View source for Potassium channel

You do not have permission to edit this page, for the following reason:

This IP address range has been globally blocked.
This does not affect your ability to read Wikipedia pages.

Most people who see this message have done nothing wrong. Some kinds of blocks restrict editing from specific service providers or telecom companies in response to recent abuse or vandalism, and can sometimes affect other users who are unrelated to that abuse. Review the information below for assistance if you do not believe that you have done anything wrong.

This block affects editing on all Wikimedia wikis.

The IP address or range 62.210.0.0/16 has been globally blocked by ‪Hasley‬ for the following reason(s):

Open proxy/Webhost: See the help page if you are affected:

This block will expire on 16:21, 18 December 2025. Your current IP address is 62.210.136.28.

Even while globally blocked, you will usually still be able to edit pages on Meta-Wiki.

If you believe you were blocked by mistake, you can find additional information and instructions in the No open proxies global policy. Otherwise, to discuss the block please post a request for review on Meta-Wiki. You could also send an email to the stewards VRT queue at stewards@wikimedia.org including all above details.

Other useful links: Global blocks · Help:I have been blocked

You can view and copy the source of this page:

{{Short description|Ion channel that selectively passes K+}}
[[Image:2r9r opm.png|thumb|250px|Potassium channel Kv1.2, structure in a membrane-like environment. Calculated hydrocarbon boundaries of the [[lipid bilayer]] are indicated by red and blue lines.]]
'''Potassium channels''' are the most widely distributed type of [[ion channel]] found in virtually all organisms.<ref name="pmid10798390">{{cite journal | vauthors = Littleton JT, Ganetzky B | title = Ion channels and synaptic organization: analysis of the Drosophila genome | journal = Neuron | volume = 26 | issue = 1 | pages = 35–43 | date = April 2000 | pmid = 10798390 | doi = 10.1016/S0896-6273(00)81135-6 | s2cid = 5694563 | doi-access = free }}</ref> They form [[potassium]]-selective [[ion channel#Basic features|pore]]s that span [[cell membrane]]s. Potassium channels are found in most [[cell (biology)|cell]] types and control a wide variety of cell functions.<ref name="isbn0-87893-321-2">{{cite book | author = Hille, Bertil | title = Ion channels of excitable membranes | publisher = Sinauer | location = Sunderland, Mass | year = 2001 | chapter = Chapter 5: Potassium Channels and Chloride Channels | pages = 131–168 | isbn = 978-0-87893-321-1 }}</ref><ref name="isbn0-8385-7701-6">{{cite book | title = Principles of Neural Science | publisher = McGraw-Hill | location = New York | year = 2000 | edition = 4th | chapter = Chapter 6: Ion Channels | pages = [https://archive.org/details/isbn_9780838577011/page/105 105–124] | isbn = 978-0-8385-7701-1 | vauthors = Jessell TM, Kandel ER, Schwartz JH | first3 = James H. | author-link2 = Eric R. Kandel | title-link = Principles of Neural Science }}</ref>

== Function ==
Potassium channels function to conduct potassium ions down their [[electrochemical gradient]], doing so both rapidly (up to the [[diffusion rate]] of K<sup>+</sup> ions in bulk water) and selectively (excluding, most notably, [[sodium]] despite the [[Ionic radius|sub-angstrom]] difference in ionic radius).<ref>{{cite book | vauthors = Lim C, Dudev T |chapter= Roles and Transport of Sodium and Potassium in Plants|publisher= Springer|date= 2016|series= Metal Ions in Life Sciences|volume=16| journal = The Alkali Metal Ions: Their Role in Life| veditors = Sigel A, Sigel H, Sigel RK | title = The Alkali Metal Ions: Their Role for Life |pages= 325–347|doi=10.1007/978-3-319-21756-7_9|pmid= 26860305 |isbn= 978-3-319-21755-0}}</ref> Biologically, these channels act to set or reset the [[resting potential]] in many cells. In excitable cells, such as [[neuron]]s, the delayed counterflow of potassium ions shapes the [[action potential]].

By contributing to the regulation of the [[cardiac action potential]] duration in [[cardiac muscle]], malfunction of potassium channels may cause life-threatening [[Cardiac arrhythmia|arrhythmias]].  Potassium channels may also be involved in maintaining [[vascular tone]].

They also regulate cellular processes such as the secretion of [[hormones]] (''e.g.'', [[insulin]] release from [[beta cell|beta-cells]] in the [[pancreas]]) so their malfunction can lead to diseases (such as [[Diabetes mellitus type 2|diabetes]]).

Some toxins, such as [[dendrotoxin]], are potent because they block potassium channels.<ref>indirectly cited from reference number 3,4,5,6 in {{cite journal | vauthors = Rehm H, Lazdunski M | title = Purification and subunit structure of a putative K+-channel protein identified by its binding properties for dendrotoxin I | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 13 | pages = 4919–4923 | date = July 1988 | pmid = 2455300 | pmc = 280549 | doi = 10.1073/pnas.85.13.4919 | doi-access = free | bibcode = 1988PNAS...85.4919R }}</ref>

==Types==
There are four major classes of potassium channels:

*[[Calcium-activated potassium channel]] - open in response to the presence of [[calcium]] ions or other signalling molecules.
*[[Inward-rectifier potassium ion channel|Inwardly rectifying potassium channel]] - passes current (positive charge) more easily in the inward direction (into the cell).
*[[Tandem pore domain potassium channel]] - are constitutively open or possess high basal activation, such as the "resting potassium channels" or "leak channels" that set the negative membrane potential of neurons.
*[[Voltage-gated potassium channel]] - are [[voltage-gated ion channel]]s that open or close in response to changes in the [[membrane potential|transmembrane]] [[voltage]].

The following table contains a comparison of the major classes of potassium channels with representative examples (for a complete list of channels within each class, see the respective class pages).

For more examples of pharmacological modulators of potassium channels, see [[potassium channel blocker]] and [[potassium channel opener]].

{| class="wikitable"
|+Potassium channel classes, function, and pharmacology.<ref name="Rang60">{{cite book|title=Pharmacology|author=Rang, HP|publisher=Churchill Livingstone|year=2015|isbn=978-0-443-07145-4|edition=8|location=Edinburgh|page=59}}</ref>
|-
!'''Class'''
! Subclasses
!Function
!Blockers
!Activators
|-
|[[Calcium-activated potassium channel|Calcium-activated]] <br /> 6[[transmembrane helix|T]] & 1[[pore-forming loop|P]]
|
*[[BK channel]]
*[[SK channel]]
*[[IK channel]]
|
* inhibition in response to rising intracellular calcium
|
*[[Charybdotoxin]],<ref name="pmid10777734">{{cite journal | vauthors = Thompson J, Begenisich T | title = Electrostatic interaction between charybdotoxin and a tetrameric mutant of Shaker K(+) channels | journal = Biophysical Journal | volume = 78 | issue = 5 | pages = 2382–2391 | date = May 2000 | pmid = 10777734 | pmc = 1300827 | doi = 10.1016/S0006-3495(00)76782-8 | bibcode = 2000BpJ....78.2382T }}</ref><ref name="pmid8562075">{{cite journal | vauthors = Naranjo D, Miller C | title = A strongly interacting pair of residues on the contact surface of charybdotoxin and a Shaker K+ channel | journal = Neuron | volume = 16 | issue = 1 | pages = 123–130 | date = January 1996 | pmid = 8562075 | doi = 10.1016/S0896-6273(00)80029-X | s2cid = 16794677 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Yu M, Liu SL, Sun PB, Pan H, Tian CL, Zhang LH | title = Peptide toxins and small-molecule blockers of BK channels | journal = Acta Pharmacologica Sinica | volume = 37 | issue = 1 | pages = 56–66 | date = January 2016 | pmid = 26725735 | pmc = 4722972 | doi = 10.1038/aps.2015.139 }}</ref><ref name="Rang60" />
*[[Iberiotoxin]]<ref name="Candia 1992">{{cite journal | vauthors = Candia S, Garcia ML, Latorre R | title = Mode of action of iberiotoxin, a potent blocker of the large conductance Ca(2+)-activated K+ channel | journal = Biophysical Journal | volume = 63 | issue = 2 | pages = 583–590 | date = August 1992 | pmid = 1384740 | pmc = 1262182 | doi = 10.1016/S0006-3495(92)81630-2 | bibcode = 1992BpJ....63..583C }}</ref>
*[[Apamin]]<ref name="Stocker 1999">{{cite journal | vauthors = Stocker M, Krause M, Pedarzani P | title = An apamin-sensitive Ca2+-activated K+ current in hippocampal pyramidal neurons | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 8 | pages = 4662–4667 | date = April 1999 | pmid = 10200319 | pmc = 16389 | doi = 10.1073/pnas.96.8.4662 | doi-access = free | bibcode = 1999PNAS...96.4662S }}</ref><ref name="Rang60" />
*Some types of dendrotoxin from mamba snake venom,<ref name="Rang60" />
*'''[[BK channel|BK<sub>Ca</sub>]]-specific'''
**[[GAL-021]]<ref>{{cite journal | vauthors = McLeod JF, Leempoels JM, Peng SX, Dax SL, Myers LJ, Golder FJ | title = GAL-021, a new intravenous BKCa-channel blocker, is well tolerated and stimulates ventilation in healthy volunteers | journal = British Journal of Anaesthesia | volume = 113 | issue = 5 | pages = 875–883 | date = November 2014 | pmid = 24989775 | doi = 10.1093/bja/aeu182 | doi-access = free }}</ref>
**[[Alcohol (drug)|Ethanol (alcohol)]]<ref name="pmid27238266">{{cite journal | vauthors = Dopico AM, Bukiya AN, Kuntamallappanavar G, Liu J | title = Modulation of BK Channels by Ethanol | journal = International Review of Neurobiology | volume = 128 | pages = 239–279 | year = 2016 | pmid = 27238266 | pmc = 5257281 | doi = 10.1016/bs.irn.2016.03.019 | isbn = 9780128036198 }}</ref>
|{{citation needed|date=May 2019}}

