely responsible for
action potential In physiology, an action potential (AP) occurs when the membrane potential of a specific Cell (biology), cell location rapidly rises and falls: this depolarization then causes adjacent locations to similarly depolarize. Action potentials occur ...

action potential
creation and propagation. The pore-forming α subunits are very large (up to 4,000
amino acid Amino acids are organic compound , CH4; is among the simplest organic compounds. In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen chemical bond, bonds. Due to carbon's ability to Catenation, c ...

amino acid
s) and consist of four homologous repeat domains (I-IV) each comprising six transmembrane segments (S1-S6) for a total of 24 transmembrane segments. The members of this family also coassemble with auxiliary β subunits, each spanning the membrane once. Both α and β subunits are extensively
glycosylated Glycosylation (see also chemical glycosylation) is the reaction in which a carbohydrate (or 'glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconj ...

glycosylated
. *
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, neuron A neuron or nerve ...
s: This family contains 10 members, though these are known to coassemble with α2δ, β, and γ subunits. These channels play an important role in both linking muscle excitation with contraction as well as neuronal excitation with transmitter release. The α subunits have an overall structural resemblance to those of the sodium channels and are equally large. ** Cation channels of sperm: This small family of channels, normally referred to as Catsper channels, is related to the two-pore channels and distantly related to TRP channels. *
Voltage-gated potassium channel Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell ...
s (KV): This family contains almost 40 members, which are further divided into 12 subfamilies. These channels are known mainly for their role in repolarizing the cell membrane following
action potential In physiology, an action potential (AP) occurs when the membrane potential of a specific Cell (biology), cell location rapidly rises and falls: this depolarization then causes adjacent locations to similarly depolarize. Action potentials occur ...

action potential
s. The α subunits have six transmembrane segments, homologous to a single domain of the sodium channels. Correspondingly, they assemble as
tetramer A tetramer () (''tetra- Numeral or number prefixes are prefix A prefix is an affix which is placed before the stem of a word. Adding it to the beginning of one word changes it into another word. For example, when the prefix ''un-'' is added to t ...
s to produce a functioning channel. *Some
transient receptor potential channel Transient receptor potential channels (TRP channels) are a group of s located mostly on the of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes ( "C" for canonical), ("V" for vanilloid), ("VL" for v ...
s: This group of channels, normally referred to simply as TRP channels, is named after their role in
Drosophila ''Drosophila'' () is a genus of fly, flies, belonging to the family (biology), family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the character ...

Drosophila
phototransduction. This family, containing at least 28 members, is incredibly diverse in its method of activation. Some TRP channels seem to be constitutively open, while others are gated by
voltage Voltage, electric potential difference, electric pressure or electric tension is the difference in electric potential The electric potential (also called the ''electric field potential'', potential drop, the electrostatic potential) is the ...
, intracellular Ca2+, pH, redox state, osmolarity, and mechanical stretch. These channels also vary according to the ion(s) they pass, some being selective for Ca2+ while others are less selective, acting as cation channels. This family is subdivided into 6 subfamilies based on homology: classical ( TRPC), vanilloid receptors (
TRPV TRPV is a family of transient receptor potential Transient receptor potential channels (TRP channels) are a group of ion channel s (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - ...
), melastatin (
TRPMTRPM is a family of transient receptor potential ion channel s (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane. Ion channels are pore-formin ...
), polycystins ( TRPP), mucolipins ( TRPML), and ankyrin transmembrane protein 1 ( TRPA). *Hyperpolarization-activated cyclic nucleotide-gated channels: The opening of these channels is due to hyperpolarization rather than the depolarization required for other cyclic nucleotide-gated channels. These channels are also sensitive to the cyclic nucleotides
cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to describ ...
and cGMP, which alter the voltage sensitivity of the channel's opening. These channels are permeable to the monovalent cations K+ and Na+. There are 4 members of this family, all of which form tetramers of six-transmembrane α subunits. As these channels open under hyperpolarizing conditions, they function as pacemaking channels in the heart, particularly the
SA node The sinoatrial node (also known as the sinuatrial node, SA node or sinus node) is a group of cells located in the wall of the right atrium of the heart The heart is a muscle, muscular Organ (anatomy), organ in most animals, which pumps bl ...
. * Voltage-gated proton channels: Voltage-gated proton channels open with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when the electrochemical gradient is outward, such that their opening will only allow protons to leave cells. Their function thus appears to be acid extrusion from cells. Another important function occurs in phagocytes (e.g.
eosinophils Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a network of ...
,
neutrophils Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...

