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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 ...
s that allow
ions 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 ...
to pass through the channel pore. Their functions include establishing a
resting membrane 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 ...
, shaping
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, ...
s and other electrical signals by gating the flow 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 conve ...
s across the
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
, controlling the flow of ions across secretory and
epithelial cell 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 ...
s, and regulating
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 ...
volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being
ion transporter In biology, a transporter is a transmembrane protein that moves ions (or other small molecules) across a biological membrane to accomplish many different biological functions including, cellular communication, maintaining homeostasis, energy produ ...
s. The study of ion channels often involves
biophysics Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study biological phenomena. Biophysics covers all scales of biological organization, from molecular to organismic and populations. ...
,
electrophysiology Electrophysiology (from Greek , ''ēlektron'', "amber" etymology of "electron"">Electron#Etymology">etymology of "electron" , ''physis'', "nature, origin"; and , '' -logia'') is the branch of physiology that studies the electrical properties of b ...
, and
pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...
, while using techniques including
voltage clamp The voltage clamp is an experimental method used by electrophysiologists to measure the ion currents through the membranes of excitable cells, such as neurons, while holding the membrane voltage at a set level. A basic voltage clamp will iterativ ...
,
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 ...
,
immunohistochemistry Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to an ...
,
X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
,
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 imaging, a fluoroscope () allows a physician to see the internal structure and functio ...
, 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 cha ...
. Their classification as molecules is referred to as
channelomics The channelome, sometimes called the "ion channelome", is the complete set of ion channelsDoyle, D. A., Morais-Cabral, J., Pfuetzner, R. A., Kuo, A, Gulbis, JM, Cohen, SL, Chait, BT, MacKinnon, R (1998) The structure of the potassium channel: molecu ...
.