* 1-EBIO
* NS309
* CyPPA
*'''[[BK channel|BK<sub>Ca</sub>]]-specific:''' 
**[[Flufenamic acid]]
**[[Meclofenamic acid]]
**[[Niflumic acid]]
**[[Nimesulide]]
**[[Rottlerin|Rottlerin (mallotoxin)]]
**[[Tolfenamic acid]]
|-
| rowspan="4" |[[Inward-rectifier potassium ion channel|Inwardly rectifying]] <br /> 2[[transmembrane helix|T]] & 1[[pore-forming loop|P]]
|
*[[ROMK]] (K<sub>ir</sub>1.1)
|
* recycling and secretion of potassium in [[nephron]]s
|
*'''Nonselective:'''
**Ba<sup>2+</sup>,<ref name=":0">{{cite book|url=https://archive.org/details/Handbook_of_Inorganic_Chemistry_Patnaik|title=Handbook of inorganic chemicals|publisher=McGraw-Hill|author=Patnaik, Pradyot|date=2003|isbn=978-0-07-049439-8|pages=[https://archive.org/details/Handbook_of_Inorganic_Chemistry_Patnaik/page/n115 77]–78}}</ref>
**Cs<sup>+<ref>{{cite journal | vauthors = Sackin H, Syn S, Palmer LG, Choe H, Walters DE | title = Regulation of ROMK by extracellular cations | journal = Biophysical Journal | volume = 80 | issue = 2 | pages = 683–697 | date = February 2001 | pmid = 11159436 | pmc = 1301267 | doi = 10.1016/S0006-3495(01)76048-1 | bibcode = 2001BpJ....80..683S }}</ref></sup>
|
|-
|
* [[Inward-rectifier potassium channel|Voltage-gated]] (K<sub>ir</sub>2.x)
|
* final repolarization phase and stabilising the resting potential of the action potential in cardiac myocytes<ref>{{cite journal | vauthors = Dhamoon AS, Jalife J | title = The inward rectifier current (IK1) controls cardiac excitability and is involved in arrhythmogenesis | journal = Heart Rhythm | volume = 2 | issue = 3 | pages = 316–324 | date = March 2005 | pmid = 15851327 | doi = 10.1016/j.hrthm.2004.11.012 }}</ref>
|
* [[Chloroquine]]<ref name=":1">{{cite journal | vauthors = Swale DR, Kharade SV, Denton JS | title = Cardiac and renal inward rectifier potassium channel pharmacology: emerging tools for integrative physiology and therapeutics | journal = Current Opinion in Pharmacology | volume = 15 | pages = 7–15 | date = April 2014 | pmid = 24721648 | pmc = 4097192 | doi = 10.1016/j.coph.2013.11.002 }}</ref>
* [[Pentamidine]]<ref name=":1" />
* [https://www.sigmaaldrich.com/DE/de/product/mm/422689 ML133]<ref name=":1" />
* [[Fluoxetine]]<ref name=":1" />
* [[Nortriptyline|Nortryptiline]]<ref name=":1" />
* [[Dronedarone]]<ref>{{cite journal | vauthors = Xynogalos P, Seyler C, Scherer D, Koepple C, Scholz EP, Thomas D, Katus HA, Zitron E | display-authors = 6 | title = Class III antiarrhythmic drug dronedarone inhibits cardiac inwardly rectifying Kir2.1 channels through binding at residue E224 | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 387 | issue = 12 | pages = 1153–1161 | date = December 2014 | pmid = 25182566 | doi = 10.1007/s00210-014-1045-6 | s2cid = 10575229 }}</ref>
* [[Quinidine]]<ref>{{cite journal | vauthors = Koepple C, Scherer D, Seyler C, Scholz E, Thomas D, Katus HA, Zitron E | title = Dual Mechanism for Inhibition of Inwardly Rectifying Kir2.x Channels by Quinidine Involving Direct Pore Block and PIP<sub>2</sub>-interference | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 361 | issue = 2 | pages = 209–218 | date = May 2017 | pmid = 28188270 | doi = 10.1124/jpet.116.238287 | s2cid = 206502631 | doi-access = free }}</ref>
|
* [[Flecainide]]<ref name=":1" /><ref>{{cite journal | vauthors = Caballero R, Dolz-Gaitón P, Gómez R, Amorós I, Barana A, González de la Fuente M, Osuna L, Duarte J, López-Izquierdo A, Moraleda I, Gálvez E, Sánchez-Chapula JA, Tamargo J, Delpón E | display-authors = 6 | title = Flecainide increases Kir2.1 currents by interacting with cysteine 311, decreasing the polyamine-induced rectification | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 35 | pages = 15631–15636 | date = August 2010 | pmid = 20713726 | pmc = 2932566 | doi = 10.1073/pnas.1004021107 | doi-access = free | bibcode = 2010PNAS..10715631C }}</ref>
|-
|
*[[G protein-coupled inwardly-rectifying potassium channel|GPCR regulated]] (K<sub>ir</sub>3.x)
|
* mediate the inhibitory effect of many [[GPCR]]s
|
*[[Ifenprodil]]<ref name="pmid16123769">{{cite journal | vauthors = Kobayashi T, Washiyama K, Ikeda K | title = Inhibition of G protein-activated inwardly rectifying K+ channels by ifenprodil | journal = Neuropsychopharmacology | volume = 31 | issue = 3 | pages = 516–524 | date = March 2006 | pmid = 16123769 | doi = 10.1038/sj.npp.1300844 | doi-access = free }}</ref>
*[[Cloperastine]]<ref name="SoedaFujieda2016">{{cite journal | vauthors = Soeda F, Fujieda Y, Kinoshita M, Shirasaki T, Takahama K | title = Centrally acting non-narcotic antitussives prevent hyperactivity in mice: Involvement of GIRK channels | journal = Pharmacology, Biochemistry, and Behavior | volume = 144 | pages = 26–32 | date = May 2016 | pmid = 26892760 | doi = 10.1016/j.pbb.2016.02.006 | s2cid = 30118634 }}</ref><ref name="YAMAMOTOSOEDA2011">{{cite journal | vauthors = Yamamoto G, Soeda F, Shirasaki T, Takahama K | title = [Is the GIRK channel a possible target in the development of a novel therapeutic drug of urinary disturbance?] | journal = Yakugaku Zasshi | volume = 131 | issue = 4 | pages = 523–532 | date = April 2011 | pmid = 21467791 | doi = 10.1248/yakushi.131.523 | doi-access = free }}</ref><ref name="KAWAURAHONDA2010">{{cite journal | vauthors = Kawaura K, Honda S, Soeda F, Shirasaki T, Takahama K | title = [Novel antidepressant-like action of drugs possessing GIRK channel blocking action in rats] | journal = Yakugaku Zasshi | volume = 130 | issue = 5 | pages = 699–705 | date = May 2010 | pmid = 20460867 | doi = 10.1248/yakushi.130.699 | doi-access = free }}</ref>
*[[Tertiapin]]<ref name="Jinnovel">{{cite journal | vauthors = Jin W, Lu Z | title = A novel high-affinity inhibitor for inward-rectifier K+ channels | journal = Biochemistry | volume = 37 | issue = 38 | pages = 13291–13299 | date = September 1998 | pmid = 9748337 | doi = 10.1021/bi981178p }}</ref><ref name="Rang60" />
*[[Tipepidine]]<ref name="KawauraOgata2009">{{cite journal | vauthors = Kawaura K, Ogata Y, Inoue M, Honda S, Soeda F, Shirasaki T, Takahama K | title = The centrally acting non-narcotic antitussive tipepidine produces antidepressant-like effect in the forced swimming test in rats | journal = Behavioural Brain Research | volume = 205 | issue = 1 | pages = 315–318 | date = December 2009 | pmid = 19616036 | doi = 10.1016/j.bbr.2009.07.004 | s2cid = 29236491 | url = https://kumadai.repo.nii.ac.jp/record/24712/files/BBR_205_1_315-318.pdf }}</ref>
*[[Barium|Ba<sup>2+</sup>]]<ref name=":0" />
|
*[[ML-297|ML-297 (VU0456810)]]<ref>{{cite journal | vauthors = Kaufmann K, Romaine I, Days E, Pascual C, Malik A, Yang L, Zou B, Du Y, Sliwoski G, Morrison RD, Denton J, Niswender CM, Daniels JS, Sulikowski GA, Xie XS, Lindsley CW, Weaver CD | display-authors = 6 | title = ML297 (VU0456810), the first potent and selective activator of the GIRK potassium channel, displays antiepileptic properties in mice | journal = ACS Chemical Neuroscience | volume = 4 | issue = 9 | pages = 1278–1286 | date = September 2013 | pmid = 23730969 | pmc = 3778424 | doi = 10.1021/cn400062a }}</ref>
|-
|
*[[ATP-sensitive K+ channels|ATP-sensitive]] (K<sub>ir</sub>6.x)
|
* close when [[adenosine triphosphate|ATP]] is high to promote [[insulin]] secretion
|
*[[Acetohexamide]] {{Citation needed|date=May 2019}}
*[[Carbutamide]] {{Citation needed|date=May 2019}}
*[[Chlorpropamide]] {{Citation needed|date=May 2019}}
*[[Glibenclamide|Glibenclamide (glyburide)]]<ref name="pmid17015627">{{cite journal | vauthors = Serrano-Martín X, Payares G, Mendoza-León A | title = Glibenclamide, a blocker of K+(ATP) channels, shows antileishmanial activity in experimental murine cutaneous leishmaniasis | journal = Antimicrobial Agents and Chemotherapy | volume = 50 | issue = 12 | pages = 4214–4216 | date = December 2006 | pmid = 17015627 | pmc = 1693980 | doi = 10.1128/AAC.00617-06 }}</ref><ref name="Rang60" />
*[[Glibornuride]] {{Citation needed|date=May 2019}}
*[[Glicaramide]] {{Citation needed|date=May 2019}}
*[[Gliclazide]]<ref>{{cite journal | vauthors = Lawrence CL, Proks P, Rodrigo GC, Jones P, Hayabuchi Y, Standen NB, Ashcroft FM | title = Gliclazide produces high-affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells | journal = Diabetologia | volume = 44 | issue = 8 | pages = 1019–1025 | date = August 2001 | pmid = 11484080 | doi = 10.1007/s001250100595 | doi-access = free }}</ref>
*[[Glimepiride]] {{Citation needed|date=May 2019}}
*[[Glipizide]] {{Citation needed|date=May 2019}}
|{{Citation needed|date=May 2019}}