neutrophils
,
macrophages Macrophages (abbreviated as MPhi, φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests anything that does not hav ...
) during the "respiratory burst." When bacteria or other microbes are engulfed by phagocytes, the enzyme
NADPH oxidase NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) is a membrane-bound enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes ...
assembles in the membrane and begins to produce
reactive oxygen species Reactive oxygen species (ROS) are highly chemicals formed from O2. Examples of ROS include s, , , , and . The reduction of molecular oxygen (O2) produces (•), which is the to most other reactive oxygen species: :O2 + e− → • of super ...
(ROS) that help kill bacteria. NADPH oxidase is electrogenic, moving electrons across the membrane, and proton channels open to allow proton flux to balance the electron movement electrically.


Ligand-gated (neurotransmitter)

Also known as ionotropic
receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ne ...

receptors
, this group of channels open in response to specific ligand molecules binding to the extracellular domain of the receptor protein. Ligand binding causes a conformational change in the structure of the channel protein that ultimately leads to the opening of the channel gate and subsequent ion flux across the plasma membrane. Examples of such channels include the cation-permeable "nicotinic" Acetylcholine receptor, ionotropic glutamate-gated receptors, acid sensing ion channels (
ASICs is a Japan, Japanese multinational corporation which produces sports equipment designed for a wide range of sports. The name is an acronym for the Latin phrase ''Mens sana in corpore sano, anima sana in corpore sano'', which translates as "Heal ...
), ATP-gated P2X receptors, and the anion-permeable γ-aminobutyric acid-gated GABAA receptor. Ion channels activated by second messengers may also be categorized in this group, although
ligands In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electron pairs ...
and second messengers are otherwise distinguished from each other.


Lipid-gated

This group of channels opens in response to specific
lipid In and , a lipid is a macro that is soluble in solvents. are typically s used to dissolve other naturally occurring hydrocarbon lipid s that do not (or do not easily) dissolve in water, including s, es, s, fat-soluble s (such as vitamins A, ...
molecules binding to the channel's transmembrane domain typically near the inner leaflet of the plasma membrane. Phosphatidylinositol 4,5-bisphosphate ( PIP2) and phosphatidic acid () are the best-characterized lipids to gate these channels. Many of the leak potassium channels are gated by lipids including the inward-rectifier potassium channels and two pore domain potassium channels TREK-1 and TRAAK. KCNQ potassium channel family are gated by PIP2. The voltage activated potassium channel (Kv) is regulated by PA. Its midpoint of activation shifts +50 mV upon PA hydrolysis, near resting membrane potentials. This suggests Kv could be opened by lipid hydrolysis independent of voltage and may qualify this channel as dual lipid and voltage gated channel.


Other gating

Gating also includes activation and inactivation by
second messenger Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intracellular signals, a non-local form or cell signaling In biology Biology is ...
s from the inside of the
cell membrane cell membrane vs. Prokaryotes A prokaryote is a typically unicellular organism that lacks a nuclear membrane-enclosed cell nucleus, nucleus. The word ''prokaryote'' comes from the Greek language, Greek (, 'before') and (, 'nut' or 'kernel').C ...

cell membrane
– rather than from outside the cell, as in the case for ligands. *Some potassium channels: ** Inward-rectifier potassium channels: These channels allow potassium ions to flow into the cell in an "inwardly rectifying" manner: potassium flows more efficiently into than out of the cell. This family is composed of 15 official and 1 unofficial member and is further subdivided into 7 subfamilies based on homology. These channels are affected by intracellular
ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals * American Technical Publishers * ', a Danish pension * Armenia Tree Project * Association for Transpersonal Psychology * ATP architects engineers office * ATP ...

ATP
, PIP2, and
G-protein 180px, Guanosine triphosphate G proteins, also known as guanine nucleotide-binding proteins, are a Protein family, family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stim ...

