Activation of potassium channels regulates excitability and can control the shape of the action potential waveform. They are present in all cells within the body and can influence processes as diverse as cognition, muscle contraction and hormone secretion. Potassium channels are subdivided into families, based on their structural and functional properties. The largest family consists of potassium channels that activated by membrane depolarization, with other families consisting of channels that are either activated by a rise of intracellular calcium ions or are constitutively active. A standardised nomenclature for potassium channels has been proposed by the NC-IUPHAR subcommittees on potassium channels [1-4], which has placed cloned channels into groups based on gene family and structure of channels that exhibit 6, 4 or 2 transmembrane domains (TM).

GtoImmuPdb View OFF Expand all nodes Collapse all nodes

* Key recommended reading is highlighted with an asterisk

* Aguilar-Bryan L, Clement JP, Gonzalez G, Kunjilwar K, Babenko A, Bryan J. (1998) Toward understanding the assembly and structure of KATP channels. Physiol. Rev., 78 (1): 227-45. [PMID:9457174]

Ahern CA, Kobertz WR. (2009) Chemical tools for K(+) channel biology. Biochemistry, 48 (3): 517-26. [PMID:19113860]

Ashcroft FM, Gribble FM. (1998) Correlating structure and function in ATP-sensitive K+ channels. Trends Neurosci., 21 (7): 288-94. [PMID:9683320]

Barrese V, Stott JB, Greenwood IA. (2018) KCNQ-Encoded Potassium Channels as Therapeutic Targets. Annu. Rev. Pharmacol. Toxicol., 58: 625-648. [PMID:28992433]

Bauer CK, Schwarz JR. (2001) Physiology of EAG K+ channels. J. Membr. Biol., 182 (1): 1-15. [PMID:11426295]

Bayliss DA, Barrett PQ. (2008) Emerging roles for two-pore-domain potassium channels and their potential therapeutic impact. Trends Pharmacol. Sci., 29 (11): 566-75. [PMID:18823665]

Bean BP. (2007) The action potential in mammalian central neurons. Nat. Rev. Neurosci., 8 (6): 451-65. [PMID:17514198]

Bezanilla F. (2000) The voltage sensor in voltage-dependent ion channels. Physiol. Rev., 80 (2): 555-92. [PMID:10747201]

* Borsotto M, Veyssiere J, Moha Ou Maati H, Devader C, Mazella J, Heurteaux C. (2015) Targeting two-pore domain K(+) channels TREK-1 and TASK-3 for the treatment of depression: a new therapeutic concept. Br. J. Pharmacol., 172 (3): 771-84. [PMID:25263033]

* Chang PC, Chen PS. (2015) SK channels and ventricular arrhythmias in heart failure. Trends Cardiovasc. Med., 25 (6): 508-14. [PMID:25743622]

Dalby-Brown W, Hansen HH, Korsgaard MP, Mirza N, Olesen SP. (2006) K(v)7 channels: function, pharmacology and channel modulators. Curr Top Med Chem, 6 (10): 999-1023. [PMID:16787276]

* Decher N, Kiper AK, Rinné S. (2017) Stretch-activated potassium currents in the heart: Focus on TREK-1 and arrhythmias. Prog. Biophys. Mol. Biol., 130 (Pt B): 223-232. [PMID:28526352]

Enyedi P, Czirják G. (2010) Molecular background of leak K+ currents: two-pore domain potassium channels. Physiol. Rev., 90 (2): 559-605. [PMID:20393194]

* Feliciangeli S, Chatelain FC, Bichet D, Lesage F. (2015) The family of K2P channels: salient structural and functional properties. J. Physiol. (Lond.), 593 (12): 2587-603. [PMID:25530075]

* Foster MN, Coetzee WA. (2016) KATP Channels in the Cardiovascular System. Physiol. Rev., 96 (1): 177-252. [PMID:26660852]

* Gada K, Plant LD. (2019) Two-pore domain potassium channels: emerging targets for novel analgesic drugs: IUPHAR Review 26. Br J Pharmacol, 176 (2): 256-266. [PMID:30325008]

* Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S. (2005) International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels. Pharmacol. Rev., 57 (4): 527-40. [PMID:16382106]

Goldstein SA, Bockenhauer D, O'Kelly I, Zilberberg N. (2001) Potassium leak channels and the KCNK family of two-P-domain subunits. Nat. Rev. Neurosci., 2 (3): 175-84. [PMID:11256078]

* Greene DL, Hoshi N. (2017) Modulation of Kv7 channels and excitability in the brain. Cell. Mol. Life Sci., 74 (3): 495-508. [PMID:27645822]

