KCNK9 explained

Potassium channel subfamily K member 9 is a protein that in humans is encoded by the KCNK9 gene.^{[1] [2] [3]}

This gene encodes K_2P9.1, 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] [4]} 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. ^[5]

Expression

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.^[6] TASK-3 channels are also expressed in the hippocampus; both on pyramidal cells and interneurons.^[7] It is thought that these channels may form heterodimers where their expressions co-localise.^{[8] [9]}

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.^{[10] [11]} 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.^[11]

See also

• Tandem pore domain potassium channel

Further reading

• Goldstein SA, Bockenhauer D, O'Kelly I, Zilberberg N . Potassium leak channels and the KCNK family of two-P-domain subunits. . Nat. Rev. Neurosci. . 2 . 3 . 175–84 . 2001 . 11256078 . 10.1038/35058574 . 9682396 .
• Rajan S, Wischmeyer E, Xin Liu G, Preisig-Müller R, Daut J, Karschin A, Derst C . TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histiding as pH sensor. . J. Biol. Chem. . 275 . 22 . 16650–7 . 2000 . 10747866 . 10.1074/jbc.M000030200 . free . 11858/00-001M-0000-0012-F930-0 . free .
• Chapman CG, Meadows HJ, Godden RJ, Campbell DA, Duckworth M, Kelsell RE, Murdock PR, Randall AD, Rennie GI, Gloger IS . 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 . 2001 . 11042359 . 10.1016/S0169-328X(00)00183-2 .
• Vega-Saenz de Miera E, Lau DH, Zhadina M, Pountney D, Coetzee WA, Rudy B . KT3.2 and KT3.3, two novel human two-pore K(+) channels closely related to TASK-1 . J. Neurophysiol. . 86 . 1 . 130–42 . 2001 . 11431495 . 10.1152/jn.2001.86.1.130. 14855672 .
• Talley EM, Bayliss DA . 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 . 2002 . 11886861 . 10.1074/jbc.M200502200 . free .
• Rajan S, Preisig-Müller R, Wischmeyer E, Nehring R, Hanley PJ, Renigunta V, Musset B, Schlichthörl G, Derst C, Karschin A, Daut J . Interaction with 14-3-3 proteins promotes functional expression of the potassium channels TASK-1 and TASK-3 . J. Physiol. . 545 . Pt 1 . 13–26 . 2003 . 12433946 . 2290646 . 10.1113/jphysiol.2002.027052 .
• 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 . Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene . Cancer Cell . 3 . 3 . 297–302 . 2003 . 12676587 . 10.1016/S1535-6108(03)00054-0 . free .
• Pei L, Wiser O, Slavin A, Mu D, Powers S, Jan LY, Hoey T . Oncogenic potential of TASK3 (Kcnk9) depends on K+ channel function . Proc. Natl. Acad. Sci. U.S.A. . 100 . 13 . 7803–7 . 2003 . 12782791 . 164668 . 10.1073/pnas.1232448100 . 2003PNAS..100.7803P . free .
• Rusznák Z, Pocsai K, Kovács I, Pór A, Pál B, Bíró T, Szücs G . 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 . 2004 . 15197476 . 10.1007/s00018-004-4082-3 . 11439105 . 11138546 .
• Clarke CE, Veale EL, Green PJ, Meadows HJ, Mathie A . Selective block of the human 2-P domain potassium channel, TASK-3, and the native leak potassium current, IKSO, by zinc . J. Physiol. . 560 . Pt 1 . 51–62 . 2005 . 15284350 . 1665210 . 10.1113/jphysiol.2004.070292 .
• Kim CJ, Cho YG, Jeong SW, Kim YS, Kim SY, Nam SW, Lee SH, Yoo NJ, Lee JY, Park WS . Altered expression of KCNK9 in colorectal cancers . APMIS . 112 . 9 . 588–94 . 2005 . 15601307 . 10.1111/j.1600-0463.2004.apm1120905.x . 41751315 .
• 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 . 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 . 2006 . 17013562 . 10.1007/s00018-006-6166-8 . 30705845 . 11136003 .
• Zuzarte M, Rinné S, Schlichthörl G, Schubert A, Daut J, Preisig-Müller R . A di-acidic sequence motif enhances the surface expression of the potassium channel TASK-3 . Traffic . 8 . 8 . 1093–100 . 2007 . 17547699 . 10.1111/j.1600-0854.2007.00593.x . 9662403 . free .

Notes and References

1. Kim Y, Bang H, Kim D . TASK-3, a new member of the tandem pore K(+) channel family . J Biol Chem . 275 . 13 . 9340–7 . May 2000 . 10734076 . 10.1074/jbc.275.13.9340 . free .
2. Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S . International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels . Pharmacol Rev . 57 . 4 . 527–40 . Dec 2005 . 16382106 . 10.1124/pr.57.4.12 . 7356601 .
3. Web site: Entrez Gene: KCNK9 potassium channel, subfamily K, member 9.
4. Web site: UniProtKB - Q9NPC2 (KCNK9_HUMAN). 2019-05-29. Uniprot.
5. Wilke. Bettina U.. Lindner. Moritz. Greifenberg. Lea. Albus. Alexandra. Kronimus. Yannick. Bünemann. Moritz. Leitner. Michael G.. Oliver. Dominik. 2014-11-25. Diacylglycerol mediates regulation of TASK potassium channels by Gq-coupled receptors. Nature Communications. En. 5. 1. 5540. 10.1038/ncomms6540. 25420509. 2014NatCo...5.5540W. 2041-1723. free.
6. Bayliss DA, Sirois JE, Talley EM . The TASK family: two-pore domain background K+ channels. . Molecular Interventions . 3 . 4 . 205–19 . June 2003 . 14993448 . 10.1124/mi.3.4.205 .
7. Torborg CL, Berg AP, Jeffries BW, Bayliss DA, McBain CJ . TASK-like conductances are present within hippocampal CA1 stratum oriens interneuron subpopulations. . The Journal of Neuroscience . 26 . 28 . 7362–7 . Jul 12, 2006 . 16837582 . 6674194 . 10.1523/jneurosci.1257-06.2006 .
8. Berg AP, Talley EM, Manger JP, Bayliss DA . Motoneurons express heteromeric TWIK-related acid-sensitive K+ (TASK) channels containing TASK-1 (KCNK3) and TASK-3 (KCNK9) subunits. . The Journal of Neuroscience . 24 . 30 . 6693–702 . Jul 28, 2004 . 15282272 . 6729708 . 10.1523/jneurosci.1408-04.2004 .
9. Kang D, Han J, Talley EM, Bayliss DA, Kim D . Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells. . The Journal of Physiology . 554 . Pt 1 . 64–77 . Jan 1, 2004 . 14678492 . 10.1113/jphysiol.2003.054387 . 1664745.
10. Linden AM, Aller MI, Leppä E, Rosenberg PH, Wisden W, Korpi ER . 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 . October 2008 . 18660435 . 10.1124/jpet.108.142083 . 31086459 .
11. Pang DS, Robledo CJ, Carr DR, Gent TC, Vyssotski AL, Caley A, Zecharia AY, Wisden W, Brickley SG, Franks NP . An unexpected role for TASK-3 potassium channels in network oscillations with implications for sleep mechanisms and anesthetic action. . Proceedings of the National Academy of Sciences of the United States of America . 106 . 41 . 17546–51 . Oct 13, 2009 . 19805135 . 10.1073/pnas.0907228106 . 2751655 . 2009PNAS..10617546P . free .