Editing Ion channel

{{Short description|Pore-forming membrane protein}}
{{distinguish|Ion Television|Ion implantation}}

[[Image:Ion channel.png|thumb|upright=1.3|Schematic diagram of an ion channel. '''1''' - channel [[protein domain|domain]]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 pore-forming [[membrane protein]]s that allow [[ions]] to pass through the channel pore. Their functions include establishing a [[resting membrane potential]],<ref>{{cite journal | vauthors = Abdul Kadir L, Stacey M, Barrett-Jolley R | title = Emerging Roles of the Membrane Potential: Action Beyond the Action Potential | journal = Frontiers in Physiology | volume = 9 | pages = 1661 | date = 2018 | pmid = 30519193 | doi = 10.3389/fphys.2018.01661 | pmc = 6258788 | doi-access = free }}</ref> shaping [[action potential]]s and other electrical signals by [[Gating (electrophysiology)|gating]] the flow of [[ion]]s across the [[cell membrane]], controlling the flow of ions across [[secretion|secretory]] and [[epithelial cell]]s, and regulating [[cell (biology)|cell]] volume. Ion channels are present in the membranes of all cells.<ref>{{cite journal | vauthors = Alexander SP, Mathie A, Peters JA |title = Ion Channels |journal=British Journal of Pharmacology |date=November 2011 |volume=164 |issue=Suppl 1 |pages=S137–S174 |doi=10.1111/j.1476-5381.2011.01649_5.x|pmc=3315630 }}</ref><ref name=all>{{cite web|url=https://www.nature.com/scitable/topicpage/ion-channel-14047658|title=Ion Channel|publisher=[[Scitable]]|year=2014|access-date=2019-05-28}}</ref> Ion channels are one of the two classes of [[ionophore|ionophoric]] proteins, the other being [[ion transporter]]s.<ref name="isbn978-0-87893-321-1">{{cite book | author-link1=Bertil Hille | last = Hille | first = Bertil | name-list-style = vanc | title = Ion Channels of Excitable Membranes | edition = 3rd | publisher = Sinauer Associates, Inc. | location = Sunderland, Mass | year = 2001 | orig-year = 1984 | pages = 5 | isbn = 978-0-87893-321-1 }}</ref>

The study of ion channels often involves [[biophysics]], [[electrophysiology]], and [[pharmacology]], while using techniques including [[voltage clamp]], [[patch clamp]], [[immunohistochemistry]], [[X-ray crystallography]], [[fluoroscopy]], and [[RT-PCR]]. Their classification as molecules is referred to as [[channelomics]].
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== Basic features ==
[[File:Spin 1K4C.gif|thumb|Structure of the KcsA [[potassium channel]] ([https://www.rcsb.org/3d-view/1K4C/1?preset=membrane PDB: 1K4C]). The two gray planes indicate the [[hydrocarbon]] boundaries of the [[lipid bilayer]] and were calculated with the ANVIL algorithm.<ref name="anvil">{{Cite journal|last1=Postic|first1=Guillaume|last2=Ghouzam|first2=Yassine|last3=Guiraud|first3=Vincent|last4=Gelly|first4=Jean-Christophe|date=2016|title=Membrane positioning for high- and low-resolution protein structures through a binary classification approach|journal=Protein Engineering, Design and Selection|volume=29|issue=3|pages=87–91|doi=10.1093/protein/gzv063|pmid=26685702|doi-access=free}}</ref>]]
There are two distinctive features of ion channels that differentiate them from other types of ion transporter proteins:<ref name = isbn978-0-87893-321-1 />
# The rate of ion transport through the channel is very high (often 10<sup>6</sup> ions per second or greater).
# Ions pass through channels down their [[electrochemical gradient]], which is a function of ion concentration and membrane potential, "downhill", without the input (or help) of metabolic energy (e.g. [[Adenosine triphosphate|ATP]], [[co-transport]] mechanisms, or [[active transport]] mechanisms).
Ion channels are located within the [[cell membrane|membrane]] of all excitable cells,<ref name=all/> and of many intracellular [[organelle]]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]]. 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]] or [[potassium]]. However, some channels may be permeable to the passage of more than one type of ion, typically sharing a common charge: positive ([[cation]]s) or negative ([[anion]]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.{{cn|date=August 2024}}