*[[Bimakalim]]
*[[Cromakalim]]
*[[Diazoxide]]<ref name="Rang60" />
*[[Levcromakalim]]
*[[Minoxidil]]<ref name="Rang60" />
*[[Nicorandil]]
*[[Pinacidil]]
|-
|[[Tandem pore domain potassium channel|Tandem pore domain]] <br /> 4[[transmembrane helix|T]] & 2[[pore-forming loop|P]]
|
* TWIK ([[KCNK1|TWIK-1]], [[KCNK6|TWIK-2]], [[KCNK7]])<ref name="pmid20393194">{{cite journal | vauthors = Enyedi P, Czirják G | title = Molecular background of leak K+ currents: two-pore domain potassium channels | journal = Physiological Reviews | volume = 90 | issue = 2 | pages = 559–605 | date = April 2010 | pmid = 20393194 | doi = 10.1152/physrev.00029.2009 | s2cid = 9358238 | url = http://repo.lib.semmelweis.hu//handle/123456789/8205 }}</ref><ref name="pmid17652773">{{cite journal | vauthors = Lotshaw DP | title = Biophysical, pharmacological, and functional characteristics of cloned and native mammalian two-pore domain K+ channels | journal = Cell Biochemistry and Biophysics | volume = 47 | issue = 2 | pages = 209–256 | year = 2007 | pmid = 17652773 | doi = 10.1007/s12013-007-0007-8 | s2cid = 12759521 }}</ref>
* TREK ([[KCNK2|TREK-1]], [[KCNK10|TREK-2]], [[KCNK4|TRAAK]]<ref name="pmid9628867">{{cite journal | vauthors = Fink M, Lesage F, Duprat F, Heurteaux C, Reyes R, Fosset M, Lazdunski M | title = A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids | journal = The EMBO Journal | volume = 17 | issue = 12 | pages = 3297–3308 | date = June 1998 | pmid = 9628867 | pmc = 1170668 | doi = 10.1093/emboj/17.12.3297 }}</ref>)<ref name="pmid20393194" /><ref name="pmid17652773" />
* TASK ([[KCNK3|TASK-1]], [[KCNK9|TASK-3]], [[KCNK15|TASK-5]])<ref name="pmid20393194" /><ref name="pmid17652773" />
* TALK ([[KCNK5|TASK-2]],<ref name="pmid11256078">{{cite journal | vauthors = Goldstein SA, Bockenhauer D, O'Kelly I, Zilberberg N | title = Potassium leak channels and the KCNK family of two-P-domain subunits | journal = Nature Reviews. Neuroscience | volume = 2 | issue = 3 | pages = 175–184 | date = March 2001 | pmid = 11256078 | doi = 10.1038/35058574 | s2cid = 9682396 | url = https://escholarship.org/uc/item/9z7112ns }}</ref> [[KCNK16|TALK-1]], [[KCNK17|TALK-2]])<ref name="pmid20393194" /><ref name="pmid17652773" />
* THIK ([[KCNK13|THIK-1]], [[KCNK12|THIK-2]])<ref name="pmid20393194" /><ref name="pmid17652773" />
*[[KCNK18|TRESK]]<ref name="pmid20393194" /><ref name="pmid17652773" /><ref name="pmid12754259">{{cite journal | vauthors = Sano Y, Inamura K, Miyake A, Mochizuki S, Kitada C, Yokoi H, Nozawa K, Okada H, Matsushime H, Furuichi K | display-authors = 6 | title = A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord | journal = The Journal of Biological Chemistry | volume = 278 | issue = 30 | pages = 27406–27412 | date = July 2003 | pmid = 12754259 | doi = 10.1074/jbc.M206810200 | doi-access = free }}</ref><ref name="pmid14981085">{{cite journal | vauthors = Czirják G, Tóth ZE, Enyedi P | title = The two-pore domain K+ channel, TRESK, is activated by the cytoplasmic calcium signal through calcineurin | journal = The Journal of Biological Chemistry | volume = 279 | issue = 18 | pages = 18550–18558 | date = April 2004 | pmid = 14981085 | doi = 10.1074/jbc.M312229200 | doi-access = free }}</ref>
|
* Contribute to [[resting potential]]
|
*[[bupivacaine]]<ref name="pmid10201682">{{cite journal | vauthors = Kindler CH, Yost CS, Gray AT | title = Local anesthetic inhibition of baseline potassium channels with two pore domains in tandem | journal = Anesthesiology | volume = 90 | issue = 4 | pages = 1092–1102 | date = April 1999 | pmid = 10201682 | doi = 10.1097/00000542-199904000-00024 | doi-access = free }}</ref><ref name="pmid11249964">{{cite journal | vauthors = Meadows HJ, Randall AD | title = Functional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel | journal = Neuropharmacology | volume = 40 | issue = 4 | pages = 551–559 | date = March 2001 | pmid = 11249964 | doi = 10.1016/S0028-3908(00)00189-1 | s2cid = 20181576 }}</ref><ref name="pmid12660311">{{cite journal | vauthors = Kindler CH, Paul M, Zou H, Liu C, Winegar BD, Gray AT, Yost CS | title = Amide local anesthetics potently inhibit the human tandem pore domain background K+ channel TASK-2 (KCNK5) | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 306 | issue = 1 | pages = 84–92 | date = July 2003 | pmid = 12660311 | doi = 10.1124/jpet.103.049809 | s2cid = 1621972 }}</ref><ref name="pmid12760993">{{cite journal | vauthors = Punke MA, Licher T, Pongs O, Friederich P | title = Inhibition of human TREK-1 channels by bupivacaine | journal = Anesthesia and Analgesia | volume = 96 | issue = 6 | pages = 1665–1673 | date = June 2003 | pmid = 12760993 | doi = 10.1213/01.ANE.0000062524.90936.1F | s2cid = 39630495 | doi-access = free }}</ref>
*[[quinidine]]<ref name="pmid11249964" /><ref name="pmid8605869">{{cite journal | vauthors = Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G, Barhanin J | title = TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure | journal = The EMBO Journal | volume = 15 | issue = 5 | pages = 1004–1011 | date = March 1996 | pmid = 8605869 | pmc = 449995 | doi = 10.1002/j.1460-2075.1996.tb00437.x }}</ref><ref name="pmid9312005">{{cite journal | vauthors = Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M | title = TASK, a human background K+ channel to sense external pH variations near physiological pH | journal = The EMBO Journal | volume = 16 | issue = 17 | pages = 5464–5471 | date = September 1997 | pmid = 9312005 | pmc = 1170177 | doi = 10.1093/emboj/16.17.5464 }}</ref><ref name="pmid9812978">{{cite journal | vauthors = Reyes R, Duprat F, Lesage F, Fink M, Salinas M, Farman N, Lazdunski M | title = Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney | journal = The Journal of Biological Chemistry | volume = 273 | issue = 47 | pages = 30863–30869 | date = November 1998 | pmid = 9812978 | doi = 10.1074/jbc.273.47.30863 | doi-access = free }}</ref><ref name="pmid10784345">{{cite journal | vauthors = Meadows HJ, Benham CD, Cairns W, Gloger I, Jennings C, Medhurst AD, Murdock P, Chapman CG | display-authors = 6 | title = Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel | journal = Pflügers Archiv | volume = 439 | issue = 6 | pages = 714–722 | date = April 2000 | pmid = 10784345 | doi = 10.1007/s004240050997 }}</ref>
*[[12-O-Tetradecanoylphorbol-13-acetate]]<ref>{{cite web|url=https://www.uniprot.org/uniprot/Q9NPC2|title=UniProtKB - Q9NPC2 (KCNK9_HUMAN)|publisher=[[Uniprot]]|access-date=2019-05-29}}</ref>
*[[Arachidonic acid]]{{citation needed|date=May 2019}}
*[[Fluoxetine]]<ref name="pmid156852122">{{cite journal | vauthors = Kennard LE, Chumbley JR, Ranatunga KM, Armstrong SJ, Veale EL, Mathie A | title = Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine | journal = British Journal of Pharmacology | volume = 144 | issue = 6 | pages = 821–829 | date = March 2005 | pmid = 15685212 | pmc = 1576064 | doi = 10.1038/sj.bjp.0706068 }}</ref>
*[[Norfluoxetine]]<ref name="pmid156852122" />
*Modulated by GPCR agonists and antagonists,<ref name="Rang60" />
*No selective blockers,<ref name="Rang60" />
|{{citation needed|date=May 2019}}

