The 4TM family of K channels mediate many of the background potassium currents observed in native cells. They are open across the physiological voltage-range and are regulated by a wide array of neurotransmitters and biochemical mediators. The pore-forming α-subunit contains two pore loop (P) domains and two subunits assemble to form one ion conduction pathway lined by four P domains. It is important to note that single channels do not have two pores but that each subunit has two P domains in its primary sequence; hence the name two-pore domain, or K_2P channels (and not two-pore channels). Some of the K_2P subunits can form heterodimers across subfamilies (e.g. K_2P3.1 with K_2P9.1). The nomenclature of 4TM K channels in the literature is still a mixture of IUPHAR and common names. The suggested division into subfamilies, described in the More detailed introduction, is based on similarities in both structural and functional properties within subfamilies and this explains the "common abbreviation" nomenclature in the tables below.

The K_2P6, K_2P7.1, K_2P15.1 and K_2P12.1 subtypes, when expressed in isolation, are nonfunctional. All 4TM channels are insensitive to the classical potassium channel blockers tetraethylammonium and fampridine, but are blocked to varying degrees by Ba²⁺ ions.

* Key recommended reading is highlighted with an asterisk

* 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]

* Jin X, Zhang Y, Alharbi A, Hanbashi A, Alhoshani A, Parrington J. (2020) Targeting Two-Pore Channels: Current Progress and Future Challenges. Trends Pharmacol Sci, 41 (8): 582-594. [PMID:32679067]

* Mathie A, Veale EL, Cunningham KP, Holden RG, Wright PD. (2021) Two-Pore Domain Potassium Channels as Drug Targets: Anesthesia and Beyond. Annu Rev Pharmacol Toxicol, 61: 401-420. [PMID:32679007]

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Subcommittee members: Steve A.N. Goldstein (Chairperson) Departments of Pediatrics Physiology & Biophysics, and Pharmaceutical Sciences University of California, Irvine 1001 Health Sciences Road Irvine Hall 265 Irvine, CA 92697-3950 USA Leigh D. Plant Research Associate Professor Department of Pharmaceutical Sciences Northeastern University, School of Pharmacy Bouvé College of Health Sciences 360 Huntington Avenue Boston, MA 02115 USA

Other contributors: Austin M. Baggetta Department of Pharmaceutical Sciences Northeastern University, School of Pharmacy Bouvé College of Health Sciences 360 Huntington Avenue Boston, MA 02115 USA Douglas A. Bayliss Department of Pharmacology University of Virginia Health System Charlottesville VA 22908 USA Gábor Czirják Department of Physiology Semmelweis University Budapest Hungary Péter Enyedi Department of Physiology Semmelweis University Budapest Hungary Florian Lesage CNRS UMR 7275 Université de Nice Valbonne France Daniel L. Minor, Jr. Cardiovascular Research Institute Departments of Biochemistry & Biophysics and Cellular & Molecular Pharmacology California Institute for Quantitative Biomedical Research Kavli Institute for Fundamental Neuroscience University of California, San Francisco CA, U.S.A. Francisco Sepúlveda Centro de Estudios Científicos Valdivia Chile