* Gutman GA, Chandy KG, Adelman JP, Aiyar J, Bayliss DA, Clapham DE, Covarriubias M, Desir GV, Furuichi K, Ganetzky B et al.. (2003) International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels. Pharmacol. Rev., 55 (4): 583-6. [PMID:14657415]

Hancox JC, McPate MJ, El Harchi A, Zhang YH. (2008) The hERG potassium channel and hERG screening for drug-induced torsades de pointes. Pharmacol. Ther., 119 (2): 118-32. [PMID:18616963]

Hansen JB. (2006) Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives. Curr. Med. Chem., 13 (4): 361-76. [PMID:16475928]

Honoré E. (2007) The neuronal background K2P channels: focus on TREK1. Nat. Rev. Neurosci., 8 (4): 251-61. [PMID:17375039]

Jenkinson DH. (2006) Potassium channels--multiplicity and challenges. Br. J. Pharmacol., 147 Suppl 1: S63-71. [PMID:16402122]

Judge SI, Bever CT. (2006) Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment. Pharmacol. Ther., 111 (1): 224-59. [PMID:16472864]

* Kaczmarek LK, Aldrich RW, Chandy KG, Grissmer S, Wei AD, Wulff H. (2017) International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels. Pharmacol. Rev., 69 (1): 1-11. [PMID:28267675]

Kaczorowski GJ, Garcia ML. (1999) Pharmacology of voltage-gated and calcium-activated potassium channels. Curr Opin Chem Biol, 3 (4): 448-58. [PMID:10419851]

Kannankeril P, Roden DM, Darbar D. (2010) Drug-induced long QT syndrome. Pharmacol. Rev., 62 (4): 760-81. [PMID:21079043]

Kobayashi T, Ikeda K. (2006) G protein-activated inwardly rectifying potassium channels as potential therapeutic targets. Curr. Pharm. Des., 12 (34): 4513-23. [PMID:17168757]

* Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA. (2005) International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels. Pharmacol. Rev., 57 (4): 509-26. [PMID:16382105]

* Latorre R, Castillo K, Carrasquel-Ursulaez W, Sepulveda RV, Gonzalez-Nilo F, Gonzalez C, Alvarez O. (2017) Molecular Determinants of BK Channel Functional Diversity and Functioning. Physiol. Rev., 97 (1): 39-87. [PMID:27807200]

Lawson K, McKay NG. (2006) Modulation of potassium channels as a therapeutic approach. Curr. Pharm. Des., 12 (4): 459-70. [PMID:16472139]

Lesage F. (2003) Pharmacology of neuronal background potassium channels. Neuropharmacology, 44 (1): 1-7. [PMID:12559116]

Lewis RJ, Garcia ML. (2003) Therapeutic potential of venom peptides. Nat Rev Drug Discov, 2 (10): 790-802. [PMID:14526382]

Lüscher C, Slesinger PA. (2010) Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease. Nat. Rev. Neurosci., 11 (5): 301-15. [PMID:20389305]

Mannhold R. (2006) Structure-activity relationships of K(ATP) channel openers. Curr Top Med Chem, 6 (10): 1031-47. [PMID:16787278]

Mathie A, Veale EL. (2007) Therapeutic potential of neuronal two-pore domain potassium-channel modulators. Curr Opin Investig Drugs, 8 (7): 555-62. [PMID:17659475]

Miller C. (2003) A charged view of voltage-gated ion channels. Nat. Struct. Biol., 10 (6): 422-4. [PMID:12768203]

Nardi A, Olesen SP. (2008) BK channel modulators: a comprehensive overview. Curr. Med. Chem., 15 (11): 1126-46. [PMID:18473808]

Nichols CG, Lopatin AN. (1997) Inward rectifier potassium channels. Annu. Rev. Physiol., 59: 171-91. [PMID:9074760]

* Niemeyer MI, Cid LP, González W, Sepúlveda FV. (2016) Gating, Regulation, and Structure in K2P K+ Channels: In Varietate Concordia?. Mol. Pharmacol., 90 (3): 309-17. [PMID:27268784]

Pongs O, Schwarz JR. (2010) Ancillary subunits associated with voltage-dependent K+ channels. Physiol. Rev., 90 (2): 755-96. [PMID:20393197]

* Poveda JA, Marcela Giudici A, Lourdes Renart M, Morales A, González-Ros JM. (2017) Towards understanding the molecular basis of ion channel modulation by lipids: Mechanistic models and current paradigms. Biochim. Biophys. Acta, 1859 (9 Pt B): 1507-1516. [PMID:28408206]

Reimann F, Ashcroft FM. (1999) Inwardly rectifying potassium channels. Curr. Opin. Cell Biol., 11 (4): 503-8. [PMID:10449331]

