View source for Two-pore-domain potassium channel

{{Short description|Class of transport proteins}}
{{distinguish|text=the small family of [[two-pore channel]]s}}
The '''two-pore-domain''' or '''tandem pore domain potassium channels''' are a family of 15 members that form what is known as '''leak channels''' which possess [[GHK current equation|Goldman-Hodgkin-Katz]] (open) [[rectifier|rectification]].<ref name="Goldstein">{{cite journal | vauthors = Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S | title = International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 527–540 | date = December 2005 | pmid = 16382106 | doi = 10.1124/pr.57.4.12 | s2cid = 7356601 | url = https://escholarship.org/uc/item/3k15p5vt }}</ref> These channels are regulated by several mechanisms including [[lipid-gated ion channels|signaling lipids]], [[oxygen tension]], [[pH]], [[mechanical stretch]], and [[G-protein]]s.<ref name="pmid20393194" /> Two-pore-domain potassium channels correspond structurally to a [[inward-rectifier potassium channel]] α-subunits. Each inward-rectifier potassium channel α-subunit is composed of two [[Transmembrane protein|transmembrane]] α-helices, a pore helix and a potassium ion selectivity filter sequence and assembles into a [[Tetrameric protein|tetramer]] forming the complete channel.<ref>{{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> The two-pore domain potassium channels instead are [[Protein dimer|dimers]] where each subunit is essentially two α-subunits joined together.<ref>{{cite journal | vauthors = Miller AN, Long SB | title = Crystal structure of the human two-pore domain potassium channel K2P1 | journal = Science | volume = 335 | issue = 6067 | pages = 432–436 | date = January 2012 | pmid = 22282804 | doi = 10.1126/science.1213274 | bibcode = 2012Sci...335..432M | s2cid = 206537279 }}</ref>
Each single channel does ''not'' have two pores; the name of the channel comes from the fact that ''each subunit'' has two P (pore) domains in its primary sequence.<ref>{{cite web | vauthors = Baggetta AM, Bayliss DA, Czirják G, Enyedi P, Goldstein SA, Lesage F, Minor Jr DL, Plant LD, Sepúlveda F | work = GtoPdb v.2023.1. IUPHAR/BPS [[Guide to Pharmacology]] |url=http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=79|access-date=2019-05-28|title=Two P domain potassium channels }}</ref> To quote Rang and Dale (2015), "The nomenclature is misleading, especially when they are incorrectly referred to as two-pore channels".<ref name="Rang60">{{cite book|title=Pharmacology| vauthors = Rang HP |publisher=Churchill Livingstone|year=2003|isbn=978-0-443-07145-4|edition=8|location=Edinburgh|page=59}}</ref>
A decrease in these leak channels activity is known as 'channel arrest', which reduces oxygen consumption<ref>{{Cite journal |last1=Lutz |first1=Peter L. |last2=Milton |first2=Sarah L. |date=2004-08-15 |title=Negotiating brain anoxia survival in the turtle |url=https://journals.biologists.com/jeb/article/207/18/3141/9334/Negotiating-brain-anoxia-survival-in-the-turtle |journal=Journal of Experimental Biology |language=en |volume=207 |issue=18 |pages=3141–3147 |doi=10.1242/jeb.01056 |issn=1477-9145}}</ref> and allows animals to survive anoxia.<ref>{{Cite journal |last1=Welker |first1=Alexis F. |last2=Moreira |first2=Daniel C. |last3=Campos |first3=Élida G. |last4=Hermes-Lima |first4=Marcelo |date=August 2013 |title=Role of redox metabolism for adaptation of aquatic animals to drastic changes in oxygen availability |url=https://linkinghub.elsevier.com/retrieve/pii/S1095643313000986 |journal=Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology |language=en |volume=165 |issue=4 |pages=384–404 |doi=10.1016/j.cbpa.2013.04.003|pmid=23587877 }}</ref>
Below is a list of the 15 known two-pore-domain human [[potassium channel]]s:<ref name="Goldstein"/>