*[[halothane]]<ref name="pmid11249964" /><ref name="pmid10321245">{{cite journal | vauthors = Patel AJ, Honoré E, Lesage F, Fink M, Romey G, Lazdunski M | title = Inhalational anesthetics activate two-pore-domain background K+ channels | journal = Nature Neuroscience | volume = 2 | issue = 5 | pages = 422–426 | date = May 1999 | pmid = 10321245 | doi = 10.1038/8084 | s2cid = 23092576 }}</ref><ref name="pmid10839924">{{cite journal | vauthors = Gray AT, Zhao BB, Kindler CH, Winegar BD, Mazurek MJ, Xu J, Chavez RA, Forsayeth JR, Yost CS | display-authors = 6 | title = Volatile anesthetics activate the human tandem pore domain baseline K+ channel KCNK5 | journal = Anesthesiology | volume = 92 | issue = 6 | pages = 1722–1730 | date = June 2000 | pmid = 10839924 | doi = 10.1097/00000542-200006000-00032 | s2cid = 45487917 }}</ref>
*[[Riluzole]]
*Volatile anaesthetics, e.g. [[Isoflurane]]<ref name="Rang60" />
*Modulated by GPCR agonists and antagonists,<ref name="Rang60" />
|-
|[[Voltage-gated potassium channel|Voltage-gated]] <br /> 6[[transmembrane helix|T]] & 1[[pore-forming loop|P]]
|
*[[hERG]] (K<sub>v</sub>11.1)
*[[KvLQT1]] (K<sub>v</sub>7.1)
|
*[[action potential]] [[repolarization]]
* limits frequency of action potentials (disturbances cause [[Cardiac dysrhythmia|dysrhythmia]])
|
*[[3,4-Diaminopyridine|3,4-Diaminopyridine (amifampridine)]]<ref name="kirsch narahashi 1978">{{cite journal | vauthors = Kirsch GE, Narahashi T | title = 3,4-diaminopyridine. A potent new potassium channel blocker | journal = Biophysical Journal | volume = 22 | issue = 3 | pages = 507–512 | date = June 1978 | pmid = 667299 | pmc = 1473482 | doi = 10.1016/s0006-3495(78)85503-9 | bibcode = 1978BpJ....22..507K }}</ref>
*[[4-Aminopyridine|4-Aminopyridine (fampridine/dalfampridine)]]<ref name="pmid16472864"/><ref name="Rang60" />
*[[Bretylium]]<ref name="pmid1667290">{{cite journal | vauthors = Tiku PE, Nowell PT | title = Selective inhibition of K(+)-stimulation of Na,K-ATPase by bretylium | journal = British Journal of Pharmacology | volume = 104 | issue = 4 | pages = 895–900 | date = December 1991 | pmid = 1667290 | pmc = 1908819 | doi = 10.1111/j.1476-5381.1991.tb12523.x }}</ref>
*[[Tetraethylammonium]]<ref>{{cite journal | vauthors = Hille B | title = The selective inhibition of delayed potassium currents in nerve by tetraethylammonium ion | journal = The Journal of General Physiology | volume = 50 | issue = 5 | pages = 1287–1302 | date = May 1967 | pmid = 6033586 | pmc = 2225709 | doi = 10.1085/jgp.50.5.1287 }}</ref><ref name="Arm">{{cite journal | vauthors = Armstrong CM | title = Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons | journal = The Journal of General Physiology | volume = 58 | issue = 4 | pages = 413–437 | date = October 1971 | pmid = 5112659 | pmc = 2226036 | doi = 10.1085/jgp.58.4.413 }}</ref><ref name="Rang60" />
*'''[[hERG]] (KCNH2, K<sub>v</sub>11.1)-specific:'''
**[[Ajmaline]]{{citation needed|date=May 2019}}
**[[Amiodarone]]<ref>{{cite web|url=https://www.drugbank.ca/drugs/DB01118|title=Amiodarone|publisher=Drugbank|access-date=2019-05-28}}</ref>
**[[AmmTX3]]{{citation needed|date=May 2019}}
*'''[[KCNQ|KCNQ (K<sub>v</sub>7)]]-specific:''' [[Linopirdine]]
**[[Ssm spooky toxin]]{{citation needed|date=May 2019}}
|
*'''[[KCNQ|KCNQ (K<sub>v</sub>7)]]-specific:''' 
**[[Flupirtine]]
**[[Retigabine]] (K<sub>v</sub>7)<ref name="Rogawski">{{cite journal | vauthors = Rogawski MA, Bazil CW | title = New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels | journal = Current Neurology and Neuroscience Reports | volume = 8 | issue = 4 | pages = 345–352 | date = July 2008 | pmid = 18590620 | pmc = 2587091 | doi = 10.1007/s11910-008-0053-7 }}</ref>
|-
|}

== Structure ==
[[Image:Potassium channel1.png|thumb|250px|Top view of a potassium channel with potassium ions (purple) moving through the pore (in the center). ({{PDB|1BL8}})]]Potassium channels have a [[Tetrameric protein|tetramer]]ic structure in which four identical [[protein subunit]]s associate to form a fourfold [[symmetry|symmetric]] ([[Symmetry group#Two dimensions|C<sub>4</sub>]]) complex arranged around a central ion conducting pore (i.e., a homotetramer).  Alternatively four related but not identical protein subunits may associate to form heterotetrameric complexes with pseudo C<sub>4</sub> symmetry. All potassium channel subunits have a distinctive pore-loop structure that lines the top of the pore and is responsible for potassium selective permeability.