Ion channels are [[integral membrane protein]]s, typically formed as assemblies of several individual proteins. Such "multi-[[protein subunit|subunit]]" assemblies usually involve a circular arrangement of identical or [[homology (biology)|homologous]] proteins closely packed around a water-filled pore through the plane of the membrane or [[lipid bilayer]].<ref name="isbn978-0-87893-741-7">{{cite book | editor-link1 = Dale Purves | editor-first1 = Dale | editor-last1 = Purves | editor-first2 = George J. | editor-last2 = Augustine | editor-first3 = David | editor-last3 = Fitzpatrick | editor-link4 = Larry Katz | editor-first4 = Lawrence. C. | editor-last4 = Katz | editor-first5 = Anthony-Samuel | editor-last5 = LaMantia | editor-first6 = James O. | editor-last6 = McNamara | editor-first7 = S. Mark | editor-last7 = Williams | name-list-style = vanc | title = Neuroscience | edition = 2nd | publisher = Sinauer Associates Inc. | year = 2001 | chapter = Chapter 4: Channels and Transporters | isbn = 978-0-87893-741-7 | chapter-url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=neurosci.chapter.227 }}</ref><ref name="isbn0-397-51820-X">{{cite book | author-link1=Bertil Hille  | vauthors =  Hille B, Catterall WA | editor-first1 = George J | editor-last1 = Siegel | editor-first2 = Bernard W | editor-last2 = Agranoff | editor-first3 = R. W | editor-last3 = Albers | editor-first4 = Stephen K | editor-last4 = Fisher | editor-first5 = Michael D | editor-last5 = Uhler | name-list-style = vanc | title = Basic neurochemistry: molecular, cellular, and medical aspects | publisher = Lippincott-Raven | location = Philadelphia | year = 1999 | chapter = Chapter 6: Electrical Excitability and Ion Channels| isbn = 978-0-397-51820-3 | chapter-url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=bnchm.chapter.421 }}</ref> For most [[voltage-gated ion channel]]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]] and because "transmitter-activated" channels mediate conduction across the [[synapse]]s, channels are especially prominent components of the [[nervous system]]. Indeed, [[#Ion channel blockers|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 muscle|cardiac]], [[skeletal muscle|skeletal]], and [[smooth muscle]] [[Muscle contraction|contraction]], [[epithelium|epithelial]] transport of nutrients and ions, [[T-cell]] activation, and [[pancreas|pancreatic]] beta-cell [[insulin]] release. In the search for new drugs, ion channels are a frequent target.<ref name="pmid17395128">{{cite journal | vauthors = Camerino DC, Tricarico D, Desaphy JF | title = Ion channel pharmacology | journal = Neurotherapeutics | volume = 4 | issue = 2 | pages = 184–98 | date = April 2007 | pmid = 17395128 | doi = 10.1016/j.nurt.2007.01.013 | doi-access = free }}</ref><ref name="pmid19153558">{{cite journal | vauthors = Verkman AS, Galietta LJ | title = Chloride channels as drug targets | journal = Nature Reviews. Drug Discovery | volume = 8 | issue = 2 | pages = 153–71 | date = February 2009 | pmid = 19153558 | pmc = 3601949 | doi = 10.1038/nrd2780 }}</ref><ref name="pmid19161833">{{cite book | vauthors = Camerino DC, Desaphy JF, Tricarico D, Pierno S, Liantonio A | title = Therapeutic Approaches to Ion Channel Diseases | volume = 64 | pages = 81–145 | year = 2008 | pmid = 19161833 | doi = 10.1016/S0065-2660(08)00804-3 | isbn = 978-0-12-374621-4 | series = Advances in Genetics }}</ref>

==Diversity==

There are over 300 types of ion channels just in the cells of the inner ear.<ref name="pmid17541769">{{cite journal | vauthors = Gabashvili IS, Sokolowski BH, Morton CC, Giersch AB | title = Ion channel gene expression in the inner ear | journal = Journal of the Association for Research in Otolaryngology | volume = 8 | issue = 3 | pages = 305–28 | date = September 2007 | pmid = 17541769 | pmc = 2538437 | doi = 10.1007/s10162-007-0082-y }}</ref> Ion channels may be classified by the nature of their [[Gating (electrophysiology)|gating]], the species of ions passing through those gates, the number of gates (pores), and localization of proteins.<ref>{{cite web |url=https://www.ionchannellibrary.com/classification-of-ion-channels/ |access-date=October 6, 2024 |title=Classification of ion channels — Ion Channel Library}}</ref>

Further heterogeneity of ion channels arises when channels with different constitutive [[Protein subunit|subunits]] give rise to a specific kind of current.<ref>{{cite journal | vauthors = Vicini S | title = New perspectives in the functional role of GABA(A) channel heterogeneity | journal = Molecular Neurobiology | volume = 19 | issue = 2 | pages = 97–110 | date = April 1999 | pmid = 10371465 | doi = 10.1007/BF02743656 | s2cid = 5832189 }}</ref> 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.<ref>{{Cite journal |last=Eijkelkamp |first=N. |last2=Linley |first2=J. E. |last3=Baker |first3=M. D. |last4=Minett |first4=M. S. |last5=Cregg |first5=R. |last6=Werdehausen |first6=R. |last7=Rugiero |first7=F. |last8=Wood |first8=J. N. |date=2012-09-01 |title=Neurological perspectives on voltage-gated sodium channels |url=https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/aws225 |journal=Brain |language=en |volume=135 |issue=9 |pages=2585–2612 |doi=10.1093/brain/aws225 |issn=0006-8950 |pmc=3437034 |pmid=22961543}}</ref>

===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 [[Ligand (biochemistry)|ligands]] to the channel.<ref>Ravna, A.W., Sylte, I. (2011). Homology Modeling of Transporter Proteins (Carriers and Ion Channels). In: Orry, A., Abagyan, R. (eds) Homology Modeling. Methods in Molecular Biology, vol 857. Humana Press. https://doi.org/10.1007/978-1-61779-588-6_12</ref>

