View source for Voltage-gated potassium channel



'''Voltage-gated potassium channels''' are [[potassium channel|transmembrane channels specific for potassium]] and [[Voltage-gated ion channel|sensitive to voltage changes]] in the cell's [[membrane potential]]. They play a crucial role during [[action potentials]] in returning the depolarized cell to a resting state.

==Classification==

===Alpha subunits===
Alpha subunits form the actual conductance pore.  Based on sequence homology of the hydrophobic transmembrane cores, the alpha subunits of voltage-gated potassium channels have been grouped into 12 classes labeled K<sub>v</sub>1-12.<ref name="Gutman">{{cite journal |author=Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stuhmer W, Wang X|title=International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels.|journal= Pharmacol Rev |volume= 57 |issue= 4 |pages= 473-508 |year= 2005 |pmid= 16382104 | doi = 10.1124/pr.57.4.10}}</ref>  The following is a list of the 40 known human voltage-gated potassium channel alpha subunits grouped first according to function and then subgrouped according to the K<sub>v</sub> sequence homology classification scheme:

====Delayed rectifier====
non-inactivating
*K<sub>v</sub>α1.x - [[shaker superfamily of potassium channels|Shaker-related]]: K<sub>v</sub>1.1 ({{Gene|KCNA1}}), K<sub>v</sub>1.2 ({{Gene|KCNA2}}), K<sub>v</sub>1.3 ({{Gene|KCNA3}}), K<sub>v</sub>1.4 ({{Gene|KCNA4}}), K<sub>v</sub>1.5 ({{Gene|KCNA5}}), K<sub>v</sub>1.6 ({{Gene|KCNA6}}), K<sub>v</sub>1.7 ({{Gene|KCNA7}}), K<sub>v</sub>1.8 ({{Gene|KCNA10}})
*K<sub>v</sub>α2.x - Shab-related: K<sub>v</sub>2.1 ({{Gene|KCNB1}}), K<sub>v</sub>2.2 ({{Gene|KCNB2}})
*K<sub>v</sub>α3.x - Shaw-related: K<sub>v</sub>3.1 ({{Gene|KCNC1}}), K<sub>v</sub>3.2 ({{Gene|KCNC2}})
*K<sub>v</sub>α7.x: K<sub>v</sub>7.1 ({{Gene|KCNQ1}}) - [[KvLQT1]], K<sub>v</sub>7.2 ({{Gene|KCNQ2}}), K<sub>v</sub>7.3 ({{Gene|KCNQ3}}), K<sub>v</sub>7.4 ({{Gene|KCNQ4}}), K<sub>v</sub>7.5 ({{Gene|KCNQ5}}) 
*K<sub>v</sub>α10.x: K<sub>v</sub>10.1 ({{Gene|KCNH1}})

====A-type potassium channel====
rapidly inactivating
*K<sub>v</sub>α3.x - Shaw-related: K<sub>v</sub>3.3 ({{Gene|KCNC3}}), K<sub>v</sub>3.4 ({{Gene|KCNC4}})
*K<sub>v</sub>α4.x - Shal-related: K<sub>v</sub>4.1 ({{Gene|KCND1}}), K<sub>v</sub>4.2 ({{Gene|KCND2}}), K<sub>v</sub>4.3 ({{Gene|KCND3}})

====Outward-rectifying====
*K<sub>v</sub>α10.x: K<sub>v</sub>10.2 ({{Gene|KCNH2}})

====Inward-rectifying====
*K<sub>v</sub>α11.x - [[ether-a-go-go potassium channels]]: K<sub>v</sub>11.1 ({{Gene|KCNH2}}) - [[hERG]], K<sub>v</sub>11.2 ({{Gene|KCNH6}}), K<sub>v</sub>11.3 ({{Gene|KCNH7}})

====Slowly activating====
*K<sub>v</sub>α12.x: K<sub>v</sub>12.1 ({{Gene|KCNH8}}), K<sub>v</sub>12.2 ({{Gene|KCNH3}}), K<sub>v</sub>12.3 ({{Gene|KCNH4}})

