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 aprotein that in humans is encoded by theKCNK13 gene . It is apotassium 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 ratcDNA library , along with the closely related proteinK2P 12.1 [ 5] + channel 1 and 2 (THIK-1 and THIK-2) because theanesthetic halothane inhibited the potassium current. THIK-1 was also shown to be activated byarachidonic acid and displayed mild voltage dependence, with moderate outward rectification at low external K+ and weakinward rectification with nearly symmetrical K+ concentrations.[ 5] [ 8] G-protein-coupled receptor pathways[ 9] lipids such asPIP2 andoleoyl-CoA .[ 10]
In humans, THIK-1 expression is almost exclusively restricted tomicroglia , where it functions as the mainpotassium channel and is responsible for maintaining theirresting membrane potential through tonic background potassium conductance.[ 11] NLRP3 inflammasome activation, and subsequent release of pro-inflammatory cytokineinterleukin-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, Karschin A, Derst C (March 2001)."THIK-1 and THIK-2, a novel subfamily of tandem pore domain K+ channels" .J. Biol. Chem .276 (10):7302– 11.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" .Pharmacol. Rev .57 (4):527– 40.doi :10.1124/pr.57.4.12 .PMID 16382106 .S2CID 7356601 . ^ Rödström KE, Eymsh B, Proks P, Hayre MS, Madry C, Rowland A, Newstead S, Baukrowitz T, Schewe M (2024-06-27),CryoEM Structure of the human THIK-1 K2P K+ Channel Reveals a Lower 'Y-gate' Regulated by Lipids and Anaesthetics doi :10.1101/2024.06.26.600475 , retrieved2024-12-04 ^ 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, Jürs 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" .Journal of General Physiology .154 (2).doi :10.1085/jgp.202112989 .ISSN 0022-1295 .PMC 8693234 PMID 34928298 . ^ Rifat A, Ossola B, Bürli RW, Dawson LA, Brice NL, Rowland A, Lizio M, Xu X, Page K, Fidzinski P, Onken J, Holtkamp M, Heppner FL, Geiger JR, Madry C (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-Cárcamo IL, Jolivet R, Kohsaka S, Bryan RM, Attwell D (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 .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, Dawson LA, Harte M, Brough D (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, Morishita R, Takahashi H, Nozawa A, Shinoda H, Chiba K, Sugimoto H, Saito A, Tamate S, Satou Y (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 . Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD (2002)."Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences" .Proc. Natl. Acad. Sci. U.S.A .99 (26):16899– 903.Bibcode :2002PNAS...9916899M .doi :10.1073/pnas.242603899 PMC 139241 PMID 12477932 . 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 (2001)."Potassium leak channels and the KCNK family of two-P-domain subunits" .Nat. Rev. Neurosci .2 (3):175– 84.doi :10.1038/35058574 .PMID 11256078 .S2CID 9682396 . Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R (2004)."The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)" .Genome Res .14 (10B):2121– 7.doi :10.1101/gr.2596504 .PMC 528928 PMID 15489334 . Theilig F, Goranova I, Hirsch JR, Wieske M, ÜNsal S, Bachmann S, Veh RW, Derst C (2008)."Cellular localization of THIK-1 (K(2P)13.1) and THIK-2 (K(2P)12.1) K channels in the mammalian kidney" .Cell. Physiol. Biochem .21 (1– 3):63– 74.doi :10.1159/000113748 PMID 18209473 . Gierten J, Ficker E, Bloehs R, Schlömer K, Kathöfer S, Scholz E, Zitron E, Kiesecker C, Bauer A (2008)."Regulation of two-pore-domain (K2P) potassium leak channels by the tyrosine kinase inhibitor genistein" .Br. J. Pharmacol .154 (8):1680– 90.doi :10.1038/bjp.2008.213 .PMC 2518462 PMID 18516069 .