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 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 ...
, which is a function of ion concentration and membrane potential, "downhill", without the input (or help) of metabolic energy (e.g. ATP,
co-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 ...
mechanisms, or
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 ...
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. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
of all excitable cells, and of many intracellular
organelle In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
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 Semipermeable membrane is a type of biological or synthetic, polymeric membrane that will allow certain molecules or ions to pass through it by osmosis. The rate of passage depends on the pressure, concentration, and temperature of the molecul ...
. 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 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 ...
or
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 ...
. 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 or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
s) or negative (
anion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
s). Ions often move through the segments of the channel pore in a single file nearly as quickly as the ions move through the 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, 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, 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 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 ...
. For most
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, 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 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, c ...
and because "transmitter-activated" channels mediate conduction across the
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, channels are especially prominent components of the
nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
. 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 muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...
,
skeletal A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...
, and
smooth muscle Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
contraction Contraction may refer to: Linguistics * Contraction (grammar), a shortened word * Poetic contraction, omission of letters for poetic reasons * Elision, omission of sounds ** Syncope (phonology), omission of sounds in a word * Synalepha, merged ...
,
epithelial 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 ...
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 distinguished from other lymphocytes by the presence of a T-cell rec ...
activation, and
pancreatic The pancreas is an Organ (anatomy), organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine ...
beta-cell
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
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 metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electro ...
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 between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges ...
. *
Voltage-gated sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
s: This family contains at least 9 members and is largely responsible for
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, ...
creation and propagation. The pore-forming α subunits are very large (up to 4,000
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
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 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 glycoconjugate. In biology (but not alw ...
. *
Voltage-gated calcium channel Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeabi ...
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 The cation channels of sperm also known as Catsper channels or CatSper, are ion channels that are related to the two-pore channels and distantly related to TRP channels. The four members of this family form voltage-gated Ca2+ channels that ...
: This small family of channels, normally referred to as Catsper channels, is related to the
two-pore channels Two-pore channels (TPCs) are eukaryotic intracellular voltage-gated and ligand gated cation selective ion channels. There are two known paralogs in the human genome, TPC1s and TPC2s. In humans, TPC1s are sodium selective and TPC2s conduct so ...
and distantly related to
TRP channels 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), T ...
. *
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 ce ...
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 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, ...
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-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula Ti ...
s to produce a functioning channel. *Some
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), TR ...
s: This group of channels, normally referred to simply as TRP channels, is named after their role in
Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
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, also known as electric pressure, electric tension, or (electric) potential difference, is the difference in electric potential between two points. In a static electric field, it corresponds to the work needed per unit of charge to m ...
, 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 TRPC is a family of transient receptor potential cation channels in animals. TRPC channels form the subfamily of channels in humans most closely related to drosophila TRP channels. Structurally, members of this family possess a number of similar ...
), vanilloid receptors (