There are over 80 [[mammalian]] [[genes]] that encode potassium channel [[Protein subunit|subunit]]s.  However potassium channels found in [[bacterium|bacteria]] are amongst the most studied of ion channels, in terms of their molecular structure. Using [[X-ray crystallography]],<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><ref name="pmid9525854">{{cite journal | vauthors = MacKinnon R, Cohen SL, Kuo A, Lee A, Chait BT | title = Structural conservation in prokaryotic and eukaryotic potassium channels | journal = Science | volume = 280 | issue = 5360 | pages = 106–109 | date = April 1998 | pmid = 9525854 | doi = 10.1126/science.280.5360.106 | s2cid = 33907550 | bibcode = 1998Sci...280..106M }}</ref> profound insights have been gained into how potassium ions pass through these channels and why (smaller) [[sodium]] ions do not.<ref name="pmid9556453">{{cite journal | vauthors = Armstrong C | title = The vision of the pore | journal = Science | volume = 280 | issue = 5360 | pages = 56–57 | date = April 1998 | pmid = 9556453 | doi = 10.1126/science.280.5360.56 | s2cid = 35339674 }}</ref> The 2003 [[Nobel Prize for Chemistry]] was awarded to [[Roderick MacKinnon|Rod MacKinnon]] for his pioneering work in this area.<ref name="Nobel_Prize_2003">{{cite web | url =  http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/ | title = The Nobel Prize in Chemistry 2003 | access-date = 2007-11-16 | publisher = The Nobel Foundation }}</ref>

===Selectivity filter===
[[Image:1K4C.png|thumb|left|250px|'''Crystallographic structure of the bacterial [[KcsA potassium channel]] ({{PDB|1K4C}}).'''<ref name="pmid11689936">{{cite journal | vauthors = Zhou Y, Morais-Cabral JH, Kaufman A, MacKinnon R | title = Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution | journal = Nature | volume = 414 | issue = 6859 | pages = 43–48 | date = November 2001 | pmid = 11689936 | doi = 10.1038/35102009 | s2cid = 205022645 | bibcode = 2001Natur.414...43Z }}</ref> In this figure, only two of the four subunits of the tetramer are displayed for the sake of clarity. The protein is displayed as a green cartoon diagram. In addition backbone carbonyl groups and threonine sidechain protein atoms (oxygen = red, carbon = green) are displayed. Finally potassium ions (occupying the S2 and S4 sites) and the oxygen atoms of water molecules (S1 and S3) are depicted as purple and red spheres respectively.]]

Potassium ion channels remove the hydration shell from the ion when it enters the selectivity filter. The selectivity filter is formed by a five residue sequence, TVGYG, termed the signature sequence, within each of the four subunits. This signature sequence is within a loop between the pore helix and TM2/6, historically termed the P-loop. This signature sequence is highly conserved, with the exception that a valine residue in prokaryotic potassium channels is often substituted with an isoleucine residue in eukaryotic channels. This sequence adopts a unique main chain structure, structurally analogous to a [[nest (protein structural motif)|nest protein structural motif]]. The four sets of [[Electronegativity|electronegative]] [[Carbonyl group|carbonyl oxygen atoms]] are aligned toward the center of the filter pore and form a square antiprism similar to a water-solvating shell around each potassium binding site. The distance between the carbonyl oxygens and potassium ions in the binding sites of the selectivity filter is the same as between water oxygens in the first hydration shell and a potassium ion in water solution, providing an energetically-favorable route for de-[[solvation]] of the ions. Sodium ions, however, are too small to fill the space between the carbonyl oxygen atoms. Thus, it is energetically favorable for sodium ions to remain bound with water molecules in the extracellular space, rather than to pass through the potassium-selective ion pore.<ref>{{cite book | vauthors = Lodish H, Berk A, Kaiser C, Krieger M, Bretscher A, Ploegh H, Amon A, Martin K | display-authors = 6 |title=Molecular Cell Biology |date=2016 |publisher=W. H. Freeman and Company |location=New York, NY |isbn=978-1-4641-8339-3 |page=499 |edition=8th }}</ref> This width appears to be maintained by [[hydrogen bond]]ing and [[van der Waals force]]s within a sheet of aromatic amino acid residues surrounding the selectivity filter.<ref name="pmid9525859" /><ref>{{cite journal | vauthors = Sauer DB, Zeng W, Raghunathan S, Jiang Y | title = Protein interactions central to stabilizing the K+ channel selectivity filter in a four-sited configuration for selective K+ permeation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 40 | pages = 16634–16639 | date = October 2011 | pmid = 21933962 | pmc = 3189067 | doi = 10.1073/pnas.1111688108 | doi-access = free | bibcode = 2011PNAS..10816634S }}</ref> The selectivity filter opens towards the extracellular solution, exposing four carbonyl oxygens in a glycine residue (Gly79 in [[KcsA potassium channel|KcsA]]). The next residue toward the extracellular side of the protein is the negatively charged Asp80 (KcsA). This residue together with the five filter residues form the pore that connects the water-filled cavity in the center of the protein with the extracellular solution.<ref name="pmid16253415"/>

====Selectivity mechanism====
The mechanism of potassium channel selectivity remains under continued debate. The carbonyl oxygens are strongly electro-negative and cation-attractive. The filter can accommodate potassium ions at 4 sites usually labelled S1 to S4 starting at the extracellular side. In addition, one ion can bind in the cavity at a site called SC or one or more ions at the extracellular side at more or less well-defined sites called S0 or Sext. Several different occupancies of these sites are possible. Since the X-ray structures are averages over many molecules, it is, however, not possible to deduce the actual occupancies directly from such a structure. In general, there is some disadvantage due to electrostatic repulsion to have two neighboring sites occupied by ions. Proposals for the mechanism of selectivity have been made based on [[molecular dynamics]] simulations,<ref>{{cite journal | vauthors = Noskov SY, Roux B | title = Importance of hydration and dynamics on the selectivity of the KcsA and NaK channels | journal = The Journal of General Physiology | volume = 129 | issue = 2 | pages = 135–143 | date = February 2007 | pmid = 17227917 | pmc = 2154357 | doi = 10.1085/jgp.200609633 }}</ref> toy models of ion binding,<ref>{{cite journal | vauthors = Noskov SY, Bernèche S, Roux B | title = Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands | journal = Nature | volume = 431 | issue = 7010 | pages = 830–834 | date = October 2004 | pmid = 15483608 | doi = 10.1038/nature02943 | s2cid = 4414885 | bibcode = 2004Natur.431..830N }}</ref> thermodynamic calculations,<ref>{{cite journal | vauthors = Varma S, Rempe SB | title = Tuning ion coordination architectures to enable selective partitioning | journal = Biophysical Journal | volume = 93 | issue = 4 | pages = 1093–1099 | date = August 2007 | pmid = 17513348 | pmc = 1929028 | doi = 10.1529/biophysj.107.107482 | arxiv = physics/0608180 | bibcode = 2007BpJ....93.1093V }}</ref> topological considerations,<ref>{{cite journal | vauthors = Thomas M, Jayatilaka D, Corry B | title = The predominant role of coordination number in potassium channel selectivity | journal = Biophysical Journal | volume = 93 | issue = 8 | pages = 2635–2643 | date = October 2007 | pmid = 17573427 | pmc = 1989715 | doi = 10.1529/biophysj.107.108167 | bibcode = 2007BpJ....93.2635T }}</ref><ref>{{cite journal | vauthors = Bostick DL, Brooks CL | title = Selectivity in K+ channels is due to topological control of the permeant ion's coordinated state | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 22 | pages = 9260–9265 | date = May 2007 | pmid = 17519335 | pmc = 1890482 | doi = 10.1073/pnas.0700554104 | doi-access = free | bibcode = 2007PNAS..104.9260B }}</ref> and structural differences<ref>{{cite journal | vauthors = Derebe MG, Sauer DB, Zeng W, Alam A, Shi N, Jiang Y | title = Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 2 | pages = 598–602 | date = January 2011 | pmid = 21187421 | pmc = 3021048 | doi = 10.1073/pnas.1013636108 | doi-access = free | bibcode = 2011PNAS..108..598D }}</ref> between selective and non-selective channels.