{| class="sortable wikitable"
| '''Gene''' || '''Channel'''<ref name="pmid14657415">{{cite journal | vauthors = Gutman GA, Chandy KG, Adelman JP, Aiyar J, Bayliss DA, Clapham DE, Covarriubias M, Desir GV, Furuichi K, Ganetzky B, Garcia ML, Grissmer S, Jan LY, Karschin A, Kim D, Kuperschmidt S, Kurachi Y, Lazdunski M, Lesage F, Lester HA, McKinnon D, Nichols CG, O'Kelly I, Robbins J, Robertson GA, Rudy B, Sanguinetti M, Seino S, Stuehmer W, Tamkun MM, Vandenberg CA, Wei A, Wulff H, Wymore RS | display-authors = 6 | title = International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels | journal = Pharmacological Reviews | volume = 55 | issue = 4 | pages = 583–586 | date = December 2003 | pmid = 14657415 | doi = 10.1124/pr.55.4.9 | s2cid = 34963430 }}</ref> || '''Family''' || '''Aliases'''
|-
| {{Gene|KCNK1}} || [[KCNK1|K<sub>2p</sub>1.1]] || TWIK<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 | 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> || TWIK-1
|-
| {{Gene|KCNK2}} || [[KCNK2|K<sub>2p</sub>2.1]] || TREK<ref name="pmid20393194"/><ref name="pmid17652773"/> || TREK-1
|-
| {{Gene|KCNK3}} || [[KCNK3|K<sub>2p</sub>3.1]] || TASK<ref name="pmid20393194"/><ref name="pmid17652773"/> || TASK-1
|-
| {{Gene|KCNK4}} || [[KCNK4|K<sub>2p</sub>4.1]] ||  TREK<ref name="pmid20393194"/><ref name="pmid17652773"/> || 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>
|-
| {{Gene|KCNK5}} || [[KCNK5|K<sub>2p</sub>5.1]] || TASK<ref name="pmid20393194"/><ref name="pmid17652773"/> || 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>
|-
| {{Gene|KCNK6}} || [[KCNK6|K<sub>2p</sub>6.1]] || TWIK<ref name="pmid20393194"/><ref name="pmid17652773"/> || TWIK-2
|-
| {{Gene|KCNK7}} || [[KCNK7|K<sub>2p</sub>7.1]] || TWIK<ref name="pmid20393194"/><ref name="pmid17652773"/> ||
|-
| {{Gene|KCNK9}} || [[KCNK9|K<sub>2p</sub>9.1]] || TASK<ref name="pmid20393194"/><ref name="pmid17652773"/> || TASK-3
|-
| {{Gene|KCNK10}} || [[KCNK10|K<sub>2p</sub>10.1]] || TREK<ref name="pmid20393194"/><ref name="pmid17652773"/> || TREK-2
|-
| {{Gene|KCNK12}} || [[KCNK12|K<sub>2p</sub>12.1]] || THIK || THIK-2
|-
| {{Gene|KCNK13}} || [[KCNK13|K<sub>2p</sub>13.1]] || THIK || THIK-1
|-
| {{Gene|KCNK15}} || [[KCNK15|K<sub>2p</sub>15.1]] || TASK<ref name="pmid20393194"/><ref name="pmid17652773"/> || TASK-5
|-
| {{Gene|KCNK16}} || [[KCNK16|K<sub>2p</sub>16.1]] || TALK<ref name="pmid20393194"/><ref name="pmid17652773"/> || TALK-1
|-
| {{Gene|KCNK17}} || [[KCNK17|K<sub>2p</sub>17.1]] || TALK<ref name="pmid20393194"/><ref name="pmid17652773"/> || TALK-2, TASK-4
|-
| {{Gene|KCNK18}} || [[KCNK18|K<sub>2p</sub>18.1]] ||  || TRIK, 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>
|}
{|
|-
|{{Infobox protein
| name       = K2P1
| UniProt    = O00180
| HGNCid     = 6272
| RefSeq     = NP_002236.1
| Symbol     = K2P1
| image      = File:Two-pore domain potassium channel K2P1 PDB-3ukm.png
| caption    = Human K2P1 {{PDB|3UKM}}
}}
|{{Infobox protein
| name       = K2P2
| UniProt    = O95069
| HGNCid     = 6277
| RefSeq     = NP_055032.1
| Symbol     = K2P2
| image      = File:Two-pore domain potassium channel K2P2 PDB-4twk.png
| caption    = Human K2P2 {{PDB|4TWK}}
}}
|{{Infobox protein
| name       = K2P3
| UniProt    = O14649
| HGNCid     = 6278
| RefSeq     = NP_002237.1
| Symbol     = K2P3
| image      = File:Two-pore domain potassium channel K2P3 PDB-6rv3.png
| caption    = Human K2P3 {{PDB|6RV3}}
}}
|}
== See also ==
* [[Ion channel]]
* [[Potassium channel]]
== References ==
{{Reflist|33em}}
== External links ==
* {{MeshName|Tandem+Pore+Domain+Potassium+Channel}}
* {{cite web | url = http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=79 | title = Two-P Potassium Channels | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology }}
{{Ion channels|g3}}
{{ion channel modulators}}
{{protein-stub}}
[[Category:Ion channels]]