Editing Ion channel (section)

== 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.