The mechanism for ion translocation in KcsA has been studied extensively by theoretical calculations and simulation.<ref name="pmid16253415">{{cite journal | vauthors = Hellgren M, Sandberg L, Edholm O | title = A comparison between two prokaryotic potassium channels (KirBac1.1 and KcsA) in a molecular dynamics (MD) simulation study | journal = Biophysical Chemistry | volume = 120 | issue = 1 | pages = 1–9 | date = March 2006 | pmid = 16253415 | doi = 10.1016/j.bpc.2005.10.002 }}</ref><ref>{{cite journal | vauthors = Morais-Cabral JH, Zhou Y, MacKinnon R | title = Energetic optimization of ion conduction rate by the K+ selectivity filter | journal = Nature | volume = 414 | issue = 6859 | pages = 37–42 | date = November 2001 | pmid = 11689935 | doi = 10.1038/35102000 | s2cid = 4429890 | bibcode = 2001Natur.414...37M }}</ref> The prediction of an ion conduction mechanism in which the two doubly occupied states (S1, S3) and (S2, S4) play an essential role has been affirmed by both techniques. [[Molecular dynamics]] (MD) simulations suggest the two extracellular states, S<sub>ext</sub> and S<sub>0</sub>, reflecting ions entering and leaving the filter, also are important actors in ion conduction.

===Hydrophobic region===
This region neutralizes the environment around the potassium ion so that it is not attracted to any charges. In turn, it speeds up the reaction.

===Central cavity===
A central pore, 10 Å wide, is located near the center of the transmembrane channel, where the [[activation energy|energy barrier]] is highest for the transversing ion due to the hydrophobity of the channel wall. The water-filled cavity and the polar C-terminus of the pore helices ease the energetic barrier for the ion. Repulsion by preceding multiple potassium ions is thought to aid the throughput of the ions.
The presence of the cavity can be understood intuitively as one of the channel's mechanisms for overcoming the dielectric barrier, or repulsion by the low-dielectric membrane, by keeping the K<sup>+</sup> ion in a watery, high-dielectric environment.

==Regulation==
[[Image:038-PotassiumChannels.tiff|thumb|250px|Graphical representation of open and shut potassium channels ({{PDB|1lnq|}} and {{PDB|1k4c|}}). Two simple bacterial channels are shown to compare the "open" channel structure on the right with the "closed" structure on the left. At top is the filter (selects potassium ions), and at bottom is the gating domain (controls opening and closing of channel).]]
The flux of ions through the potassium channel pore is regulated by two related processes, termed [[Gating (electrophysiology)|gating]] and inactivation. Gating is the opening or closing of the channel in response to stimuli, while inactivation is the rapid cessation of current from an open potassium channel and the suppression of the channel's ability to resume conducting. While both processes serve to regulate channel conductance, each process may be mediated by a number of mechanisms.

Generally, gating is thought to be mediated by additional structural domains which sense stimuli and in turn open the channel pore. These domains include the RCK domains of BK channels,<ref name="ReferenceA">{{cite journal | vauthors = Yuan P, Leonetti MD, Pico AR, Hsiung Y, MacKinnon R | title = Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution | journal = Science | volume = 329 | issue = 5988 | pages = 182–186 | date = July 2010 | pmid = 20508092 | pmc = 3022345 | doi = 10.1126/science.1190414 | bibcode = 2010Sci...329..182Y }}</ref><ref name="ReferenceB">{{cite journal | vauthors = Wu Y, Yang Y, Ye S, Jiang Y | title = Structure of the gating ring from the human large-conductance Ca(2+)-gated K(+) channel | journal = Nature | volume = 466 | issue = 7304 | pages = 393–397 | date = July 2010 | pmid = 20574420 | pmc = 2910425 | doi = 10.1038/nature09252 | bibcode = 2010Natur.466..393W }}</ref><ref name="ReferenceC">{{cite journal | vauthors = Jiang Y, Pico A, Cadene M, Chait BT, MacKinnon R | title = Structure of the RCK domain from the E. coli K+ channel and demonstration of its presence in the human BK channel | journal = Neuron | volume = 29 | issue = 3 | pages = 593–601 | date = March 2001 | pmid = 11301020 | doi = 10.1016/S0896-6273(01)00236-7 | s2cid = 17880955 | doi-access = free }}</ref> and voltage sensor domains of voltage gated K<sup>+</sup> channels. These domains are thought to respond to the stimuli by physically opening the intracellular gate of the pore domain, thereby allowing potassium ions to traverse the membrane. Some channels have multiple regulatory domains or accessory proteins, which can act to modulate the response to stimulus. While the mechanisms continue to be debated, there are known structures of a number of these regulatory domains, including RCK domains of prokaryotic<ref>{{cite journal | vauthors = Jiang Y, Lee A, Chen J, Cadene M, Chait BT, MacKinnon R | title = Crystal structure and mechanism of a calcium-gated potassium channel | journal = Nature | volume = 417 | issue = 6888 | pages = 515–522 | date = May 2002 | pmid = 12037559 | doi = 10.1038/417515a | s2cid = 205029269 | bibcode = 2002Natur.417..515J }}</ref><ref>{{cite journal | vauthors = Kong C, Zeng W, Ye S, Chen L, Sauer DB, Lam Y, Derebe MG, Jiang Y | display-authors = 6 | title = Distinct gating mechanisms revealed by the structures of a multi-ligand gated K(+) channel | journal = eLife | volume = 1 | pages = e00184 | date = December 2012 | pmid = 23240087 | pmc = 3510474 | doi = 10.7554/eLife.00184 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Cao Y, Jin X, Huang H, Derebe MG, Levin EJ, Kabaleeswaran V, Pan Y, Punta M, Love J, Weng J, Quick M, Ye S, Kloss B, Bruni R, Martinez-Hackert E, Hendrickson WA, Rost B, Javitch JA, Rajashankar KR, Jiang Y, Zhou M | display-authors = 6 | title = Crystal structure of a potassium ion transporter, TrkH | journal = Nature | volume = 471 | issue = 7338 | pages = 336–340 | date = March 2011 | pmid = 21317882 | pmc = 3077569 | doi = 10.1038/nature09731 | bibcode = 2011Natur.471..336C }}</ref> and eukaryotic<ref name="ReferenceA"/><ref name="ReferenceB"/><ref name="ReferenceC"/> channels, pH gating domain of KcsA,<ref>{{cite journal | vauthors = Uysal S, Cuello LG, Cortes DM, Koide S, Kossiakoff AA, Perozo E | title = Mechanism of activation gating in the full-length KcsA K+ channel | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 29 | pages = 11896–11899 | date = July 2011 | pmid = 21730186 | pmc = 3141920 | doi = 10.1073/pnas.1105112108 | doi-access = free | bibcode = 2011PNAS..10811896U }}</ref> cyclic nucleotide gating domains,<ref>{{cite journal | vauthors = Clayton GM, Silverman WR, Heginbotham L, Morais-Cabral JH | title = Structural basis of ligand activation in a cyclic nucleotide regulated potassium channel | journal = Cell | volume = 119 | issue = 5 | pages = 615–627 | date = November 2004 | pmid = 15550244 | doi = 10.1016/j.cell.2004.10.030 | s2cid = 14149494 | doi-access = free }}</ref> and voltage gated potassium channels.<ref>{{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 | s2cid = 4347957 | bibcode = 2003Natur.423...33J }}</ref><ref>{{cite journal | vauthors = 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 | date = August 2005 | pmid = 16002581 | doi = 10.1126/science.1116269 | s2cid = 6072007 | bibcode = 2005Sci...309..897L | doi-access = free }}</ref>