* Rifkin RA, Moss SJ, Slesinger PA. (2017) G Protein-Gated Potassium Channels: A Link to Drug Addiction. Trends Pharmacol. Sci., 38 (4): 378-392. [PMID:28188005]

Robbins J. (2001) KCNQ potassium channels: physiology, pathophysiology, and pharmacology. Pharmacol. Ther., 90 (1): 1-19. [PMID:11448722]

Salkoff L, Butler A, Ferreira G, Santi C, Wei A. (2006) High-conductance potassium channels of the SLO family. Nat. Rev. Neurosci., 7 (12): 921-31. [PMID:17115074]

Sanguinetti MC. (2000) Maximal function of minimal K+ channel subunits. Trends Pharmacol. Sci., 21 (6): 199-201. [PMID:10838601]

Seino S, Miki T. (2003) Physiological and pathophysiological roles of ATP-sensitive K+ channels. Prog. Biophys. Mol. Biol., 81 (2): 133-76. [PMID:12565699]

Stanfield PR, Nakajima S, Nakajima Y. (2002) Constitutively active and G-protein coupled inward rectifier K+ channels: Kir2.0 and Kir3.0. Rev. Physiol. Biochem. Pharmacol., 145: 47-179. [PMID:12224528]

Stocker M. (2004) Ca(2+)-activated K+ channels: molecular determinants and function of the SK family. Nat. Rev. Neurosci., 5 (10): 758-70. [PMID:15378036]

Takeda M, Tsuboi Y, Kitagawa J, Nakagawa K, Iwata K, Matsumoto S. (2011) Potassium channels as a potential therapeutic target for trigeminal neuropathic and inflammatory pain. Mol Pain, 7: 5. [PMID:21219657]

* Taylor KC, Sanders CR. (2017) Regulation of KCNQ/Kv7 family voltage-gated K⁺ channels by lipids. Biochim. Biophys. Acta, 1859 (4): 586-597. [PMID:27818172]

Trimmer JS, Rhodes KJ. (2004) Localization of voltage-gated ion channels in mammalian brain. Annu. Rev. Physiol., 66: 477-519. [PMID:14977411]

* Vivier D, Bennis K, Lesage F, Ducki S. (2016) Perspectives on the Two-Pore Domain Potassium Channel TREK-1 (TWIK-Related K(+) Channel 1). A Novel Therapeutic Target?. J. Med. Chem., 59 (11): 5149-57. [PMID:26588045]

Wang H, Tang Y, Wang L, Long CL, Zhang YL. (2007) ATP-sensitive potassium channel openers and 2,3-dimethyl-2-butylamine derivatives. Curr. Med. Chem., 14 (2): 133-55. [PMID:17266574]

Weatherall KL, Goodchild SJ, Jane DE, Marrion NV. (2010) Small conductance calcium-activated potassium channels: from structure to function. Prog. Neurobiol., 91 (3): 242-55. [PMID:20359520]

* Wei AD, Gutman GA, Aldrich R, Chandy KG, Grissmer S, Wulff H. (2005) International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels. Pharmacol. Rev., 57 (4): 463-72. [PMID:16382103]

Wickenden AD, McNaughton-Smith G. (2009) Kv7 channels as targets for the treatment of pain. Curr. Pharm. Des., 15 (15): 1773-98. [PMID:19442190]

Witchel HJ. (2007) The hERG potassium channel as a therapeutic target. Expert Opin. Ther. Targets, 11 (3): 321-36. [PMID:17298291]

Wulff H, Castle NA, Pardo LA. (2009) Voltage-gated potassium channels as therapeutic targets. Nat Rev Drug Discov, 8 (12): 982-1001. [PMID:19949402]

* Yang KC, Nerbonne JM. (2016) Mechanisms contributing to myocardial potassium channel diversity, regulation and remodeling. Trends Cardiovasc. Med., 26 (3): 209-18. [PMID:26391345]

Yellen G. (2002) The voltage-gated potassium channels and their relatives. Nature, 419 (6902): 35-42. [PMID:12214225]

Yu FH, Catterall WA. (2004) The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis. Sci. STKE, 2004 (253): re15. [PMID:15467096]

1. Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S. (2005) International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels. Pharmacol. Rev., 57 (4): 527-40. [PMID:16382106]

2. Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stühmer W et al.. (2005) International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacol. Rev., 57 (4): 473-508. [PMID:16382104]

3. Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA. (2005) International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels. Pharmacol. Rev., 57 (4): 509-26. [PMID:16382105]

4. Wei AD, Gutman GA, Aldrich R, Chandy KG, Grissmer S, Wulff H. (2005) International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels. Pharmacol. Rev., 57 (4): 463-72. [PMID:16382103]