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Protein-coding gene in the species Homo sapiens
Potassium channel, subfamily K, member 13 (KCNK13 ), also known as K2P 13.1 or THIK-1, is a protein that in humans is encoded by the KCNK13 gene . It is a potassium channel containing two pore-forming P domains.[ 5] [ 6]
Ribbon structure of homodimeric two-pore potassium channel K2P13 (THIK-1).[ 7] K2P 13.1 was first discovered in 2000 from a rat cDNA library , along with the closely related protein K2P 12.1 [ 5] + channel 1 and 2 (THIK-1 and THIK-2) because the anesthetic halothane inhibited the potassium current. THIK-1 was also shown to be activated by arachidonic acid and displayed mild voltage dependence, with moderate outward rectification at low external K+ and weak inward rectification with nearly symmetrical K+ concentrations.[ 5] [ 8] G-protein-coupled receptor pathways[ 9] lipids such as PIP2 and oleoyl-CoA .[ 10]
In humans, THIK-1 expression is almost exclusively restricted to microglia , where it functions as the main potassium channel and is responsible for maintaining their resting membrane potential through tonic background potassium conductance.[ 11] NLRP3 inflammasome activation, and subsequent release of pro-inflammatory cytokine interleukin-1β (IL-1β) .[ 12] [ 13] [ 14] [ 15]
^ a b c GRCh38: Ensembl release 89: ENSG00000152315 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045404 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ a b c Rajan S, Wischmeyer E, Karschin C, Preisig-Müller R, Grzeschik KH, Daut J, et al. (March 2001). "THIK-1 and THIK-2, a novel subfamily of tandem pore domain K+ channels" . The Journal of Biological Chemistry . 276 (10): 7302– 7311. doi :10.1074/jbc.M008985200 PMID 11060316 . ^ 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 . ^ Rödström KE, Eymsh B, Proks P, Hayre MS, Madry C, Rowland A, et al. (2024-06-27). "CryoEM Structure of the human THIK-1 K2P K+ Channel Reveals a Lower 'Y-gate' Regulated by Lipids and Anaesthetics" bioRxiv . doi :10.1101/2024.06.26.600475 . Retrieved 2024-12-04 . ^ Aggarwal P, Singh S, Ravichandiran V (2021-08-01). "Two-Pore Domain Potassium Channel in Neurological Disorders" The Journal of Membrane Biology . 254 (4): 367– 380. doi :10.1007/s00232-021-00189-8 . ISSN 1432-1424 . PMID 34169340 . ^ Tateyama M, Kubo Y (2023-04-26). "Regulation of the two-pore domain potassium channel, THIK-1 and THIK-2, by G protein coupled receptors" . PLOS ONE . 18 (4): e0284962. Bibcode :2023PLoSO..1884962T . doi :10.1371/journal.pone.0284962 ISSN 1932-6203 . PMC 10132538 PMID 37099539 . ^ Riel EB, Jurs BC, Cordeiro S, Musinszki M, Schewe M, Baukrowitz T (2022-02-07). "The versatile regulation of K2P channels by polyanionic lipids of the phosphoinositide and fatty acid metabolism" . The Journal of General Physiology . 154 (2). doi :10.1085/jgp.202112989 . ISSN 0022-1295 . PMC 8693234 PMID 34928298 . ^ Rifat A, Ossola B, Burli RW, Dawson LA, Brice NL, Rowland A, et al. (2024-02-26). "Differential contribution of THIK-1 K+ channels and P2X7 receptors to ATP-mediated neuroinflammation by human microglia" . Journal of Neuroinflammation . 21 (1): 58. doi :10.1186/s12974-024-03042-6 ISSN 1742-2094 . PMC 10895799 PMID 38409076 . ^ Madry C, Kyrargyri V, Arancibia-Carcamo IL, Jolivet R, Kohsaka S, Bryan RM, et al. (January 2018). "Microglial Ramification, Surveillance, and Interleukin-1β Release Are Regulated by the Two-Pore Domain K+ Channel THIK-1" . Neuron . 97 (2): 299–312.e6. doi :10.1016/j.neuron.2017.12.002 . PMC 5783715 PMID 29290552 . ^ Xu Z, Chen ZM, Wu X, Zhang L, Cao Y, Zhou P (2020-12-07). "Distinct Molecular Mechanisms Underlying Potassium Efflux for NLRP3 Inflammasome Activation" . Frontiers in Immunology . 11 : 609441. doi :10.3389/fimmu.2020.609441 ISSN 1664-3224 . PMC 7793832 PMID 33424864 . ^ Drinkall S, Lawrence CB, Ossola B, Russell S, Bender C, Brice NB, et al. (2022). "The two pore potassium channel THIK-1 regulates NLRP3 inflammasome activation" . Glia . 70 (7): 1301– 1316. doi :10.1002/glia.24174 . ISSN 1098-1136 . PMC 9314991 PMID 35353387 . ^ Sakamaki K, Ishii TM, Sakata T, Takemoto K, Takagi C, Takeuchi A, et al. (2016-11-01). "Dysregulation of a potassium channel, THIK-1, targeted by caspase-8 accelerates cell shrinkage" Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1863 (11): 2766– 2783. doi :10.1016/j.bbamcr.2016.08.010 . ISSN 0167-4889 . PMID 27566292 .
Fearon IM, Campanucci VA, Brown ST, Hudasek K, O'Kelly IM, Nurse CA (2006). "Acute hypoxic regulation of recombinant THIK-1 stably expressed in HEK293 cells" . The Arterial Chemoreceptors . Advances in Experimental Medicine and Biology. Vol. 580. pp. 203– 8, discussion 351–9. doi :10.1007/0-387-31311-7_31 . ISBN 978-0-387-31310-8 PMID 16683720 . Goldstein SA, Bockenhauer D, O'Kelly I, Zilberberg N (Mar 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 . Theilig F, Goranova I, Hirsch JR, Wieske M, Unsal S, Bachmann S, et al. (2008). "Cellular localization of THIK-1 (K(2P)13.1) and THIK-2 (K(2P)12.1) K channels in the mammalian kidney" . Cellular Physiology and Biochemistry . 21 (1– 3): 63– 74. doi :10.1159/000113748 PMID 18209473 . Gierten J, Ficker E, Bloehs R, Schlomer K, Kathofer S, Scholz E, et al. (Aug 2008). "Regulation of two-pore-domain (K2P) potassium leak channels by the tyrosine kinase inhibitor genistein" . British Journal of Pharmacology . 154 (8): 1680– 1690. doi :10.1038/bjp.2008.213 . PMC 2518462 PMID 18516069 .