G-protein
βγ subunits. They are involved in important physiological processes such as pacemaker activity in the heart, insulin release, and potassium uptake in
glial cells Glia, also called glial cells (singular ''gliocyte'') or neuroglia, are non-neuronal cell (biology), cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They main ...

glial cells
. They contain only two transmembrane segments, corresponding to the core pore-forming segments of the KV and KCa channels. Their α subunits form tetramers. **
Calcium-activated potassium channel Calcium-activated potassium channels are potassium channels gated by calcium, or that are structurally or phylogenetically related to calcium gated channels. They were first discovered in 1958 by Gardos who saw that Calcium levels inside of a cell c ...
s: This family of channels is activated by intracellular Ca2+ and contains 8 members. **
Tandem pore domain potassium 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 Rectification has the following technical meanings: Mathe ...
: This family of 15 members form what are known as leak channels, and they display Goldman-Hodgkin-Katz (open)
rectification Rectification has the following technical meanings: Mathematics * Rectification (geometry), truncating a polytope by marking the midpoints of all its edges, and cutting off its vertices at those points * Rectifiable curve, in mathematics * Rectif ...

rectification
. Contrary to their common name of 'Two-pore-domain potassium channels', these channels have only one pore but two pore domains per subunit. * Two-pore channels include ligand-gated and voltage-gated cation channels, so-named because they contain two pore-forming subunits. As their name suggests, they have two pores. * Light-gated channels like channelrhodopsin are directly opened by
photon The photon ( el, φῶς, phōs, light) is a type of elementary particle In , an elementary particle or fundamental particle is a that is not composed of other particles. Particles currently thought to be elementary include the fundamental s ...

photon
s. *
Mechanosensitive ion channelMechanosensitive channels, mechanosensitive ion channels or stretch-gated ion channels (not to be confused with mechanoreceptors). They are present in the membranes of organisms from the three domains of life: bacteria, archaea, and eukarya. They ar ...
s open under the influence of stretch, pressure, shear, and displacement. * Cyclic nucleotide-gated channels: This superfamily of channels contains two families: the cyclic nucleotide-gated (CNG) channels and the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. This grouping is functional rather than evolutionary. **Cyclic nucleotide-gated channels: This family of channels is characterized by activation by either intracellular
cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to describ ...
or cGMP. These channels are primarily permeable to monovalent cations such as K+ and Na+. They are also permeable to Ca2+, though it acts to close them. There are 6 members of this family, which is divided into 2 subfamilies. **Hyperpolarization-activated cyclic nucleotide-gated channels *Temperature-gated channels: Members of the transient receptor potential ion channel superfamily, such as
TRPV1 The transient receptor potential cation channel subfamily V member 1 (TrpV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the ''TRPV1'' gene. It was the first isolated member of th ...
or
TRPM8 Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This ...
, are opened either by hot or cold temperatures.


Classification by type of ions

*
Chloride channel Chloride channels are a superfamily of poorly understood ion channel s (typically four per channel), 2 - outer vestibule, 3 - Potassium channel#Selectivity filter, selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 ...
s: This superfamily of channels consists of approximately 13 members. They include ClCs, CLICs, Bestrophins and CFTRs. These channels are non-selective for small anions; however
chloride The chloride ion An ion () is a particle In the Outline of physical science, physical sciences, a particle (or corpuscule in older texts) is a small wikt:local, localized physical body, object to which can be ascribed several physical ...

chloride
is the most abundant anion, and hence they are known as chloride channels. *
Potassium channel are indicated by red and blue lines.Potassium channels are the most widely distributed type of ion channel s (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 ...

Potassium channel
s **
Voltage-gated potassium channel Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell ...
s e.g., Kvs, Kirs etc. **
Calcium-activated potassium channel Calcium-activated potassium channels are potassium channels gated by calcium, or that are structurally or phylogenetically related to calcium gated channels. They were first discovered in 1958 by Gardos who saw that Calcium levels inside of a cell c ...
s e.g., BKCa or MaxiK, SK, etc. ** Inward-rectifier potassium channels ** Two-pore-domain potassium channels: This family of 15 members form what is known as leak channels, and they display Goldman-Hodgkin-Katz (open)
rectification Rectification has the following technical meanings: Mathematics * Rectification (geometry), truncating a polytope by marking the midpoints of all its edges, and cutting off its vertices at those points * Rectifiable curve, in mathematics * Rectif ...