====Voltage-gated====

{{Main|Voltage-gated ion channel}}
Voltage-gated ion channels open and close in response to [[membrane potential]].
* [[Voltage-gated sodium channel]]s: This family contains at least 9 members and is largely responsible for [[action potential]] creation and propagation. The pore-forming α subunits are very large (up to 4,000 [[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 [[glycosylation|glycosylated]].
* [[Voltage-gated calcium channel]]s: This family contains 10 members, though these are known to coassemble with α<sub>2</sub>δ, 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 [[Transient response potential channel|TRP channels]].
* [[Voltage-gated potassium channel]]s (K<sub>V</sub>): 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]]s.  The α subunits have six transmembrane segments, homologous to a single domain of the sodium channels.  Correspondingly, they assemble as [[tetramer protein|tetramer]]s to produce a functioning channel.
* Some [[transient receptor potential channel]]s: This group of channels, normally referred to simply as TRP channels, is named after their role in [[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-gated ion channel|voltage]], intracellular [[Calcium in biology|Ca<sup>2+</sup>]], pH, redox state, osmolarity, and [[Stretch-activated ion channel|mechanical stretch]]. These channels also vary according to the ion(s) they pass, some being selective for Ca<sup>2+</sup> while others are less selective, acting as cation channels. This family is subdivided into 6 subfamilies based on homology: classical ([[TRPC]]), vanilloid receptors ([[TRPV]]), melastatin ([[TRPM]]), polycystins ([[TRPP]]), mucolipins ([[TRPML]]), and ankyrin transmembrane protein 1 ([[TRPA (channel)|TRPA]]).
* Hyperpolarization-activated [[cyclic nucleotide-gated channel]]s: The opening of these channels is due to [[Hyperpolarization (biology)|hyperpolarization]] rather than the depolarization required for other cyclic nucleotide-gated channels. These channels are also sensitive to the cyclic nucleotides [[Cyclic adenosine monophosphate|cAMP]] and [[Cyclic guanosine monophosphate|cGMP]], which alter the voltage sensitivity of the channel's opening. These channels are permeable to the monovalent cations K<sup>+</sup> and Na<sup>+</sup>. 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 [[Cardiac pacemaker|pacemaking]] channels in the heart, particularly the [[SA node]].
* [[Voltage-gated proton channel]]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]], [[neutrophils]], [[macrophages]]) during the "respiratory burst."  When bacteria or other microbes are engulfed by phagocytes, the enzyme [[NADPH oxidase]] assembles in the membrane and begins to produce [[reactive oxygen species]] (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) ====
{{Main|Ligand-gated ion channel}}

Also known as ionotropic [[receptor (biochemistry)|receptors]], this group of channels open in response to specific ligand molecules binding to the extracellular domain of the receptor protein.<ref name="Openstax Anatomy & Physiology attribution"> {{cite book|last1=Betts|first1=J Gordon|last2=Desaix|first2=Peter|last3=Johnson|first3=Eddie|last4=Johnson|first4=Jody E|last5=Korol|first5=Oksana|last6=Kruse|first6=Dean|last7=Poe|first7=Brandon|last8=Wise|first8=James|last9=Womble|first9=Mark D|last10=Young|first10=Kelly A|title=Anatomy & Physiology|location=Houston|publisher=OpenStax CNX|isbn=978-1-947172-04-3|date=July 6, 2023|at=12.4 The Action Potential}}</ref> 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 [[Acetylcholine receptor|nicotinic acetylcholine receptors]], [[Glutamate receptors|ionotropic glutamate-gated receptors]], [[acid-sensing ion channel]]s (ASICs),<ref>{{cite journal | vauthors = Hanukoglu I | title = ASIC and ENaC type sodium channels: conformational states and the structures of the ion selectivity filters | journal = The FEBS Journal | volume = 284 | issue = 4 | pages = 525–545 | date = February 2017 | pmid = 27580245 | doi = 10.1111/febs.13840 | s2cid = 24402104 | url = https://zenodo.org/record/890906 }}</ref> [[P2X Receptors|ATP-gated P2X receptors]], and the anion-permeable γ-aminobutyric acid-gated [[GABA receptor|GABA<sub>A</sub> receptor]].

Ion channels activated by second messengers may also be categorized in this group, although [[Ligand (biochemistry)|ligands]] and second messengers are otherwise distinguished from each other.{{cn|date=August 2024}}