====Modifier/silencer====
Unable to form functional channels as homotetramers but instead heterotetramerize with K<sub>v</sub>α2 family members to form conductive channels.
*K<sub>v</sub>α5.x: K<sub>v</sub>5.1 ({{Gene|KCNF1}})
*K<sub>v</sub>α6.x: K<sub>v</sub>6.1 ({{Gene|KCNG1}}), K<sub>v</sub>6.2 ({{Gene|KCNG2}}), K<sub>v</sub>6.3 ({{Gene|KCNG3}}), K<sub>v</sub>6.4 ({{Gene|KCNG4}})
*K<sub>v</sub>α8.x: K<sub>v</sub>8.1 ({{Gene|KCNV1}}), K<sub>v</sub>8.2 ({{Gene|KCNV2}})
*K<sub>v</sub>α9.x: K<sub>v</sub>9.1 ({{Gene|KCNS1}}), K<sub>v</sub>9.2 ({{Gene|KCNS2}}), K<sub>v</sub>9.3 ({{Gene|KCNS3}})

===Beta subunits===
Beta subunits are auxiliary proteins which associate with alpha subunits in a α<sub>4</sub>β<sub>4</sub> [[stoichiometry]].<ref name="Pongs">{{cite journal |author=Pongs O, Leicher T, Berger M, Roeper J, Bahring R, Wray D, Giese KP, Silva AJ, Storm JF|title=Functional and molecular aspects of voltage-gated K+ channel beta subunits|journal= Ann N Y Acad Sci |volume= 868 |issue= Apr 30 |pages= 344-55 |year= 1999 |pmid= 10414304}}</ref> These subunits do not conduct current on their own but rather modulate the activity of K<sub>v</sub> channels.<ref name="Li">{{cite journal |author=Li Y, Um SY, McDonald TV |title=Voltage-gated potassium channels: regulation by accessory subunits|journal= Neuroscientist |volume= 12 |issue= 3 |pages= 199-210 |year= 2006 |pmid= 16684966}}</ref>
*K<sub>v</sub>β1 ({{Gene|KCNAB1}})
*K<sub>v</sub>β2 ({{Gene|KCNAB2}})
*K<sub>v</sub>β3 ({{Gene|KCNAB3}})
*minK<ref name="Zhang">{{cite journal |author=Zhang M, Jiang M, Tseng GN |title=minK-related peptide 1 associates with Kv4.2 and modulates its gating function: potential role as beta subunit of cardiac transient outward channel?|journal= Circ Res |volume= 88 |issue= 10 |pages= 1012-9 |year= 2001|doi=10.1161/hh1001.090839 |pmid= 11375270}}</ref> ({{Gene|KCNE1}})
*[[MiRP1]]<ref name="McCrossan">{{cite journal |author=McCrossan ZA, Abbott GW |title=The MinK-related peptides|journal= Neuropharmacology |volume= 47 |issue= 6 |pages= 787-821 |year= 2004 |doi=10.1016/j.neuropharm.2004.06.018 |pmid= 15527815}}</ref> ({{Gene|KCNE2}})
*MiRP2 ({{Gene|KCNE3}})
*MiRP3 ({{Gene|KCNE4}})
*KCNE1-like ({{Gene|KCNE1L}})

Proteins minK and MiRP1 are putative hERG beta subunits.<ref name="Anantharam">{{cite journal |author=Anantharam A, Abbott GW |title=Does hERG coassemble with a beta subunit? Evidence for roles of MinK and MiRP1|journal= Novartis Found Symp |volume= 266 |issue= 42 |pages= 112-7, 155-8 |year= 2005|doi=10.1002/047002142X.fmatter |pmid= 16050264}}</ref>

==Animal research==
The voltage-gated K<sup>+</sup> channels that provide the outward currents of [[action potential]]s have similarities to bacterial K<sup>+</sup> channels. 

These channels have been studied by [[X-ray diffraction]], allowing determination of structural features at atomic resolution. 

The function of these channels is explored by [[Electrophysiology|electrophysiological]] studies. 