rectification
. * Sodium channels ** Voltage-gated sodium channels (NaVs) **
Epithelial sodium channel The epithelial sodium channel (short: ENaC, also: amiloride-sensitive sodium channel) is a membrane-bound ion channel s (typically four per channel), 2 - outer vestibule, 3 - Potassium channel#Selectivity filter, selectivity filter, 4 - diameter ...
s (ENaCs) *
Calcium channelA calcium channel is an ion channel s (typically four per channel), 2 - outer vestibule, 3 - Potassium channel#Selectivity filter, selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane. Ion channels are ...
s (CaVs) *Proton channels ** Voltage-gated proton channels *''Non-selective cation channels'': These non-selectively allow many types of cations, mainly Na+, K+ and Ca2+, through the channel. **Most transient receptor potential channels


Classification by cellular localization

Ion channels are also classified according to their subcellular localization. The plasma membrane accounts for around 2% of the total membrane in the cell, whereas intracellular organelles contain 98% of the cell's membrane. The major intracellular compartments are
endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle In cell biology Cell biology (also cellular biology o ...
,
Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that stud ...

Golgi apparatus
, and
mitochondria A mitochondrion (; ) is a double-membrane Image:Schematic size.jpg, up150px, Schematic of size-based membrane exclusion A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, i ...

mitochondria
. On the basis of localization, ion channels are classified as: * Plasma membrane channels **Examples: Voltage-gated potassium channels (Kv), Sodium channels (Nav), Calcium channels (Cav) and Chloride channels (ClC) * Intracellular channels, which are further classified into different organelles **
Endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle In cell biology Cell biology (also cellular biology o ...
channels: RyR, SERCA, ORAi **Mitochondrial channels: mPTP, KATP, BK, IK, CLIC5, Kv7.4 at the inner membrane and VDAC and CLIC4 as outer membrane channels.


Other classifications

Some ion channels are classified by the duration of their response to stimuli: *
Transient receptor potential channel Transient receptor potential channels (TRP channels) are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC ( "C" for canonical), TRPV ...
s: This group of channels, normally referred to simply as TRP channels, is named after their role in ''
Drosophila ''Drosophila'' () is a genus of fly, flies, belonging to the family (biology), family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the character ...

Drosophila
'' visual phototransduction. This family, containing at least 28 members, is diverse in its mechanisms of activation. Some TRP channels remain constitutively open, while others are gated by
voltage Voltage, electric potential difference, electric pressure or electric tension is the difference in electric potential The electric potential (also called the ''electric field potential'', potential drop, the electrostatic potential) is the ...
, intracellular Ca2+, ,
redox (mild reducing agent) are added to powdered potassium permanganate Potassium permanganate is an inorganic compound with the chemical formula KMnO4 and composed of potassium ion, K+ and permanganate, . It is a purplish-black crystalline salt, ...

redox
state,
osmolarityOsmotic concentration, formerly known as osmolarity, is the measure of solute concentration, defined as the number of osmoles (Osm) of solute per litre (L) of solution (osmol/L or Osm/L). The osmolarity of a solution is usually expressed as Osm/L (pr ...
, and mechanical stretch. These channels also vary according to the ion(s) they pass, some being selective for Ca2+ while others are less selective cation channels. This family is subdivided into 6 subfamilies based on homology: canonical TRP ( TRPC), vanilloid receptors (
TRPV TRPV is a family of transient receptor potential Transient receptor potential channels (TRP channels) are a group of ion channel s (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - ...
), melastatin (
TRPMTRPM is a family of transient receptor potential ion channel s (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane. Ion channels are pore-formin ...
), polycystins ( TRPP), mucolipins ( TRPML), and ankyrin transmembrane protein 1 ( TRPA).