==== Lipid-gated ====
{{Main|Lipid-gated ion channels}}

This group of channels opens in response to specific [[lipid]] molecules binding to the channel's transmembrane domain typically near the inner leaflet of the plasma membrane.<ref>{{cite journal | vauthors = Hansen SB | title = Lipid agonism: The PIP2 paradigm of ligand-gated ion channels | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1851 | issue = 5 | pages = 620–8 | date = May 2015 | pmid = 25633344 | pmc = 4540326 | doi = 10.1016/j.bbalip.2015.01.011 }}</ref> Phosphatidylinositol 4,5-bisphosphate ([[Phosphatidylinositol 4,5-bisphosphate|PIP<sub>2</sub>]]) and phosphatidic acid ([[Phosphatidic acid|PA]]) are the best-characterized lipids to gate these channels.<ref>{{cite journal | vauthors = Hansen SB, Tao X, MacKinnon R | title = Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2 | journal = Nature | volume = 477 | issue = 7365 | pages = 495–8 | date = August 2011 | pmid = 21874019 | pmc = 3324908 | doi = 10.1038/nature10370 | bibcode = 2011Natur.477..495H }}</ref><ref>{{cite journal | vauthors = Gao Y, Cao E, Julius D, Cheng Y | title = TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action | journal = Nature | volume = 534 | issue = 7607 | pages = 347–51 | date = June 2016 | pmid = 27281200 | pmc = 4911334 | doi = 10.1038/nature17964 | bibcode = 2016Natur.534..347G }}</ref><ref>{{cite journal | vauthors = Cabanos C, Wang M, Han X, Hansen SB | title = 2 Antagonism of TREK-1 Channels | journal = Cell Reports | volume = 20 | issue = 6 | pages = 1287–1294 | date = August 2017 | pmid = 28793254 | pmc = 5586213 | doi = 10.1016/j.celrep.2017.07.034 }}</ref> Many of the leak potassium channels are gated by lipids including the [[Inward-rectifier potassium ion channel|inward-rectifier potassium channels]] and two pore domain potassium channels TREK-1 and TRAAK. [[KCNQ channels|KCNQ potassium channel family]] are gated by PIP<sub>2</sub>.<ref>{{cite journal | vauthors = Brown DA, Passmore GM | title = Neural KCNQ (Kv7) channels | journal = British Journal of Pharmacology | volume = 156 | issue = 8 | pages = 1185–95 | date = April 2009 | pmid = 19298256 | pmc = 2697739 | doi = 10.1111/j.1476-5381.2009.00111.x }}</ref> The voltage activated potassium channel (Kv) is regulated by PA. Its midpoint of activation shifts +50 mV upon PA hydrolysis, near resting membrane potentials.<ref>{{cite journal | vauthors = Hite RK, Butterwick JA, MacKinnon R | title = Phosphatidic acid modulation of Kv channel voltage sensor function | journal = eLife | volume = 3 | date = October 2014 | pmid = 25285449 | pmc = 4212207 | doi = 10.7554/eLife.04366 | doi-access = free }}</ref> 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]]s from the inside of the [[cell membrane]] – rather than from outside the cell, as in the case for ligands.
* Some potassium channels:
** [[Inward-rectifier potassium ion channel|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 [[Adenosine triphosphate|ATP]], PIP<sub>2</sub>, and [[G-protein]] βγ subunits. They are involved in important physiological processes such as pacemaker activity in the heart, insulin release, and potassium uptake in [[glia|glial cells]]. They contain only two transmembrane segments, corresponding to the core pore-forming segments of the K<sub>V</sub> and K<sub>Ca</sub> channels. Their α subunits form tetramers.
** [[Calcium-activated potassium channel]]s: This family of channels is activated by intracellular Ca<sup>2+</sup> and contains 8 members.
** [[Tandem pore domain potassium channel]]: This family of 15 members form what are known as [[leak channel]]s, and they display [[GHK current equation|Goldman-Hodgkin-Katz]] (open) [[rectifier|rectification]]. Contrary to their common name of 'Two-pore-domain potassium channels', these channels have only one pore but two pore domains per subunit.<ref>{{cite web|url=http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=79|title=Two P domain potassium channels|publisher=[[Guide to Pharmacology]]|access-date=2019-05-28}}</ref><ref name="Rang60">{{cite book|title=Pharmacology|url=https://archive.org/details/clinicalpharmaco00frcp|url-access=limited| vauthors = Rang HP |publisher=Churchill Livingstone|year=2003|isbn=978-0-443-07145-4|edition=8th|location=Edinburgh|page=[https://archive.org/details/clinicalpharmaco00frcp/page/n74 59]}}</ref>
* [[Two-pore channel]]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.<ref>{{cite journal | vauthors = Kintzer AF, Stroud RM | title = Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana | journal = Nature | volume = 531 | issue = 7593 | pages = 258–62 | date = March 2016 | pmid = 26961658 | pmc = 4863712 | doi = 10.1038/nature17194 | quote = Other than Ca2+ and Na+ channels that are formed by four intramolecular repeats, together forming the tetrameric channel's pore, the new channel had just two Shaker-like repeats, each of which was equipped with one pore domain. Because of this unusual topology, this channel, present in animals as well as plants, was named Two Pore Channel1 (TPC1). | bibcode = 2016Natur.531..258K | biorxiv = 10.1101/041400 }}</ref><ref>{{cite journal | vauthors = Spalding EP, Harper JF | title = The ins and outs of cellular Ca(2+) transport | journal = Current Opinion in Plant Biology | volume = 14 | issue = 6 | pages = 715–20 | date = December 2011 | pmid = 21865080 | pmc = 3230696 | doi = 10.1016/j.pbi.2011.08.001 | quote = The best candidate for a vacuolar Ca2+ release channel is TPC1, a homolog of a mammalian voltage-gated Ca2+ channel that possesses two pores and twelve membrane spans. }}</ref><ref>{{cite journal | vauthors = Brown BM, Nguyen HM, Wulff H | title = Recent advances in our understanding of the structure and function of more unusual cation channels | journal = F1000Research | volume = 8 | pages = 123 | date = 2019-01-30 | pmid = 30755796 | pmc = 6354322 | doi = 10.12688/f1000research.17163.1 | quote = Organellar two-pore channels (TPCs) are an interesting type of channel that, as the name suggests, has two pores. | doi-access = free }}</ref><ref>{{cite journal | vauthors = Jammes F, Hu HC, Villiers F, Bouten R, Kwak JM | title = Calcium-permeable channels in plant cells | journal = The FEBS Journal | volume = 278 | issue = 22 | pages = 4262–76 | date = November 2011 | pmid = 21955583 | doi = 10.1111/j.1742-4658.2011.08369.x | s2cid = 205884593 | quote = The Arabidopsis two‐pore channel (AtTPC1) has been predicted to have 12 transmembrane helices and two pores (red lines). | doi-access = free }}</ref><ref>{{cite thesis|url=http://discovery.ucl.ac.uk/1335830/1/1335830.pdf|quote=It is believed that TPCs, with their two pores, dimerise to form a functional channel.|title=Molecular characterisation of NAADP-gated two-pore channels| first = Robert | last = Hooper | name-list-style = vanc |date=September 2011}}</ref>
* [[Light-gated ion channels|Light-gated channels]] like [[channelrhodopsin]] are directly opened by [[photon]]s.
* [[Mechanosensitive ion channel]]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 [[Cyclic adenosine monophosphate|cAMP]] or [[Cyclic guanosine monophosphate|cGMP]]. These channels are primarily permeable to monovalent cations such as K<sup>+</sup> and Na<sup>+</sup>. They are also permeable to Ca<sup>2+</sup>, 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 [[Trp channel|transient receptor potential ion channel]] superfamily, such as [[TRPV1]] or [[TRPM8]], are opened either by hot or cold temperatures.