Genetic approaches include screening for behavioral changes in animals with mutations in K<sup>+</sup> channel genes. Such genetic methods allowed the genetic identification of the "Shaker" K<sup>+</sup> channel gene in ''[[Drosophila]]'' before ion channel gene sequences were well known. 

Study of the altered properties of voltage-gated K<sup>+</sup> channel proteins produced by mutated genes has helped reveal the functional roles of  K<sup>+</sup> channel protein domains and even individual amino acids within their structures. 

==Structure==
Voltage-gated K<sup>+</sup> channels of vertebrates typically are tetramers of four identical subunits arranged as a ring, each contributing to the wall of the trans-membrane K<sup>+</sup> pore.  Each subunit is comprised of six membrane spanning [[hydrophobic]] [[Alpha helix|α-helical sequences]].  A high resolution crystallographic structure of the rat K<sub>v</sub>α1.2/β2 channel has recently been solved (Protein Databank Accession Number {{PDB2|2A79}}).<ref name="Long">{{cite journal |author=Long SB, Campbell EB, Mackinnon R|title=Crystal structure of a mammalian voltage-dependent Shaker family K+ channel|journal= Science |volume= 309 |issue= 5736 |pages= 897-903 |year= 2005 |pmid= 16002581 | doi = 10.1126/science.1116269}}</ref>

==Selectivity==
Voltage-gated K<sup>+</sup> channels are selective for K<sup>+</sup> over other [[cation]]s such as Na<sup>+</sup>. There is a selectivity filter at the narrowest part of the transmembrane pore. 

Channel mutation studies revealed the parts of the subunits that are essential for ion selectivity. They include the [[Amino acid#Chemical properties|amino acid]] sequence (Thr-Val-Gly-Tyr-Gly) or (Thr-Val-Gly-Phe-Gly) typical to the selectivity filter of voltage-gated K<sup>+</sup> channels. As K<sup>+</sup> passes through the pore, interactions between potassium ions and water molecules are prevented and the K<sup>+</sup> interacts with specific atomic components of the Thr-Val-Gly-X-Gly sequences from the four channel subunits[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=potassium+channel+AND+stryer%5Bbook%5D+AND+215962%5Buid%5D&rid=stryer.figgrp.1824].

==Open and closed conformations==
Attempts continue to relate the structure of the mammalian voltage-gated K<sup>+</sup> channel to its ability to respond to the voltage that exists across the membrane.<ref>{{cite journal | author = Lee S, Lee A, Chen J, MacKinnon R | title = Structure of the KvAP voltage-dependent K+ channel and its dependence on the lipid membrane. | journal = Proc Natl Acad Sci U S A | volume = 102 | issue = 43 | pages = 15441-6 | year = 2005 | pmid = 16223877}}</ref> Specific domains of the channel subunits have been identified that are important for voltage-sensing and converting between the open conformation of the channel and closed conformations. There are at least two closed conformations; in one, the channel can open if the membrane potential becomes positive inside. Voltage-gated K<sup>+</sup> channels inactivate after opening, entering a distinctive, second closed conformation. In the inactivated conformation, the channel cannot open, even if the transmembrane voltage is favorable. A domain at one end of the K<sup>+</sup> channel protein mediates inactivation. This end of the protein can transiently plug the inner opening of the pore, preventing ion movement through the channel.

==See also==
* [[Ion channel]]

==External links==
* {{MeshName|Voltage-Gated+Potassium+Channels}}
* {{cite journal | author = Li B, Gallin W | title = VKCDB: voltage-gated potassium channel database. | journal = BMC Bioinformatics | volume = 5 | issue = | pages = 3 | year = | id = PMID 14715090}}
* [http://vkcdb.biology.ualberta.ca/ "Voltage-gated potassium channel database (VKCDB)" at ualberta.ca]
* {{UMichOPM|families|superfamily|8}} - Spatial positions of voltage gated potassium channels in membranes

==References==
<references/>

{{Ion channels}}

[[Category:Ion channels]]


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