Detailed structure

Channels differ with respect to the ion they let pass (for example, , K+, ), the ways in which they may be regulated, the number of subunits of which they are composed and other aspects of structure. Channels belonging to the largest class, which includes the voltage-gated channels that underlie the nerve impulse, consists of four subunits with six
transmembrane helices Transmembrane domain usually denotes a transmembrane segment of single alpha helix of a transmembrane protein. More broadly, a transmembrane domain is any membrane-spanning protein domain. Identification of transmembrane helices Transmembrane heli ...
each. On activation, these helices move about and open the pore. Two of these six helices are separated by a loop that lines the pore and is the primary determinant of ion selectivity and conductance in this channel class and some others. The existence and mechanism for ion selectivity was first postulated in the late 1960s by Bertil Hille and Clay Armstrong. The idea of the ionic selectivity for potassium channels was that the carbonyl oxygens of the protein backbones of the "selectivity filter" (named by Bertil Hille) could efficiently replace the water molecules that normally shield potassium ions, but that sodium ions were smaller and cannot be completely dehydrated to allow such shielding, and therefore could not pass through. This mechanism was finally confirmed when the first structure of an ion channel was elucidated. A bacterial potassium channel KcsA, consisting of just the selectivity filter, "P" loop and two transmembrane helices was used as a model to study the permeability and the selectivity of ion channels in the Mackinnon lab. The determination of the molecular structure of KcsA by
Roderick MacKinnon Roderick MacKinnon (born February 19, 1956) is an American biophysicist, neuroscientist, and businessman. He is a professor of Molecular Neurobiology and Biophysics at Rockefeller University who won the Nobel Prize in Chemistry together with Peter ...
using
X-ray crystallography X-ray crystallography (XRC) is the experimental science determining the atomic and molecular structure of a crystal A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a ...

X-ray crystallography
won a share of the 2003
Nobel Prize in Chemistry ) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "MD ...
. Because of their small size and the difficulty of crystallizing integral membrane proteins for X-ray analysis, it is only very recently that scientists have been able to directly examine what channels "look like." Particularly in cases where the crystallography required removing channels from their membranes with detergent, many researchers regard images that have been obtained as tentative. An example is the long-awaited crystal structure of a voltage-gated potassium channel, which was reported in May 2003. One inevitable ambiguity about these structures relates to the strong evidence that channels change conformation as they operate (they open and close, for example), such that the structure in the crystal could represent any one of these operational states. Most of what researchers have deduced about channel operation so far they have established through
electrophysiology Electrophysiology (from Greek , ''ēlektron'', "amber" etymology of "electron"">Electron#Etymology">etymology of "electron" , ''physis'', "nature, origin"; and , '' -logia'') is the branch of physiology Physiology (; ) is the scientific study ...
,
biochemistry Biochemistry or biological chemistry, is the study of es within and relating to living s. A sub-discipline of both and , biochemistry may be divided into three fields: , and . Over the last decades of the 20th century, biochemistry has beco ...

biochemistry
,
gene In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mecha ...

gene
sequence comparison and
mutagenesis Mutagenesis is a process by which the genetic information of an organism is changed by the production of a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laborat ...

mutagenesis
. Channels can have single (CLICs) to multiple transmembrane (K channels, P2X receptors, Na channels) domains which span plasma membrane to form pores. Pore can determine the selectivity of the channel. Gate can be formed either inside or outside the pore region.


Pharmacology

Chemical substances can modulate the activity of ion channels, for example by blocking or activating them.


Ion channel blockers

A variety of ion channel blockers (inorganic and organic molecules) can modulate ion channel activity and conductance. Some commonly used blockers include: *
Tetrodotoxin Tetrodotoxin (TTX) is a potent neurotoxin Neurotoxins are toxins that are destructive to nervous tissue, nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insult (medical), insultsSpenc ...

Tetrodotoxin
(TTX), used by
puffer fish Tetraodontidae is a family In human society, family (from la, familia) is a group of people related either by consanguinity (by recognized birth) or affinity (by marriage or other relationship). The purpose of families is to maintain ...

puffer fish
and some types of
newts A newt is a salamander Salamanders are a group of amphibians typically characterized by a lizard Lizards are a widespread group of Squamata, squamate reptiles, with over 6,000 species, ranging across all continents except Antarctica, ...
for defense. It blocks sodium channels. *
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 ...