TRPV TRPV is a family of transient receptor potential cation channels (TRP channels) in animals. All TRPVs are highly calcium selective. TRP channels are a large group of ion channels consisting of six protein families, located mostly on the plasma ...
), melastatin (
TRPM TRPM is a family of transient receptor potential ion channels (''M'' standing for '' wikt:melastatin''). Functional TRPM channels are believed to form tetramers. The TRPM family consists of eight different channels, TRPM1–TRPM8. Unlike the TRPC ...
), polycystins (
TRPP TRPP (transient receptor potential polycystic) is a family of transient receptor potential ion channels which when mutated can cause polycystic kidney disease. Subcategories TRPP subunits can be divided into two subcategories depending on structu ...
), mucolipins (
TRPML TRPML (transient receptor potential cation channel, mucolipin subfamily) comprises a group of three evolutionarily related proteins that belongs to the large family of transient receptor potential ion channels. The three proteins TRPML1, TRPML2 ...
), and ankyrin transmembrane protein 1 ( TRPA). *Hyperpolarization-activated
cyclic nucleotide-gated channel Cycle, cycles, or cyclic may refer to: Anthropology and social sciences * Cyclic history, a theory of history * Cyclical theory, a theory of American political history associated with Arthur Schlesinger, Sr. * Social cycle, various cycles in so ...
s: 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 descri ...
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 an oval shaped region of special cardiac muscle in the upper back wall of the right atrium made up of cells known as pacemaker cells. The sinus node is approximat ...
. *
Voltage-gated proton channel Voltage-gated proton channels are ion channels that have the unique property of opening with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when the electrochemical gradient is outward, such tha ...
s: 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 cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
,
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 ...
,
macrophages Macrophages (abbreviated as M 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 pathogens, such as cancer ce ...
) 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 complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white ...
assembles in the membrane and begins to produce
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...
(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 n ...
, 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), 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 metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electro ...
and second messengers are otherwise distinguished from each other.


Lipid-gated

This group of channels opens in response to specific
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
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 ( PA) 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. (Intercellular signals, a non-local form or cell signaling, encompassing both first me ...
s from the inside of the
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
– 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, PIP2, and
G-protein G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...
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 (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myel ...
. 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 ...
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. These channels are regulated by several mechanisms including ...
: This family of 15 members form what are known as
leak 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, and they display Goldman-Hodgkin-Katz (open) 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 channel Two-pore channels (TPCs) are eukaryotic intracellular voltage-gated and ligand gated cation selective ion channels. There are two known paralogs in the human genome, TPC1s and TPC2s. In humans, TPC1s are sodium selective and TPC2s conduct so ...
s 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 Channelrhodopsins are a subfamily of retinylidene proteins ( rhodopsins) that function as light-gated ion channels. They serve as sensory photoreceptors in unicellular green algae, controlling phototaxis: movement in response to light. Express ...
are directly opened by
photon A photon () is an elementary particle that is a quantum of the electromagnetic field, including electromagnetic radiation such as light and radio waves, and the force carrier for the electromagnetic force. Photons are massless, so they always ...
s. *
Mechanosensitive ion channel Mechanosensitive 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 ...
s open under the influence of stretch, pressure, shear, and displacement. *
Cyclic nucleotide-gated channels Cycle, cycles, or cyclic may refer to: Anthropology and social sciences * Cyclic history, a theory of history * Cyclical theory, a theory of American political history associated with Arthur Schlesinger, Sr. * Social cycle, various cycles in so ...
: 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 descri ...
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 Cycle, cycles, or cyclic may refer to: Anthropology and social sciences * Cyclic history, a theory of history * Cyclical theory, a theory of American political history associated with Arthur Schlesinger, Sr. * Social cycle, various cycles in so ...
*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 that in humans is encoded by the ''TRPM8'' gene. The TRPM8 channel is the primary molecular ...
, are opened either by hot or cold temperatures.


