Potassium channel subfamily K member 9 is a protein that in humans is encoded by the KCNK9gene.[1][2][3]
This gene encodes K2P9.1, one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. This open channel is highly expressed in the cerebellum. It is inhibited by extracellular acidification and arachidonic acid, and strongly inhibited by phorbol 12-myristate 13-acetate.[3] Phorbol 12-myristate 13-acetate is also known as 12-O-tetradecanoylphorbol-13-acetate (TPA). TASK channels are additionally inhibited by hormones and transmitters that signal through GqPCRs. The resulting cellular depolarization is thought to regulate processes such as motor control and aldosterone secretion. Despite early controversy about the exact mechanism underlying this inhibition, the current view is that Diacyl-glycerol, produced by the breakdown of Phosphatidylinositol-4,5-bis-phosphate by Phospholipase Cβ causes channel closure. [4]
The KCNK9 gene is expressed as an ion channel more commonly known as TASK 3. This channel has a varied pattern of expression. TASK 3 is coexpressed with TASK 1 (KCNK3) in the cerebellar granule cells, locus coeruleus, motor neurons, pontine nuclei, some cells in the neocortex, habenula, olfactory bulb granule cells, and cells in the external plexiform layer of the olfactory bulb.[5] TASK-3 channels are also expressed in the hippocampus; both on pyramidal cells and interneurons.[6] It is thought that these channels may form heterodimers where their expressions co-localise.[7][8]
Function
Mice in which the TASK-3 gene has been deleted have reduced sensitivity to inhalation anaesthetics, exaggerated nocturnal activity and cognitive deficits as well as significantly increased appetite and weight gain.[9][10] A role for TASK-3 channels in neuronal network oscillations has also been described: TASK-3 knockout mice lack the atropine-sensitive halothane-induced theta oscillation (4–7 Hz) from the hippocampus and are unable to maintain theta oscillations during rapid eye movement (REM) sleep.[10]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
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↑Kim Y, Bang H, Kim D (May 2000). "TASK-3, a new member of the tandem pore K(+) channel family". J Biol Chem. 275 (13): 9340–7. doi:10.1074/jbc.275.13.9340. PMID10734076.
↑Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S (Dec 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. PMID16382106.
↑Linden AM, Aller MI, Leppä E, Rosenberg PH, Wisden W, Korpi ER (October 2008). "K+ channel TASK-1 knockout mice show enhanced sensitivities to ataxic and hypnotic effects of GABA(A) receptor ligands". The Journal of Pharmacology and Experimental Therapeutics. 327 (1): 277–86. doi:10.1124/jpet.108.142083. PMID18660435.
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. PMID11256078.
Rajan S, Wischmeyer E, Xin Liu G, Preisig-Müller R, Daut J, Karschin A, Derst C (2000). "TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histiding as pH sensor". J. Biol. Chem. 275 (22): 16650–7. doi:10.1074/jbc.M000030200. PMID10747866.
Chapman CG, Meadows HJ, Godden RJ, Campbell DA, Duckworth M, Kelsell RE, Murdock PR, Randall AD, Rennie GI, Gloger IS (2001). "Cloning, localisation and functional expression of a novel human, cerebellum specific, two pore domain potassium channel". Brain Res. Mol. Brain Res. 82 (1–2): 74–83. doi:10.1016/S0169-328X(00)00183-2. PMID11042359.
Vega-Saenz de Miera E, Lau DH, Zhadina M, Pountney D, Coetzee WA, Rudy B (2001). "KT3.2 and KT3.3, two novel human two-pore K(+) channels closely related to TASK-1". J. Neurophysiol. 86 (1): 130–42. PMID11431495.
Talley EM, Bayliss DA (2002). "Modulation of TASK-1 (Kcnk3) and TASK-3 (Kcnk9) potassium channels: volatile anesthetics and neurotransmitters share a molecular site of action". J. Biol. Chem. 277 (20): 17733–42. doi:10.1074/jbc.M200502200. PMID11886861.
Mu D, Chen L, Zhang X, See LH, Koch CM, Yen C, Tong JJ, Spiegel L, Nguyen KC, Servoss A, Peng Y, Pei L, Marks JR, Lowe S, Hoey T, Jan LY, McCombie WR, Wigler MH, Powers S (2003). "Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene". Cancer Cell. 3 (3): 297–302. doi:10.1016/S1535-6108(03)00054-0. PMID12676587.
Rusznák Z, Pocsai K, Kovács I, Pór A, Pál B, Bíró T, Szücs G (2004). "Differential distribution of TASK-1, TASK-2 and TASK-3 immunoreactivities in the rat and human cerebellum". Cell. Mol. Life Sci. 61 (12): 1532–42. doi:10.1007/s00018-004-4082-3. PMID15197476.
Kim CJ, Cho YG, Jeong SW, Kim YS, Kim SY, Nam SW, Lee SH, Yoo NJ, Lee JY, Park WS (2005). "Altered expression of KCNK9 in colorectal cancers". APMIS. 112 (9): 588–94. doi:10.1111/j.1600-0463.2004.apm1120905.x. PMID15601307.
Pocsai K, Kosztka L, Bakondi G, Gönczi M, Fodor J, Dienes B, Szentesi P, Kovács I, Feniger-Barish R, Kopf E, Zharhary D, Szucs G, Csernoch L, Rusznák Z (2006). "Melanoma cells exhibit strong intracellular TASK-3-specific immunopositivity in both tissue sections and cell culture". Cell. Mol. Life Sci. 63 (19–20): 2364–76. doi:10.1007/s00018-006-6166-8. PMID17013562.
Zuzarte M, Rinné S, Schlichthörl G, Schubert A, Daut J, Preisig-Müller R (2007). "A di-acidic sequence motif enhances the surface expression of the potassium channel TASK-3". Traffic. 8 (8): 1093–100. doi:10.1111/j.1600-0854.2007.00593.x. PMID17547699.