Saxitoxin
is produced by a
dinoflagellate The dinoflagellates (Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approximately 10.7 m ...
also known as "
red tide A red tide is a phenomenon of discoloration of sea surface. It is a common name for Harmful algal bloom, harmful algal blooms occurring along coastal regions, which result from large concentrations of aquatic microorganisms, such as protozoans a ...

red tide
". It blocks voltage-dependent sodium channels. *
Conotoxin A conotoxin is one of a group of neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central nervous system, central and/or peripheral n ...
is used by
cone snails Cone snails, cone shells, or cones are a large group of small- to large-sized extremely venom Venom is a type of poison, especially one secreted by an animal. Venom has evolved in a wide variety of animals, both predators and prey, and both ...
to hunt prey. *
Lidocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates ...

Lidocaine
and
Novocaine Procaine is a local anesthetic drug of the amino esters, amino ester group. It is most commonly used in dentistry, dental procedures to numb the area around a tooth and is also used to reduce the pain of intramuscular injection of penicillin. Ow ...
belong to a class of
local anesthetics A local anesthetic (LA) is a medication that causes absence of pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotio ...
which block sodium ion channels. * Dendrotoxin is produced by
mamba Mambas are fast moving venomous snake Venomous snakes are species In biology, a species is the basic unit of biological classification, classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is of ...

mamba
snakes Snakes are elongated, limbless, carnivorous A carnivore , meaning "meat Meat is animal flesh that is eaten as food. Humans have hunted and killed animals for meat since prehistoric times. The advent of civilization allowed the domes ...

snakes
, and blocks potassium channels. * Iberiotoxin is produced by the ''
Hottentotta tamulus ''Hottentotta tamulus'', the Indian red scorpion, also known as the eastern Indian scorpion, is a species of Scorpiones, scorpion of the family Buthidae. It occurs in most of India, eastern Pakistan and the eastern lowlands of Nepal, and recently ...

Hottentotta tamulus
'' (Eastern Indian scorpion) and blocks potassium channels. * Heteropodatoxin is produced by ''
Heteropoda venatoria ''Heteropoda venatoria'' is a species of spider in the family huntsman spider, Sparassidae, the huntsman spiders. It is native to the tropics, tropical regions of the world, and it is present in some subtropics, subtropical areas as an introduced s ...

Heteropoda venatoria
'' (brown huntsman spider or laya) and blocks potassium channels.


Ion channel activators

Several compounds are known to promote the opening or activation of specific ion channels. These are classified by the channel on which they act: * Calcium channel openers, such as *
Chloride channel opener A chloride channel opener is a type of drug which facilitates ion transmission through chloride channels. An example is 1,10-phenanthroline, which activates Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. GABA-A rece ...
s, such as
phenanthroline Phenanthroline (phen) is a heterocyclic 125px, Pyridine, a heterocyclic compound A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different chemical element, elements as members of its ring(s). Hete ...
*
Potassium channel opener Potassium is a chemical element Image:Simple Periodic Table Chart-blocks.svg, 400px, Periodic table, The periodic table of the chemical elements In chemistry, an element is a pure substance consisting only of atoms that all have the same ...
s, such as
minoxidil Minoxidil (2,4-diamino-6-piperidinopyrimidine 3-oxide), sold under the brand name Rogaine among others, is a medication used for the treatment of Hypertension, high blood pressure and male-pattern hair loss, pattern hair loss in males and females ...

minoxidil
* Sodium channel openers, such as
DDT Dichlorodiphenyltrichloroethane, commonly known as DDT, is a colorless, tasteless, and almost odorless Crystallinity, crystalline chemical compound, an organochloride. Originally developed as an insecticide, it became infamous for its environmen ...

