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 Goldman-Hodgkin-Katz (open) rectification.[1] These channels are regulated by several mechanisms including signaling lipids, oxygen tension, pH, mechanical stretch, and G-proteins.[2] 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 α-helices, a pore helix and a potassium ion selectivity filter sequence and assembles into a tetramer forming the complete channel.[3] The two-pore domain potassium channels instead are dimers where each subunit is essentially two α-subunits joined together.[4]

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.[5] To quote Rang and Dale (2015), "The nomenclature is misleading, especially when they are incorrectly referred to as two-pore channels".[6]

Below is a list of the 15 known two-pore-domain human potassium channels:[1]

GeneChannel[7]FamilyAliases
KCNK1K2p1.1TWIK[2][8]TWIK-1
KCNK2K2p2.1TREK[2][8]TREK-1
KCNK3K2p3.1TASK[2][8]TASK-1
KCNK4K2p4.1TREK[2][8]TRAAK[9]
KCNK5K2p5.1TASK[2][8]TASK-2[10]
KCNK6K2p6.1TWIK[2][8]TWIK-2
KCNK7K2p7.1TWIK[2][8]
KCNK9K2p9.1TASK[2][8]TASK-3
KCNK10K2p10.1TREK[2][8]TREK-2
KCNK12K2p12.1THIKTHIK-2
KCNK13K2p13.1THIKTHIK-1
KCNK15K2p15.1TASK[2][8]TASK-5
KCNK16K2p16.1TALK[2][8]TALK-1
KCNK17K2p17.1TALK[2][8]TALK-2, TASK-4
KCNK18K2p18.1TRIK, TRESK[2][8][11][12]
K2P1
Human K2P1 PDB: 3UKM​
Identifiers
SymbolK2P1
HGNC6272
RefSeqNP_002236.1
UniProtO00180
Search for
StructuresSwiss-model
DomainsInterPro
K2P2
Human K2P2 PDB: 4TWK​
Identifiers
SymbolK2P2
HGNC6277
RefSeqNP_055032.1
UniProtO95069
Search for
StructuresSwiss-model
DomainsInterPro
K2P3
Human K2P3 PDB: 6RV3​
Identifiers
SymbolK2P3
HGNC6278
RefSeqNP_002237.1
UniProtO14649
Search for
StructuresSwiss-model
DomainsInterPro

See also

References

  1. 1 2 Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S (December 2005). "International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels". Pharmacological Reviews. 57 (4): 527–540. doi:10.1124/pr.57.4.12. PMID 16382106. S2CID 7356601.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Enyedi P, Czirják G (April 2010). "Molecular background of leak K+ currents: two-pore domain potassium channels". Physiological Reviews. 90 (2): 559–605. doi:10.1152/physrev.00029.2009. PMID 20393194.
  3. ↑ Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, et al. (April 1998). "The structure of the potassium channel: molecular basis of K+ conduction and selectivity". Science. 280 (5360): 69–77. Bibcode:1998Sci...280...69D. doi:10.1126/science.280.5360.69. PMID 9525859.
  4. ↑ Miller AN, Long SB (January 2012). "Crystal structure of the human two-pore domain potassium channel K2P1". Science. 335 (6067): 432–436. Bibcode:2012Sci...335..432M. doi:10.1126/science.1213274. PMID 22282804. S2CID 206537279.
  5. ↑ Baggetta AM, Bayliss DA, Czirják G, Enyedi P, Goldstein SA, Lesage F, Minor Jr DL, Plant LD, Sepúlveda F. "Two P domain potassium channels". GtoPdb v.2023.1. IUPHAR/BPS Guide to Pharmacology. Retrieved 2019-05-28.
  6. ↑ Rang HP (2003). Pharmacology (8 ed.). Edinburgh: Churchill Livingstone. p. 59. ISBN 978-0-443-07145-4.
  7. ↑ Gutman GA, Chandy KG, Adelman JP, Aiyar J, Bayliss DA, Clapham DE, et al. (December 2003). "International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels". Pharmacological Reviews. 55 (4): 583–586. doi:10.1124/pr.55.4.9. PMID 14657415. S2CID 34963430.
  8. 1 2 3 4 5 6 7 8 9 10 11 12 13 Lotshaw DP (2007). "Biophysical, pharmacological, and functional characteristics of cloned and native mammalian two-pore domain K+ channels". Cell Biochemistry and Biophysics. 47 (2): 209–256. doi:10.1007/s12013-007-0007-8. PMID 17652773. S2CID 12759521.
  9. ↑ Fink M, Lesage F, Duprat F, Heurteaux C, Reyes R, Fosset M, Lazdunski M (June 1998). "A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids". The EMBO Journal. 17 (12): 3297–3308. doi:10.1093/emboj/17.12.3297. PMC 1170668. PMID 9628867.
  10. ↑ Goldstein SA, Bockenhauer D, O'Kelly I, Zilberberg N (March 2001). "Potassium leak channels and the KCNK family of two-P-domain subunits". Nature Reviews. Neuroscience. 2 (3): 175–184. doi:10.1038/35058574. PMID 11256078. S2CID 9682396.
  11. ↑ Sano Y, Inamura K, Miyake A, Mochizuki S, Kitada C, Yokoi H, et al. (July 2003). "A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord". The Journal of Biological Chemistry. 278 (30): 27406–27412. doi:10.1074/jbc.M206810200. PMID 12754259.
  12. ↑ Czirják G, Tóth ZE, Enyedi P (April 2004). "The two-pore domain K+ channel, TRESK, is activated by the cytoplasmic calcium signal through calcineurin". The Journal of Biological Chemistry. 279 (18): 18550–18558. doi:10.1074/jbc.M312229200. PMID 14981085.
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