Classification by type of ions

*
Chloride channel Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration ''in vivo'' is much higher than other anions. Severa ...
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 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 ...
is the most abundant anion, and hence they are known as chloride channels. *
Potassium channel Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cel ...
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 ce ...
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 ...
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 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, and they display Goldman-Hodgkin-Katz (open) rectification. *
Sodium channels Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the chann ...
**
Voltage-gated sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
s (NaVs) ** Epithelial sodium channels (ENaCs) *
Calcium channel A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels. Comparison tables The following tables e ...
s (CaVs) *Proton channels **
Voltage-gated proton channels Voltage-gated proton channels are ion channels that have the unique property of opening with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when the electrochemical gradient is outward, such tha ...
*''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 made up of two subunits – rough endoplasmic reticulum ( ...
,
Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...
, and
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 ...
. 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 made up of two subunits – rough endoplasmic reticulum ( ...
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), TR ...
s: This group of channels, normally referred to simply as TRP channels, is named after their role in ''
Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
'' 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, also known as electric pressure, electric tension, or (electric) potential difference, is the difference in electric potential between two points. In a static electric field, it corresponds to the work needed per unit of charge to m ...
, intracellular Ca2+, pH,
redox Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate (chemistry), substrate change. Oxidation is the loss of Electron, electrons or an increase in the oxidation state, while reduction ...
state,
osmolarity Osmotic 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 ...
, 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 TRPC is a family of transient receptor potential cation channels in animals. TRPC channels form the subfamily of channels in humans most closely related to drosophila TRP channels. Structurally, members of this family possess a number of similar ...
), vanilloid receptors (
TRPV TRPV is a family of transient receptor potential cation channels (TRP channels) in animals. All TRPVs are highly calcium selective. TRP channels are a large group of ion channels consisting of six protein families, located mostly on the plasma ...
), melastatin (
TRPM TRPM is a family of transient receptor potential ion channels (''M'' standing for '' wikt:melastatin''). Functional TRPM channels are believed to form tetramers. The TRPM family consists of eight different channels, TRPM1–TRPM8. Unlike the TRPC ...
), polycystins (
TRPP TRPP (transient receptor potential polycystic) is a family of transient receptor potential ion channels which when mutated can cause polycystic kidney disease. Subcategories TRPP subunits can be divided into two subcategories depending on structu ...
), mucolipins (
TRPML TRPML (transient receptor potential cation channel, mucolipin subfamily) comprises a group of three evolutionarily related proteins that belongs to the large family of transient receptor potential ion channels. The three proteins TRPML1, TRPML2 ...
), and ankyrin transmembrane protein 1 ( TRPA).