N-type inactivation is typically the faster inactivation mechanism, and is termed the [[Ball and chain inactivation|"ball and chain" model]].<ref>{{cite journal | vauthors = Antz C, Fakler B | title = Fast Inactivation of Voltage-Gated K(+) Channels: From Cartoon to Structure | journal = News in Physiological Sciences | volume = 13 | issue = 4 | pages = 177–182 | date = August 1998 | pmid = 11390785 | doi = 10.1152/physiologyonline.1998.13.4.177 | s2cid = 38134756 }}</ref> N-type inactivation involves interaction of the N-terminus of the channel, or an associated protein, which interacts with the pore domain and occludes the ion conduction pathway like a "ball". Alternatively, C-type inactivation is thought to occur within the selectivity filter itself, where structural changes within the filter render it non-conductive. There are a number of structural models of C-type inactivated K<sup>+</sup> channel filters,<ref>{{cite journal | vauthors = Cheng WW, McCoy JG, Thompson AN, Nichols CG, Nimigean CM | title = Mechanism for selectivity-inactivation coupling in KcsA potassium channels | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 13 | pages = 5272–5277 | date = March 2011 | pmid = 21402935 | pmc = 3069191 | doi = 10.1073/pnas.1014186108 | doi-access = free | bibcode = 2011PNAS..108.5272C | author-link4 = Colin Nichols }}</ref><ref>{{cite journal | vauthors = Cuello LG, Jogini V, Cortes DM, Perozo E | title = Structural mechanism of C-type inactivation in K(+) channels | journal = Nature | volume = 466 | issue = 7303 | pages = 203–208 | date = July 2010 | pmid = 20613835 | pmc = 3033749 | doi = 10.1038/nature09153 | bibcode = 2010Natur.466..203C }}</ref><ref>{{cite journal | vauthors = Cuello LG, Jogini V, Cortes DM, Pan AC, Gagnon DG, Dalmas O, Cordero-Morales JF, Chakrapani S, Roux B, Perozo E | display-authors = 6 | title = Structural basis for the coupling between activation and inactivation gates in K(+) channels | journal = Nature | volume = 466 | issue = 7303 | pages = 272–275 | date = July 2010 | pmid = 20613845 | pmc = 3033755 | doi = 10.1038/nature09136 | bibcode = 2010Natur.466..272C }}</ref> although the precise mechanism remains unclear.

==Pharmacology==
===Blockers===
{{main|Potassium channel blocker}}
Potassium channel blockers inhibit the flow of potassium ions through the channel. They either compete with potassium binding within the selectivity filter or bind outside the filter to occlude ion conduction. An example of one of these competitors is quaternary ammonium ions, which bind at the extracellular face<ref name="Ions and blockers">{{cite journal | vauthors = Luzhkov VB, Aqvist J | title = Ions and blockers in potassium channels: insights from free energy simulations | journal = Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics | volume = 1747 | issue = 1 | pages = 109–120 | date = February 2005 | pmid = 15680245 | doi = 10.1016/j.bbapap.2004.10.006 }}</ref><ref name="Structure–activity relationship">{{cite journal | vauthors = Luzhkov VB, Osterberg F, Aqvist J | title = Structure-activity relationship for extracellular block of K+ channels by tetraalkylammonium ions | journal = FEBS Letters | volume = 554 | issue = 1–2 | pages = 159–164 | date = November 2003 | pmid = 14596932 | doi = 10.1016/S0014-5793(03)01117-7 | s2cid = 32031835 | doi-access = free | bibcode = 2003FEBSL.554..159L }}</ref> or central cavity of the channel.<ref>{{cite journal | vauthors = Posson DJ, McCoy JG, Nimigean CM | title = The voltage-dependent gate in MthK potassium channels is located at the selectivity filter | journal = Nature Structural & Molecular Biology | volume = 20 | issue = 2 | pages = 159–166 | date = February 2013 | pmid = 23262489 | pmc = 3565016 | doi = 10.1038/nsmb.2473 }}</ref> For blocking from the central cavity quaternary ammonium ions are also known as open channel blockers, as binding classically requires the prior opening of the cytoplasmic gate.<ref>{{cite journal | vauthors = Choi KL, Mossman C, Aubé J, Yellen G | title = The internal quaternary ammonium receptor site of Shaker potassium channels | journal = Neuron | volume = 10 | issue = 3 | pages = 533–541 | date = March 1993 | pmid = 8461140 | doi = 10.1016/0896-6273(93)90340-w | s2cid = 33361945 }}</ref>

[[Barium]] ions can also block potassium channel currents,<ref>{{cite journal | vauthors = Piasta KN, Theobald DL, Miller C | title = Potassium-selective block of barium permeation through single KcsA channels | journal = The Journal of General Physiology | volume = 138 | issue = 4 | pages = 421–436 | date = October 2011 | pmid = 21911483 | pmc = 3182450 | doi = 10.1085/jgp.201110684 }}</ref><ref>{{cite journal | vauthors = Neyton J, Miller C | title = Potassium blocks barium permeation through a calcium-activated potassium channel | journal = The Journal of General Physiology | volume = 92 | issue = 5 | pages = 549–567 | date = November 1988 | pmid = 3235973 | pmc = 2228918 | doi = 10.1085/jgp.92.5.549 }}</ref> by binding with high affinity within the selectivity filter.<ref>{{cite journal | vauthors = Lockless SW, Zhou M, MacKinnon R | title = Structural and thermodynamic properties of selective ion binding in a K+ channel | journal = PLOS Biology | volume = 5 | issue = 5 | pages = e121 | date = May 2007 | pmid = 17472437 | pmc = 1858713 | doi = 10.1371/journal.pbio.0050121 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Jiang Y, MacKinnon R | title = The barium site in a potassium channel by x-ray crystallography | journal = The Journal of General Physiology | volume = 115 | issue = 3 | pages = 269–272 | date = March 2000 | pmid = 10694255 | pmc = 2217209 | doi = 10.1085/jgp.115.3.269 }}</ref><ref>{{cite journal | vauthors = Lam YL, Zeng W, Sauer DB, Jiang Y | title = The conserved potassium channel filter can have distinct ion binding profiles: structural analysis of rubidium, cesium, and barium binding in NaK2K | journal = The Journal of General Physiology | volume = 144 | issue = 2 | pages = 181–192 | date = August 2014 | pmid = 25024267 | pmc = 4113894 | doi = 10.1085/jgp.201411191 }}</ref><ref>{{cite journal | vauthors = Guo R, Zeng W, Cui H, Chen L, Ye S | title = Ionic interactions of Ba2+ blockades in the MthK K+ channel | journal = The Journal of General Physiology | volume = 144 | issue = 2 | pages = 193–200 | date = August 2014 | pmid = 25024268 | pmc = 4113901 | doi = 10.1085/jgp.201411192 }}</ref> This tight binding is thought to underlie [[barium#Toxicity|barium toxicity]] by inhibiting potassium channel activity in excitable cells.

Medically [[potassium channel blocker]]s, such as [[4-aminopyridine]] and [[3,4-diaminopyridine]], have been investigated for the treatment of conditions such as [[multiple sclerosis]].<ref name="pmid16472864">{{cite journal | vauthors = Judge SI, Bever CT | title = Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment | journal = Pharmacology & Therapeutics | volume = 111 | issue = 1 | pages = 224–259 | date = July 2006 | pmid = 16472864 | doi = 10.1016/j.pharmthera.2005.10.006 }}</ref> [[Side effect|Off target]] drug effects can lead to drug induced [[Long QT syndrome]], a potentially life-threatening condition. This is most frequently due to action on the [[hERG]] potassium channel in the heart. Accordingly, all new drugs are preclinically tested for cardiac safety.