===Classification by type of ions===
* [[Chloride channel]]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]] is the most abundant anion, and hence they are known as chloride channels.
* [[Potassium channel]]s
** [[Voltage-gated potassium channel]]s e.g., Kvs, Kirs etc.
** [[Calcium-activated potassium channel]]s e.g., BKCa or MaxiK, SK, etc.
** [[Inward-rectifier potassium ion channel|Inward-rectifier potassium channels]]
** [[Two P potassium channel|Two-pore-domain potassium channels]]: This family of 15 members form what is known as [[leak channel]]s, and they display [[GHK current equation|Goldman-Hodgkin-Katz]] (open) [[rectifier|rectification]].
* [[Sodium channels]]
** [[Voltage-gated sodium channel]]s (NaVs)
** [[Epithelial sodium channel]]s (ENaCs)<ref name="2016-Hanukoglu" >{{cite journal | vauthors = Hanukoglu I, Hanukoglu A | title = Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases | journal = Gene | volume = 579 | issue = 2 | pages = 95–132 | date = April 2016 | pmid = 26772908 | pmc = 4756657 | doi = 10.1016/j.gene.2015.12.061 }}</ref>
* [[Calcium channel]]s (CaVs)
* Phosphate channels: To date, only one phosphate channel, [[Xenotropic and polytropic retrovirus receptor 1]] (XPR1), has been identified in animals. It is a pyrophosphate-gated channel.<ref>{{Cite journal |last1=Lu |first1=Yi |last2=Yue |first2=Chen-Xi |last3=Zhang |first3=Li |last4=Yao |first4=Deqiang |last5=Xia |first5=Ying |last6=Zhang |first6=Qing |last7=Zhang |first7=Xinchen |last8=Li |first8=Shaobai |last9=Shen |first9=Yafeng |last10=Cao |first10=Mi |last11=Guo |first11=Chang-Run |last12=Qin |first12=An |last13=Zhao |first13=Jie |last14=Zhou |first14=Lu |last15=Yu |first15=Ye |date=2024-09-26 |title=Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1 |url=https://www.science.org/doi/10.1126/science.adp3252 |journal=Science |volume=386 |issue=6723 |pages=eadp3252 |language=en |doi=10.1126/science.adp3252 |pmid=39325866 |bibcode=2024Sci...386P3252L |issn=0036-8075}}</ref>
* Proton channels
** [[Voltage-gated proton channels]]
* ''Non-selective cation channels'': These non-selectively allow many types of cations, mainly Na<sup>+</sup>, K<sup>+</sup> and Ca<sup>2+</sup>, through the channel.
** Most [[transient receptor potential|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]], [[Golgi apparatus]], and [[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, Orai) and Chloride channels (ClC)
* Intracellular channels, which are further classified into different organelles
** [[Endoplasmic reticulum]] channels: RyR, IP3R
** 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]]s: This group of channels, normally referred to simply as TRP channels, is named after their role in ''[[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-gated ion channel|voltage]], intracellular Ca<sup>2+</sup>, [[pH]], [[redox]] state, [[osmolarity]], and [[Stretch-activated ion channel|mechanical stretch]]. These channels also vary according to the ion(s) they pass, some being selective for Ca<sup>2+</sup> while others are less selective cation channels. This family is subdivided into 6 subfamilies based on homology: canonical TRP ([[TRPC]]), vanilloid receptors ([[TRPV]]), melastatin ([[TRPM]]), polycystins ([[TRPP]]), mucolipins ([[TRPML]]), and ankyrin transmembrane protein 1 ([[TRPA (channel)|TRPA]]).

== Detailed structure ==

Channels differ with respect to the ion they let pass (for example, [[sodium ion|Na<sup>+</sup>]], [[potassium ion|K<sup>+</sup>]], [[chloride ion|Cl<sup>−</sup>]]), the ways in which they may be regulated, the number of subunits of which they are composed and other aspects of structure.<ref>{{cite book | vauthors = Lim C, Dudev T | title = The Alkali Metal Ions: Their Role for Life | chapter = Potassium Versus Sodium Selectivity in Monovalent Ion Channel Selectivity Filters | volume = 16 | pages = 325–47 | date = 2016 | pmid = 26860306 | doi = 10.1007/978-3-319-21756-7_10 | publisher = Springer | veditors = Sigel A, Sigel H, Sigel R | series = Metal Ions in Life Sciences | isbn = 978-3-319-21755-0 }}</ref> Channels belonging to the largest class, which includes the voltage-gated channels that underlie the nerve impulse, consist of four or sometimes five <ref>doi: https://doi.org/10.1038/d41586-023-02486-9</ref> subunits with six [[transmembrane helix|transmembrane helices]] 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.{{cn|date=August 2024}}