Detailed structure

Channels differ with respect to the ion they let pass (for example, Na+, K+, Cl), 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 A transmembrane domain (TMD) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. Because the interior of the lipid bi ...
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 Clay Margrave Armstrong (born 1934) is an American physiologist and a former student of Andrew Fielding Huxley. Armstrong received his MD from Washington University School of Medicine in 1960. He is currently emeritus professor of Physiology at t ...
. 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 is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
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 "M ...
. 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 that studies the electrical properties of b ...
,
biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
,
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
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 la ...
. 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. Its name derives from Tetraodontiformes, an order that includes pufferfish, porcupinefish, ocean sunfish, and triggerfish; several of these species carry the toxin. Although tetrodotoxin was discovered ...
(TTX), used by
puffer fish Tetraodontidae is a family of primarily marine and estuarine fish of the order Tetraodontiformes. The family includes many familiar species variously called pufferfish, puffers, balloonfish, blowfish, blowies, bubblefish, globefish, swellfish ...
and some types of
newts A newt is a salamander in the subfamily Pleurodelinae. The terrestrial juvenile phase is called an eft. Unlike other members of the family Salamandridae, newts are semiaquatic, alternating between aquatic and terrestrial habitats. Not all aqua ...
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 ...
is produced by a
dinoflagellate The dinoflagellates (Greek δῖνος ''dinos'' "whirling" and Latin ''flagellum'' "whip, scourge") are a monophyletic group of single-celled eukaryotes constituting the phylum Dinoflagellata and are usually considered algae. Dinoflagellates are ...
also known as "
red tide A harmful algal bloom (HAB) (or excessive algae growth) is an algal bloom that causes negative impacts to other organisms by production of natural phycotoxin, algae-produced toxins, mechanical damage to other organisms, or by other means. HABs are ...
". It blocks voltage-dependent sodium channels. *
Conotoxin A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus ''Conus''. Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. Cono ...
is used by
cone snails A cone is a three-dimensional geometric shape that tapers smoothly from a flat base (frequently, though not necessarily, circular) to a point called the apex or vertex. A cone is formed by a set of line segments, half-lines, or lines co ...
to hunt prey. *
Lidocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidoca ...
and
Novocaine Procaine is a local anesthetic drug of the amino ester group. It is most commonly used in dental procedures to numb the area around a tooth and is also used to reduce the pain of intramuscular injection of penicillin. Owing to the ubiquity of ...
belong to a class of
local anesthetics A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of consciousness, as opposed to a general an ...
which block sodium ion channels. *
Dendrotoxin Dendrotoxins are a class of presynaptic neurotoxins produced by mamba snakes ('' Dendroaspis'') that block particular subtypes of voltage-gated potassium channels in neurons, thereby enhancing the release of acetylcholine at neuromuscular junctio ...
is produced by
mamba Mambas are fast moving highly venomous snakes of the genus ''Dendroaspis'' (which literally means "tree asp") in the family Elapidae. Four extant species are recognised currently; three of those four species are essentially arboreal and green ...
snakes Snakes are elongated, limbless, carnivorous reptiles of the suborder Serpentes . Like all other squamates, snakes are ectothermic, amniote vertebrates covered in overlapping scales. Many species of snakes have skulls with several more joi ...
, and blocks potassium channels. *
Iberiotoxin Iberiotoxin (IbTX) is an ion channel toxin purified from the Eastern Indian red scorpion ''Hottentotta tamulus''. Iberiotoxin selectively inhibits the current through large-conductance calcium-activated potassium channels. Chemistry Iberiotoxin ...
is produced by the ''
Hottentotta tamulus ''Hottentotta tamulus'', the Indian red scorpion, also known as the eastern Indian scorpion, is a species of scorpion of the family Buthidae. It occurs in most of India, eastern Pakistan and the eastern lowlands of Nepal, and recently from Sri L ...
'' (Eastern Indian scorpion) and blocks potassium channels. *
Heteropodatoxin Heteropodatoxins are peptide toxins from the venom of the giant crab spider ''Heteropoda venatoria'', which block Kv4.2 voltage-gated potassium channels. Sources Heteropodatoxins are purified from the venom of the giant crab spider, ''Heteropoda ...
is produced by ''
Heteropoda venatoria ''Heteropoda venatoria'' is a species of spider in the family Sparassidae, the huntsman spiders. It is native to the tropical regions of the world, and it is present in some subtropical areas as an introduced species. Its common names include gi ...
'' (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 opener A calcium channel opener is a type of drug which facilitates ion transmission through calcium channels. An example is Bay K8644, which is an analogue of nifedipine that specifically and directly activates L-type voltage-dependent calcium chann ...
s, such as
Bay K8644 Bay K8644 is a chemical compound that functions as an L-type calcium channel agonist. Bay K8644 is used primarily as a biochemical research tool for this effect. It is a structural analog of nifedipine with positive inotropic activity, and as an ...
* Chloride channel openers, such as
phenanthroline 1,10-Phenanthroline (phen) is a heterocyclic organic compound. It is a white solid that is soluble in organic solvents. The 1,10 refer to the location of the nitrogen atoms that replace CH's in the hydrocarbon called phenanthrene. Abbreviated ...
*
Potassium channel opener A potassium channel opener is a type of drug which facilitates ion transmission through potassium channels. Examples Some examples include: *Diazoxide vasodilator used for hypertension, smooth muscle relaxing activity *Minoxidil vasodilator u ...
s, such as
minoxidil Minoxidil, sold under the brand name Rogaine among others, is a medication used for the treatment of high blood pressure and pattern hair loss. It is an antihypertensive vasodilator. It is available as a generic medication by prescription in or ...
*
Sodium channel opener A sodium channel opener is a type of drug which facilitates ion transmission through sodium channels. Examples include toxins, such as aconitine, veratridine, batrachotoxin, robustoxin, palytoxin and ciguatoxins and insecticides (DDT and pyrethroid ...
s, such as
DDT Dichlorodiphenyltrichloroethane, commonly known as DDT, is a colorless, tasteless, and almost odorless crystalline chemical compound, an organochloride. Originally developed as an insecticide, it became infamous for its environmental impacts. ...