DDT


Diseases

There are a number of disorders which disrupt normal functioning of ion channels and have disastrous consequences for the organism. Genetic and autoimmune disorders of ion channels and their modifiers are known as
channelopathies Channelopathies are diseases caused by disturbed function of ion channel subunits or the proteins that regulate them. These diseases may be either congenital (often resulting from a mutation or mutations in the encoding genes) or acquired (often re ...
. See :Channelopathies for a full list. *
Shaker gene The ''shaker (Sh)'' gene, when mutated, causes a variety of atypical behaviors in the fruit fly, ''Drosophila melanogaster''. Under diethyl ether, ether anesthesia, the fly’s legs will shake (hence the name); even when the fly is unanaesthetized ...
mutations cause a defect in the voltage gated ion channels, slowing down the repolarization of the cell. * Equine hyperkalaemic periodic paralysis as well as human hyperkalaemic periodic paralysis (HyperPP) are caused by a defect in voltage-dependent sodium channels. *
Paramyotonia congenita Paramyotonia congenita (PC), is a rare congenital autosomal dominant neuromuscular disorder characterized by “paradoxical” myotonia. This type of myotonia has been termed paradoxical because it becomes worse with exercise whereas classical myot ...
(PC) and potassium-aggravated myotonias (PAM) * Generalized epilepsy with febrile seizures plus (GEFS+) *
Episodic ataxia Episodic ataxia (EA) is an autosomal dominant disorder characterized by sporadic bouts of ataxia (severe discoordination) with or without myokymia (continuous muscle movement). There are seven types recognized but the majority are due to two recogni ...
(EA), characterized by sporadic bouts of severe discoordination with or without
myokymia Myokymia is an involuntary, spontaneous, localized quivering of a few muscles, or bundles within a muscle, but which are insufficient to move a joint A joint or articulation (or articular surface) is the connection made between bone A bone ...
, and can be provoked by stress, startle, or heavy exertion such as exercise. * Familial hemiplegic migraine (FHM) * Spinocerebellar ataxia type 13 *
Long QT syndrome Long QT syndrome (LQTS) is a condition in which repolarization of the heart The heart is a muscle, muscular Organ (anatomy), organ in most animals, which pumps blood through the blood vessels of the circulatory system. The pumped blood car ...
is a ventricular
arrhythmia Arrhythmia, also known as cardiac arrhythmia or heart arrhythmia, is a group of conditions in which the is irregular, too fast, or too slow. The that is too fast – above 100 beats per minute in adults – is called , and a heart rate that i ...
syndrome A syndrome is a set of medical signs and symptoms Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, rais ...
caused by
mutation In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechan ...
s in one or more of presently ten different
gene In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mecha ...

gene
s, most of which are
potassium channel are indicated by red and blue lines.Potassium channels are the most widely distributed type of ion channel s (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 ...

potassium channel
s and all of which affect cardiac
repolarization In neuroscience Neuroscience is the science, scientific study of the nervous system. It is a Multidisciplinary approach, multidisciplinary science that combines physiology, anatomy, molecular biology, developmental biology, cytology, computer sc ...
. *
Brugada syndrome Brugada syndrome (BrS) is a genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene In biology, a gene (from ''genos'' "...Wilhelm Jo ...
is another ventricular arrhythmia caused by voltage-gated sodium channel gene mutations. *
Polymicrogyria Polymicrogyria (PMG) is a condition that affects the development of the human brain A brain is an organ (anatomy), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, ...

Polymicrogyria
is a developmental brain malformation caused by voltage-gated sodium channel and
NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in Neuron, neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being A ...

NMDA receptor
gene mutations. *
Cystic fibrosis Cystic fibrosis (CF) is a genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene In biology, a gene (from ''genos'' "...Wilhelm Johan ...
is caused by mutations in the CFTR gene, which is a chloride channel. *
Mucolipidosis type IV Mucolipidosis type IV (ML IV, ganglioside sialidase deficiency, or ML4) is an autosomal recessive lysosomal storage disorder. Individuals with the disorder have many symptoms including delayed psychomotor development and various ocular aberratio ...
is caused by mutations in the gene encoding the TRPML1 channel * Mutations in and overexpression of ion channels are important events in cancer cells. In
Glioblastoma multiforme Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive type of cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or Metastasis, spread to other parts of the body. Th ...

Glioblastoma multiforme
, upregulation of gBK potassium channels and ClC-3 chloride channels enables glioblastoma cells to migrate within the brain, which may lead to the diffuse growth patterns of these tumors.