The existence and mechanism for ion selectivity was first postulated in the late 1960s by [[Bertil Hille]] and [[Clay Armstrong]].<ref name="pmid5315827">{{cite journal | vauthors = Hille B | title = The permeability of the sodium channel to organic cations in myelinated nerve | journal = The Journal of General Physiology | volume = 58 | issue = 6 | pages = 599–619 | date = December 1971 | pmid = 5315827 | pmc = 2226049 | doi = 10.1085/jgp.58.6.599 | author-link1 = Bertil Hille }}</ref><ref name="pmid4644327">{{cite journal | vauthors = Bezanilla F, Armstrong CM | title = Negative conductance caused by entry of sodium and cesium ions into the potassium channels of squid axons | journal = The Journal of General Physiology | volume = 60 | issue = 5 | pages = 588–608 | date = November 1972 | pmid = 4644327 | pmc = 2226091 | doi = 10.1085/jgp.60.5.588 }}</ref><ref name="pmid4541077">{{cite journal | vauthors = Hille B | title = Potassium channels in myelinated nerve. Selective permeability to small cations | journal = The Journal of General Physiology | volume = 61 | issue = 6 | pages = 669–86 | date = June 1973 | pmid = 4541077 | pmc = 2203488 | doi = 10.1085/jgp.61.6.669 | author-link1 = Bertil Hille }}</ref><ref name="pmid    1194886">{{cite journal | vauthors = Hille B | title = Ionic selectivity, saturation, and block in sodium channels. A four-barrier model | journal = The Journal of General Physiology | volume = 66 | issue = 5 | pages = 535–60 | date = November 1975 | pmid = 1194886 | pmc = 2226224 | doi = 10.1085/jgp.66.5.535 | author-link1 = Bertil Hille }}</ref><ref name="pmid29363566">{{cite journal | vauthors = Hille B | title = Journal of General Physiology: Membrane permeation and ion selectivity | journal = The Journal of General Physiology | volume = 150 | issue = 3 | pages = 389–400 | date = March 2018 | pmid = 29363566 | pmc = 5839722 | doi = 10.1085/jgp.201711937 | author-link1 = Bertil Hille }}</ref> 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]] using [[crystallography|X-ray crystallography]] won a share of the 2003 [[Nobel Prize in Chemistry]].<ref name="pmid9525859">{{cite journal | vauthors = Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R | display-authors = 6 | title = The structure of the potassium channel: molecular basis of K+ conduction and selectivity | journal = Science | volume = 280 | issue = 5360 | pages = 69–77 | date = April 1998 | pmid = 9525859 | doi = 10.1126/science.280.5360.69 | bibcode = 1998Sci...280...69D }}</ref>

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.<ref name="pmid12721618">{{cite journal | vauthors = Jiang Y, Lee A, Chen J, Ruta V, Cadene M, Chait BT, MacKinnon R | title = X-ray structure of a voltage-dependent K+ channel | journal = Nature | volume = 423 | issue = 6935 | pages = 33–41 | date = May 2003 | pmid = 12721618 | doi = 10.1038/nature01580 | bibcode = 2003Natur.423...33J | s2cid = 4347957 | doi-access =  }}</ref><ref name="pmid16598263">{{cite journal | vauthors = Lunin VV, Dobrovetsky E, Khutoreskaya G, Zhang R, Joachimiak A, Doyle DA, Bochkarev A, Maguire ME, Edwards AM, Koth CM | display-authors = 6 | title = Crystal structure of the CorA Mg2+ transporter | journal = Nature | volume = 440 | issue = 7085 | pages = 833–7 | date = April 2006 | pmid = 16598263 | pmc = 3836678 | doi = 10.1038/nature04642 | bibcode = 2006Natur.440..833L }}</ref> 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]], [[biochemistry]], [[gene]] sequence comparison and [[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==
{{main|Channel modulator}}
Chemical substances can modulate the activity of ion channels, for example by blocking or activating them.

===Ion channel blockers===
{{main|Ion channel blocker}}
A variety of [[ion channel blocker]]s (inorganic and organic molecules) can modulate ion channel activity and conductance.
Some commonly used blockers include:
* [[Tetrodotoxin]] (TTX), used by [[puffer fish]] and some types of [[newts]] for defense.  It blocks sodium channels.
* [[Saxitoxin]] is produced by a [[dinoflagellate]] also known as "[[red tide]]".  It blocks voltage-dependent sodium channels.
* [[Conotoxin]] is used by [[cone snails]] to hunt prey.
* [[Lidocaine]] and [[novocaine]] belong to a class of [[local anesthetics]] which block sodium ion channels.
* [[Dendrotoxin]] is produced by [[mamba]] [[snakes]], and blocks potassium channels.
* [[Iberiotoxin]] is produced by the ''[[Hottentotta tamulus]]'' (Eastern Indian scorpion) and blocks potassium channels.
* [[Heteropodatoxin]] is produced by ''[[Heteropoda venatoria]]'' (brown huntsman spider or laya) and blocks potassium channels.

===Ion channel activators===
{{main|Ion channel opener}}
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]]s, such as [[Bay K8644]]
* [[Chloride channel opener]]s, such as [[phenanthroline]]
* [[Potassium channel opener]]s, such as [[minoxidil]]
* [[Sodium channel opener]]s, such as [[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 [[Channelopathy|channelopathies]]. See [[:Category:Channelopathies]] for a full list.
* [[Shaker gene]] 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]] (PC) and [[potassium aggravated myotonias|potassium-aggravated myotonias]] (PAM)
* [[Generalized epilepsy with febrile seizures plus]] (GEFS+)
* [[Episodic ataxia]] (EA), characterized by sporadic bouts of severe discoordination with or without [[myokymia]], and can be provoked by stress, startle, or heavy exertion such as exercise.
* [[Familial hemiplegic migraine]] (FHM)
* [[Spinocerebellar ataxia type 13]]
* [[Long QT syndrome]] is a [[Ventricle (heart)|ventricular]] [[Heart arrhythmia|arrhythmia]] [[syndrome]] caused by [[mutation]]s in one or more of presently ten different [[gene]]s, most of which are [[potassium channel]]s and all of which affect cardiac [[repolarization]].
* [[Brugada syndrome]] is another ventricular arrhythmia caused by [[voltage-gated sodium channel]] gene mutations.
* [[Polymicrogyria]] is a developmental brain malformation caused by [[voltage-gated sodium channel]] and [[NMDA receptor]] gene mutations.<ref>{{cite journal | vauthors = Smith RS, Walsh CA | title = Ion Channel Functions in Early Brain Development | journal = Trends in Neurosciences | volume = 43 | issue = 2 | pages = 103–114 | date = February 2020 | pmid = 31959360 | doi = 10.1016/j.tins.2019.12.004 | pmc = 7092371 }}</ref>
* [[Cystic fibrosis]] is caused by mutations in the CFTR gene, which is a chloride channel.
* [[Mucolipidosis type IV]] 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]], 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.<ref>{{cite journal | vauthors = Molenaar RJ | title = Ion channels in glioblastoma | journal = ISRN Neurology | volume = 2011 | pages = 590249 | year = 2011 | pmid = 22389824 | pmc = 3263536 | doi = 10.5402/2011/590249 | doi-access = free }}</ref>