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 a group of diseases caused by the dysfunction of ion channel subunits or their interacting proteins. These diseases can be inherited or acquired by other disorders, drugs, or toxins. Mutations in genes encoding ion channels, wh ...
. 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 ether anesthesia, the fly’s legs will shake (hence the name); even when the fly is unanaesthetized, it will exhi ...
mutations cause a defect in the voltage gated ion channels, slowing down the repolarization of the cell. *
Equine hyperkalaemic periodic paralysis Hyperkalemic periodic paralysis (HYPP, HyperKPP) is a genetic disorder that occurs in horses. It is also known as Impressive syndrome, after an index case in a horse named Impressive (horse), Impressive. It is an genetic disease, inherited autosom ...
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 myotonia, ...
(PC) and potassium-aggravated myotonias (PAM) *
Generalized epilepsy with febrile seizures plus Generalized epilepsy with febrile seizures plus (GEFS+) is a syndromic autosomal dominant disorder where affected individuals can exhibit numerous epilepsy phenotypes. GEFS+ can persist beyond early childhood (i.e., 6 years of age). GEFS+ is a ...
(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 recog ...
(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. One type is superior oblique myokymia. Myokymia is commonly used to describe an involuntary eye ...
, and can be provoked by stress, startle, or heavy exertion such as exercise. *
Familial hemiplegic migraine Familial hemiplegic migraine (FHM) is an autosomal dominant type of hemiplegic migraine that typically includes weakness of half the body which can last for hours, days, or weeks. It can be accompanied by other symptoms, such as ataxia, coma, ...
(FHM) *
Spinocerebellar ataxia type 13 Spinocerebellar ataxia type 13 (SCA13) is a rare autosomal dominant disorder, which, like other types of SCA, is characterized by dysarthria, nystagmus, and ataxia of gait, stance and the limbs due to cerebellar dysfunction. Patients with SCA13 ...
*
Long QT syndrome Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainting, d ...
is a ventricular
arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek σύνδρομον, meaning "concurrence". When a syndrome is paired ...
caused by
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s in one or more of presently ten different
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s, most of which are
potassium channel Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cel ...
s and all of which affect cardiac
repolarization In neuroscience, repolarization refers to the change in membrane potential that returns it to a negative value just after the depolarization phase of an action potential which has changed the membrane potential to a positive value. The repolarizat ...
. *
Brugada syndrome Brugada syndrome (BrS) is a genetic disorder in which the electrical activity of the heart is abnormal due to channelopathy. It increases the risk of abnormal heart rhythms and sudden cardiac death. Those affected may have episodes of syncope ...
is another ventricular arrhythmia caused by
voltage-gated sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
gene mutations. *
Polymicrogyria Polymicrogyria (PMG) is a condition that affects the development of the human brain by multiple small gyri ( microgyri) creating excessive folding of the brain leading to an abnormally thick cortex. This abnormality can affect either one region o ...
is a developmental brain malformation caused by
voltage-gated sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
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 neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ...
gene mutations. *
Cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...
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 aberration ...
is caused by mutations in the gene encoding the
TRPML1 Mucolipin-1 also known as TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) is a protein that in humans is encoded by the ''MCOLN1'' gene. It is a member of the small family of the TRPML channels, a subgroup of ...
channel * Mutations in and overexpression of ion channels are important events in cancer cells. In
Glioblastoma multiforme Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...
, 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 Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study Biology, biological phenomena. Biophysics covers all scales of biological organization, from Molecule, molecular to organismic ...
s
Alan Hodgkin Sir Alan Lloyd Hodgkin (5 February 1914 – 20 December 1998) was an English physiologist and biophysicist who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles. Early life and education Hodgkin was bo ...
and
Andrew Huxley Sir Andrew Fielding Huxley (22 November 191730 May 2012) was an English physiologist and biophysicist. He was born into the prominent Huxley family. After leaving Westminster School in central London, he went to Trinity College, Cambridge on ...
as part of their
Nobel Prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
-winning research on the
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, ...
, 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, Fellow of the Royal Society, FRS (; 26 March 1911 – 20 April 2003) was a German-born British people, British physician and biophysics, biophysicist, noted for his work on nerve physiology. He shared the Nobel Prize in Physiol ...
and
Ricardo Miledi Ricardo Miledi (15 September 1927 – 18 December 2017) was a Mexican neuroscientist known for his work deciphering the role of calcium in neurotransmitter release. He also helped to develop a technique for studying native receptors in frog oocyte ...
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 ...
", 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. For significant contribution in the field, in 1991 he was awarded, along with Bert Sakmann, the Nobel Prize in Physiology or Medicine for ...
and
Bert Sakmann Bert Sakmann (; born 12 June 1942) is a German cell physiologist. He shared the Nobel Prize in Physiology or Medicine with Erwin Neher in 1991 for their work on "the function of single ion channels in cells," and the invention of the patch cla ...
, 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 x-ray crystallographic
structure A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...
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 channel KcsA (K channel of streptomyces A) is a prokaryotic potassium channel from the soil bacterium ''Streptomyces lividans'' that has been studied extensively in ion channel research. The pH activated protein possesses two transmembrane segments and a ...
. 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 in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...
* Babycurus toxin 1 *
Ion channel family The transmembrane cation channel superfamily was defined in InterPro and Pfam as the family of tetrameric ion channels. These include the sodium, potassium, calcium, ryanodine receptor, HCN, CNG, CatSper, and TRP channels. This large group ...
as defined in
Pfam Pfam is a database of protein families that includes their annotations and multiple sequence alignments generated using hidden Markov models. The most recent version, Pfam 35.0, was released in November 2021 and contains 19,632 families. Uses ...
and
InterPro InterPro is a database of protein families, protein 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 ...
* Ki Database * Lipid bilayer ion channels *
Magnesium transport 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 ...
*
Neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...
*
Passive transport 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 dri ...
*
Synthetic ion channels Synthetic ion channels are ''de novo'' chemical compounds that insert into lipid bilayers, form pores, and allow ions to flow from one side to the other. They are man-made analogues of natural ion channels, and are thus also known as artificial i ...
*
Transmembrane receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptor (biochemistry), receptors that are embedded in the cell membrane, plasma membrane of cell (biology), cells. They act in cell signaling by receiving (binding to) ex ...


References


External links

* * * * {{Authority control Cell communication Electrophysiology Integral membrane proteins Neurochemistry Protein families