History

The fundamental properties of currents mediated by ion channels were analyzed by the British
biophysicist uses protein domain dynamics on nanoscales to walk along a microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to Eukaryote, eukaryotic cells. Microtubules can grow as long as 50&n ...
s
Alan Hodgkin Sir Alan Lloyd Hodgkin (5 February 1914 – 20 December 1998) was an English physiology, physiologist and biophysics, biophysicist who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles (neurophysiologist), ...
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 graduating from Westminster School in Central London, from where he won a scholarship ...
as part of their
Nobel Prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel Alfred Bernhard Nobel ( , ; 21 October 1833 – 10 December 1896) was a Swedish chemist, engineer, inventor, busines ...
-winning research on the
action potential In physiology, an action potential (AP) occurs when the membrane potential of a specific Cell (biology), cell location rapidly rises and falls: this depolarization then causes adjacent locations to similarly depolarize. Action potentials occur ...

action potential
, published in 1952. They built on the work of other physiologists, such as Cole and Baker's research into voltage-gated membrane pores from 1941. The existence of ion channels was confirmed in the 1970s by
Bernard Katz Sir Bernard Katz, FRS (26 March 1911 – 20 April 2003) was a German-born British physician and biophysicist, noted for his work on nerve physiology. He shared the Nobel Prize in physiology or medicine in 1970 with Julius Axelrod and Ulf ...
and Ricardo Miledi using noise analysis. It was then shown more directly with an electrical recording technique known as 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 ...

patch clamp
", which led to a Nobel Prize to
Erwin Neher Erwin Neher (; ; born 20 March 1944) is a German biophysicist, specializing in the field of cell physiology Cell physiology is the biological study of the activities that take place in a cell to keep it alive. The term ''physiology Physiolog ...
and
Bert Sakmann Bert Sakmann (born 12 June 1942) is a German cell physiologist Physiology (; ) is the scientific study of Function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a Branches of science, sub-discipline of b ...
, the technique's inventors. Hundreds if not thousands of researchers continue to pursue a more detailed understanding of how these proteins work. In recent years the development of automated patch clamp devices helped to increase significantly the throughput in ion channel screening. The Nobel Prize in Chemistry for 2003 was awarded to
Roderick MacKinnon Roderick MacKinnon (born February 19, 1956) is an American biophysicist, neuroscientist, and businessman. He is a professor of Molecular Neurobiology and Biophysics at Rockefeller University who won the Nobel Prize in Chemistry together with Peter ...
for his studies on the physico-chemical properties of ion channel structure and function, including
structure A structure is an arrangement and organization of interrelated elements in a material object or system A system is a group of Interaction, interacting or interrelated elements that act according to a set of rules to form a unified whole. A ...

structure
studies.


Culture

Roderick MacKinnon Roderick MacKinnon (born February 19, 1956) is an American biophysicist, neuroscientist, and businessman. He is a professor of Molecular Neurobiology and Biophysics at Rockefeller University who won the Nobel Prize in Chemistry together with Peter ...
commissioned ''Birth of an Idea'', a tall sculpture based on the
KcsA potassium channelKcsA (K channel of streptomyces A) is a prokaryotic potassium channel from the soil bacteria Streptomyces, ''Streptomyces lividans'' that has been studied extensively in ion channel research. The pH activated protein possesses two transmembrane segm ...
. The artwork contains a wire object representing the channel's interior with a blown glass object representing the main cavity of the channel structure.


See also

*
Alpha helix The alpha helix (α-helix) is a common motif Motif may refer to: General concepts * Motif (chess composition), an element of a move in the consideration of its purpose * Motif (folkloristics), a recurring element that creates recognizable patte ...

Alpha helix
* Ion channel family as defined in
Pfam Pfam is a database of protein families A protein family is a group of evolutionarily-related proteins. In many cases a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. Th ...
and
InterPro InterPro is a database of protein families, domains and functional sites in which identifiable features found in known proteins can be applied to new protein sequences in order to functionally characterise them. The contents of InterPro consist of ...
* Ki Database * Lipid bilayer ion channels * Magnesium transport *
Neurotoxin Neurotoxins are toxins that are destructive to nervous tissue, nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insult (medical), insultsSpencer 2000 that can adversely affect function in ...
*
Passive transport Passive transport is a type of membrane transport that does not require energy In physics Physics (from grc, φυσική (ἐπιστήμη), physikḗ (epistḗmē), knowledge of nature, from ''phýsis'' 'nature'), , is the na ...
* Synthetic ion channels *
Transmembrane receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor ...

Transmembrane receptor


References


External links

* * * {{Authority control Cell communication Electrophysiology Integral membrane proteins Neurochemistry
Protein families This category collects together articles describing sets of related proteins Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by M ...