== History ==
The fundamental properties of currents mediated by ion channels were analyzed by the British [[biophysics|biophysicist]]s [[Alan Hodgkin]] and [[Andrew Huxley]] as part of their [[Nobel Prize in Physiology or Medicine|Nobel Prize]]-winning research on the [[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.<ref>
{{cite journal | vauthors = Pethig R, Kell DB | title = The passive electrical properties of biological systems: their significance in physiology, biophysics and biotechnology | journal = Physics in Medicine and Biology | volume = 32 | issue = 8 | pages = 933–70 | date = August 1987 | pmid = 3306721 | doi = 10.1088/0031-9155/32/8/001 | url = http://dbkgroup.org/Papers/pethig_kell_pmb87.pdf | quote = An expansive review of bioelectrical characteristics from 1987. ... the observation of an inductance (negative capacitance) by Cole and Baker (1941) during measurements of the AC electrical properties of squid axons led directly to the concept of voltage-gated membrane pores, as embodied in the celebrated Hodgkin-Huxley (1952) treatment (Cole 1972, Jack er a1 1975), as the crucial mechanism of neurotransmission. | bibcode = 1987PMB....32..933P | s2cid = 250880496 }}
</ref><ref>
{{cite journal | vauthors = Cole KS, Baker RF | title = Longitudinal Impedance of the Squid Giant Axon | journal = The Journal of General Physiology | volume = 24 | issue = 6 | pages = 771–88 | date = July 1941 | pmid = 19873252 | pmc = 2238007 | doi = 10.1085/jgp.24.6.771 | publisher = The Rockefeller University Press | quote = Describes what happens when you stick a [[squid giant axon|giant squid axon]] with electrodes and pass through an alternating current, and then notice that sometimes the voltage rises with time, and sometimes it decreases. The inductive reactance is a property of the axon and requires that it contain an inductive structure. The variation of the impedance with interpolar distance indicates that the inductance is in the membrane }}
</ref> The existence of ion channels was confirmed in the 1970s by [[Bernard Katz]] and [[Ricardo Miledi]] using noise analysis {{Citation needed|date=March 2022|reason=Which paper(s) are you referring here?}}. It was then shown more directly with an [[electrophysiology|electrical recording technique]] known as the "[[patch clamp]]", which led to a Nobel Prize to [[Erwin Neher]] and [[Bert Sakmann]], 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 [[Electrophysiology#Planar patch clamp|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]] for his studies on the physico-chemical properties of ion channel structure and function, including [[x-ray crystallography|x-ray crystallographic]] [[protein structure|structure]] studies.

== Culture ==
[[Image:Birth of an Idea.jpg|thumb|right|''Birth of an Idea'' (2007) by [[Julian Voss-Andreae]]. The sculpture was commissioned by [[Roderick MacKinnon]] based on the molecule's atomic coordinates that were determined by MacKinnon's group in 2001.]]

[[Roderick MacKinnon]] commissioned ''Birth of an Idea'', a {{convert|5|ft|adj=on}} tall sculpture based on the [[KcsA potassium channel]].<ref>{{cite journal | first = Philip | last = Ball | name-list-style =vanc |date=March 2008 | title = The crucible: Art inspired by science should be more than just a pretty picture | journal = Chemistry World | volume = 5 | pages = 42–43 | url = http://www.rsc.org/chemistryworld/Issues/2008/March/ColumnThecrucible.asp | access-date=2009-01-12 | issue = 3}}</ref> The artwork contains a wire object representing the channel's interior with a blown glass object representing the main cavity of the channel structure.

== Ion channels and stochastic processes ==
The behavior of ion channels can be usefully modeled using mathematics and probability. [[Stochastic process|Stochastic processes]] are mathematical models of systems and phenomena that appear to vary in a random manner.<ref>{{Cite book |last=Doob |first=Joseph L. |title=Stochastic processes |date=1990 |publisher=Wiley |isbn=978-0-471-52369-7 |series=Wiley classics library edition |location=New York, NY}}</ref> A very simple example is flipping a coin; each flip has an equal chance to be heads or tails, the chances are not influenced by the outcome of past flips, and we can say that p<sub>heads</sub> = 0.5 and p<sub>tails</sub> = 0.5.<ref name=":0">{{Cite web |last=Chong |first=Y. D. |title=The Simplest Markov Chain - The Coin-Flipping Game |url=https://phys.libretexts.org/Bookshelves/Mathematical_Physics_and_Pedagogy/Computational_Physics_(Chong)/12%3A_Markov_Chains/12.01%3A_The_Simplest_Markov_Chain-_The_Coin-Flipping_Game#:~:text=At%20each%20step%2C%20we%20flip,sequences%20is%20a%20Markov%20chain. |access-date=2024-11-23 |website=LibreTexts|date=27 April 2021 }}</ref>