===Activators===
{{main|Potassium channel opener}}
{{expand section|date=May 2019}}

==Muscarinic potassium channel== <!--Muscarinic potassium channel redirects here-->
[[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.]]
{{see also|G protein-coupled inwardly-rectifying potassium channel}}

Some types of potassium channels are activated by [[muscarinic receptor]]s and these are called ''muscarinic potassium channels'' (I<sub>KACh</sub>).  These channels are a heterotetramer composed of two [[KCNJ3|GIRK1]] and two [[KCNJ5|GIRK4]] subunits.<ref name="pmid7877685">{{cite journal | vauthors = Krapivinsky G, Gordon EA, Wickman K, Velimirović B, Krapivinsky L, Clapham DE | title = The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins | journal = Nature | volume = 374 | issue = 6518 | pages = 135–141 | date = March 1995 | pmid = 7877685 | doi = 10.1038/374135a0 | s2cid = 4334467 | bibcode = 1995Natur.374..135K }}</ref><ref name="pmid9478984">{{cite journal | vauthors = Corey S, Krapivinsky G, Krapivinsky L, Clapham DE | title = Number and stoichiometry of subunits in the native atrial G-protein-gated K+ channel, IKACh | journal = The Journal of Biological Chemistry | volume = 273 | issue = 9 | pages = 5271–5278 | date = February 1998 | pmid = 9478984 | doi = 10.1074/jbc.273.9.5271 | doi-access = free }}</ref> Examples are potassium channels in the heart, which, when activated by [[parasympathetic]] signals through [[M2 receptors|M2 muscarinic receptors]], cause an outward current of potassium, which slows down the [[heart rate]].<ref name="pmid8521474">{{cite journal | vauthors = Kunkel MT, Peralta EG | title = Identification of domains conferring G protein regulation on inward rectifier potassium channels | journal = Cell | volume = 83 | issue = 3 | pages = 443–449 | date = November 1995 | pmid = 8521474 | doi = 10.1016/0092-8674(95)90122-1 | s2cid = 14720432 | doi-access = free }}</ref><ref name="pmid10414308">{{cite journal | vauthors = Wickman K, Krapivinsky G, Corey S, Kennedy M, Nemec J, Medina I, Clapham DE | title = Structure, G protein activation, and functional relevance of the cardiac G protein-gated K+ channel, IKACh | journal = Annals of the New York Academy of Sciences | volume = 868 | issue = 1 | pages = 386–398 | date = April 1999 | pmid = 10414308 | doi = 10.1111/j.1749-6632.1999.tb11300.x | url = http://www.annalsnyas.org/cgi/content/abstract/868/1/386 | url-status = dead | s2cid = 25949938 | bibcode = 1999NYASA.868..386W | archive-url = https://web.archive.org/web/20060129001228/http://www.annalsnyas.org/cgi/content/abstract/868/1/386 | archive-date = 2006-01-29 }}</ref>

== In fine art ==

[[Roderick MacKinnon]] commissioned ''Birth of an Idea'', a {{convert|5|ft|adj=on}} tall sculpture based on the KcsA potassium channel.<ref>{{cite journal | vauthors = Ball P |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 | name-list-style = vanc }}</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.
{{clear}}

== See also ==

* {{annotated link|Calcium channel}}
* {{annotated link|Inward-rectifier potassium ion channel}}
* {{annotated link|Potassium in biology}}
* {{annotated link|Potassium transporter family|Potassium transporter (Trk) family}}
* {{annotated link|Potassium uptake permease}}
* {{annotated link|Sodium ion channel}}
{{Clear}}

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

== External links ==
* {{Proteopedia|Potassium channel}} in 3D
* {{MeshName|Potassium+Channels}}
* {{cite web | url = http://neuromuscular.wustl.edu/mother/chan.html#k | title = Potassium Channels | access-date = 2008-03-10 | author = Neuromuscular Disease Center | date = 2008-03-04 | publisher = [[Washington University in St. Louis]] }}

{{Ion channels|g3}}
{{channel blockers}}

[[Category:Ion channels]]
[[Category:Electrophysiology]]
[[Category:Integral membrane proteins]]

Pages transcluded onto the current version of this page (help):

Calcium channel (edit)
Inward-rectifier potassium channel (edit)
Inward-rectifier potassium ion channel (edit)
Potassium in biology (edit)
Potassium transporter family (edit)
Potassium uptake permease (edit)
Sodium channel (edit)
Sodium ion channel (edit)
Template:Abbr (view source) (protected)
Template:Abbrlink (view source) (template editor protected)
Template:Ambox (view source) (template editor protected)
Template:Annotated link (view source) (template editor protected)
Template:Category handler (view source) (protected)
Template:Channel blockers (edit)
Template:Citation needed (view source) (protected)
Template:Cite book (view source) (protected)
Template:Cite journal (view source) (protected)
Template:Cite web (view source) (protected)
Template:Clear (view source) (protected)
Template:Convert (view source) (template editor protected)
Template:Delink (view source) (protected)
Template:Expand section (view source) (template editor protected)
Template:Fix (view source) (protected)
Template:Fix/category (view source) (protected)
Template:Hlist/styles.css (view source) (protected)
Template:Ion channel modulators (view source) (semi-protected)
Template:Ion channels (view source) (semi-protected)
Template:Main (view source) (template editor protected)
Template:Main other (view source) (protected)
Template:MeSH name (view source) (template editor protected)
Template:MeshName (view source) (template editor protected)
Template:Navbox (view source) (template editor protected)
Template:Navbox with collapsible groups (view source) (template editor protected)
Template:PDB (view source) (template editor protected)
Template:Pagetype (view source) (protected)
Template:Protected page maintenance message (view source) (template editor protected)
Template:Proteopedia (edit)
Template:Reflist (view source) (protected)
Template:Reflist/styles.css (view source) (protected)
Template:Replace (view source) (protected)
Template:SDcat (view source) (protected)
Template:See also (view source) (template editor protected)
Template:Short description (view source) (protected)
Template:Short description/lowercasecheck (view source) (protected)
Module:Annotated link (view source) (template editor protected)
Module:Arguments (view source) (protected)
Module:Category handler (view source) (protected)
Module:Category handler/blacklist (view source) (protected)
Module:Category handler/config (view source) (protected)
Module:Category handler/data (view source) (protected)
Module:Category handler/shared (view source) (protected)
Module:Check for unknown parameters (view source) (protected)
Module:Citation/CS1 (view source) (protected)
Module:Citation/CS1/COinS (view source) (protected)
Module:Citation/CS1/Configuration (view source) (protected)
Module:Citation/CS1/Date validation (view source) (protected)
Module:Citation/CS1/Identifiers (view source) (protected)
Module:Citation/CS1/Utilities (view source) (protected)
Module:Citation/CS1/Whitelist (view source) (protected)
Module:Citation/CS1/styles.css (view source) (protected)
Module:Convert (view source) (template editor protected)
Module:Convert/data (view source) (template editor protected)
Module:Convert/text (view source) (template editor protected)
Module:Delink (view source) (protected)
Module:Disambiguation/templates (view source) (protected)
Module:Format link (view source) (template editor protected)
Module:GetShortDescription (view source) (template editor protected)
Module:Hatnote (view source) (template editor protected)
Module:Hatnote/styles.css (view source) (template editor protected)
Module:Hatnote list (view source) (template editor protected)
Module:Labelled list hatnote (view source) (template editor protected)
Module:Lang (view source) (template editor protected)
Module:Lang/ISO 639 synonyms (view source) (template editor protected)
Module:Lang/data (view source) (template editor protected)
Module:Lang/data/iana languages (view source) (template editor protected)
Module:Lang/data/iana regions (view source) (template editor protected)
Module:Lang/data/iana scripts (view source) (template editor protected)
Module:Lang/data/iana suppressed scripts (view source) (template editor protected)
Module:Lang/data/iana variants (view source) (template editor protected)
Module:Message box (view source) (protected)
Module:Message box/ambox.css (view source) (protected)
Module:Message box/configuration (view source) (protected)
Module:Namespace detect/config (view source) (protected)
Module:Namespace detect/data (view source) (protected)
Module:Navbar (view source) (protected)
Module:Navbar/configuration (view source) (protected)
Module:Navbar/styles.css (view source) (protected)
Module:Navbox (view source) (template editor protected)
Module:Navbox/configuration (view source) (template editor protected)
Module:Navbox/styles.css (view source) (template editor protected)
Module:Navbox with collapsible groups (view source) (template editor protected)
Module:Navbox with collapsible groups/configuration (view source) (template editor protected)
Module:Pagetype (view source) (protected)
Module:Pagetype/config (view source) (protected)
Module:Pagetype/disambiguation (view source) (protected)
Module:Pagetype/rfd (view source) (protected)
Module:Pagetype/setindex (view source) (protected)
Module:Pagetype/softredirect (view source) (protected)
Module:SDcat (view source) (protected)
Module:String (view source) (protected)
Module:TableTools (view source) (protected)
Module:Unicode data (view source) (template editor protected)
Module:Unsubst (view source) (protected)
Module:Wikitext Parsing (view source) (protected)
Module:Yesno (view source) (protected)

Return to Potassium channel.

Retrieved from "https://en.wikipedia.org/wiki/Potassium_channel"