A particularly relevant form of stochastic processes in the study of ion channels is [[Markov chain|Markov chains]]. In a Markov chain, there are multiple states, each of which has given chances to transition to different states over a particular period of time.<ref name=":0" /> Ion channels undergo state transitions (e.g. open, closed, inactive) that behave like Markov chains.<ref>{{Cite journal |last1=Lampert |first1=Angelika |last2=Korngreen |first2=Alon |date=2014 |title=Markov modeling of ion channels: implications for understanding disease |url=https://pubmed.ncbi.nlm.nih.gov/24560138 |journal=Progress in Molecular Biology and Translational Science |volume=123 |pages=1–21 |doi=10.1016/B978-0-12-397897-4.00009-7 |issn=1878-0814 |pmid=24560138}}</ref> Markov chain analysis can be used to make conclusions regarding the nature of a given ion channel, including the likely number of open and closed states.<ref>{{Cite journal |last1=Siekmann |first1=Ivo |last2=Larry E Wagner |first2=I. I. |last3=Yule |first3=David |last4=Fox |first4=Colin |last5=Bryant |first5=David |last6=Crampin |first6=Edmund J. |last7=Sneyd |first7=James |date=2011-04-20 |title=MCMC Estimation of Markov Models for Ion Channels |journal=Biophysical Journal |language=en |volume=100 |issue=8 |pages=1919–1929 |doi=10.1016/j.bpj.2011.02.059 |pmc=3077709 |pmid=21504728|bibcode=2011BpJ...100.1919S }}</ref> We can also use Markov chain analysis to produce models that accurately simulate the insertion of ion channels into cell membranes.<ref>{{Cite journal |last1=Sato |first1=Daisuke |last2=Hernández-Hernández |first2=Gonzalo |last3=Matsumoto |first3=Collin |last4=Tajada |first4=Sendoa |last5=Moreno |first5=Claudia M. |last6=Dixon |first6=Rose E. |last7=O’Dwyer |first7=Samantha |last8=Navedo |first8=Manuel F. |last9=Trimmer |first9=James S. |last10=Clancy |first10=Colleen E. |last11=Binder |first11=Marc D. |last12=Santana |first12=L. Fernando |date=2019-08-01 |title=A stochastic model of ion channel cluster formation in the plasma membrane |url=https://rupress.org/jgp/article/151/9/1116/120461/A-stochastic-model-of-ion-channel-cluster |journal=Journal of General Physiology |volume=151 |issue=9 |pages=1116–1134 |doi=10.1085/jgp.201912327 |pmid=31371391 |pmc=6719406 |issn=0022-1295}}</ref>

Markov chains can also be used in combination with the [[stochastic matrix]] to determine the [[stable distribution]] matrix by solving the equation PX=X, where P is the stochastic matrix and X is the stable distribution matrix. This stable distribution matrix tells us the relative frequencies of each state after a long time, which in the context of ion channels can be the frequencies of the open, closed, and inactive states for an ion channel.<ref name=":1">{{Citation |title=Markov Chains |date=2003 |work=Applied Probability and Queues |series=Stochastic Modelling and Applied Probability |volume=51 |pages=3–38 |url=http://link.springer.com/10.1007/0-387-21525-5_1 |access-date=2024-12-07 |place=New York, NY |publisher=Springer New York |language=en |doi=10.1007/0-387-21525-5_1 |isbn=978-0-387-00211-8}}</ref> Note that Markov chain assumptions apply, including that (1) all transition probabilities for each state sum to one, (2) the probability model applies to all possible states, and (3) that the probability of transitions are constant over time. Therefore, Markov chains have limited applicability in some situations. <ref name=":1" />

There are a variety of other stochastic processes that are utilized in the study of ion channels, but are too complex to relate here and can be examined more closely elsewhere.<ref>{{Cite journal |last1=Ball |first1=Frank G. |last2=Rice |first2=John A. |date=1992 |title=Stochastic models for ion channels: Introduction and bibliography |url=https://linkinghub.elsevier.com/retrieve/pii/002555649290023P |journal=Mathematical Biosciences |language=en |volume=112 |issue=2 |pages=189–206 |doi=10.1016/0025-5564(92)90023-P|pmid=1283350 }}</ref>

== See also ==
* [[Alpha helix]]
* [[Babycurus toxin 1]]
* [[Ion channel family]] as defined in [[Pfam]] and [[InterPro]]
* [[Ki Database|K<sub>i</sub> Database]]
* [[Lipid bilayer#Ion pumps and channels|Lipid bilayer ion channels]]
* [[Magnesium transport]]
* [[Neurotoxin]]
* [[Passive transport]]
* [[Synthetic ion channels]]
* [[Transmembrane receptor]]
{{clear}}

== References ==
{{Reflist|33em}}

== External links ==
{{wikiversity|Poisson–Boltzmann profile for an ion channel}}
* {{cite web | url = http://www.theweisslab.com/ | title = The Weiss Lab | access-date =  | date =  | work = The Weiss Lab is investigating the molecular and cellular mechanisms underlying human diseases caused by dysfunction of ion channels | pages =  | archive-url = https://web.archive.org/web/20240225183204/https://www.theweisslab.com/ | archive-date = 2024-02-25 | quote =  | url-status = dead }}
* {{cite web | url = http://www.guidetopharmacology.org/GRAC/ReceptorFamiliesForward?type=IC| title = Voltage-Gated Ion Channels | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology }}
* {{cite web | url = http://www.trpchannel.org | title = TRIP Database | work = a manually curated database of protein-protein interactions for mammalian TRP channels}}
* {{MeSH name|Ion Channels}}

{{Ion channels}}
{{Ligand-gated ion channels}}
{{channel blockers}}

{{Authority control}}

[[Category:Cell communication]]
[[Category:Electrophysiology]]
[[Category:Integral membrane proteins]]
[[Category:Ion channels| ]]
[[Category:Neurochemistry]]
[[Category:Protein families]]