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Gene Review

KCNK2  -  potassium channel, two pore domain...

Homo sapiens

Synonyms: K2p2.1, Outward rectifying potassium channel protein TREK-1, Potassium channel subfamily K member 2, TPKC1, TREK, ...
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Disease relevance of KCNK2

  • Interestingly, hypoxia is unable to regulate alkalotic inhibition of TREK1 suggesting that this channel may be more intimately involved in control of excitability during physiological or pathological alkalosis [1].
  • Hypoxia represents a potent inhibitory influence on both channel types and occludes the activation by arachidonic acid, intracellular acidosis and membrane deformation of TREK1 [1].
  • This casts doubt on the idea that TREK1 activation during brain ischemia might facilitate neuroprotection via hyperpolarising neurons in which it is expressed [1].
  • Thus it seems likely that hTREK1 regulation in the brain will be physiologically more relevant during alkalosis than during ischemia or acidosis [2].
  • OBJECTIVE: Evaluate the time of incubation to detect positive blood cultures from newborn infants with suspected sepsis using a computer-assisted, automated blood culture system, ESP (Trek Diagnostic Systems, Inc, Westlake, OH) [3].

High impact information on KCNK2

  • Previously attributed to distinct transport pathways, we demonstrate here that phosphorylation of single, native hippocampal and cloned KCNK2 potassium channels produces reversible interconversion between leak and voltage-dependent phenotypes [4].
  • Chloroform, diethyl ether, halothane and isoflurane activated TREK-1, whereas only halothane and isoflurane activated TASK [5].
  • TREK-1 knockout mice have impaired PUFA-mediated neuroprotection to ischemia, reduced sensitivity to volatile anesthetics and altered perception of pain [6].
  • Inhibition of TREK-1/AKAP150 by Gq-coupled receptors such as serotonin 5HT2bR and glutamate mGluR5 is much reduced when compared to TREK-1 alone [6].
  • Inhibition of the TREK-1/AKAP150 complex by Gs-coupled receptors such as serotonin 5HT4sR and noradrenaline beta2AR is as extensive as for TREK-1 alone, but is faster [6].

Chemical compound and disease context of KCNK2


Biological context of KCNK2


Anatomical context of KCNK2


Associations of KCNK2 with chemical compounds

  • TREK-1 currents are insensitive to pharmacological agents that block TWIK-1 activity such as quinine and quinidine [15].
  • Overall, these results establish the identity of I(AC) K(+) channels, demonstrate the expression of bTREK-1 in a specific endocrine cell, identify potent new TREK-1 antagonists, and assign a pivotal role for these tandem-pore channels in the physiology of cortisol secretion [17].
  • TREK-1 is a mechanosensitive member of the two-pore domain potassium channel family (2PK+) that is also sensitive to lipids, free fatty acids (including arachidonic acid), temperature, intracellular pH, and a range of clinically relevant compounds including volatile anaesthetics [13].
  • The recent demonstration that TASK-1 and TREK-1 channels are activated by inhalational general anesthetics, and that TRAAK is activated by the neuroprotective agent riluzole, indicates that this novel class of K(+) channels is an interesting target for new therapeutic developments [18].
  • Block of TREK-1 by fluoxetine may have important consequences when the drug is used clinically in the treatment of depression [19].

Other interactions of KCNK2

  • For TREK1, TASK1 and TASK3 channels, PIP2 hydrolysis underlies inhibition by several agonists [14].
  • TWIK-2, TREK-1 and TREK-2 showed no significant change in expression at 3 days but showed large decreases at 3 weeks and 3 months following deafness [20].
  • 5. Progressive deletion of the C-terminus of TREK-1 had no effect on the inhibition of the channel by fluoxetine [19].
  • CH activation of hTREK-1 was transient followed by a rapid inhibition, whereas hTRAAK activation was not followed by inhibition [21].
  • The human tandem P domain K+ channel hTREK-1 (KCNK2) is distributed widely through the CNS [22].

Analytical, diagnostic and therapeutic context of KCNK2


  1. Regulation of recombinant human brain tandem P domain K+ channels by hypoxia: a role for O2 in the control of neuronal excitability? Kemp, P.J., Peers, C., Lewis, A., Miller, P. J. Cell. Mol. Med. (2004) [Pubmed]
  2. Polymodal regulation of hTREK1 by pH, arachidonic acid, and hypoxia: physiological impact in acidosis and alkalosis. Miller, P., Peers, C., Kemp, P.J. Am. J. Physiol., Cell Physiol. (2004) [Pubmed]
  3. Rapid detection of microorganisms in blood cultures of newborn infants utilizing an automated blood culture system. Garcia-Prats, J.A., Cooper, T.R., Schneider, V.F., Stager, C.E., Hansen, T.N. Pediatrics (2000) [Pubmed]
  4. KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel. Bockenhauer, D., Zilberberg, N., Goldstein, S.A. Nat. Neurosci. (2001) [Pubmed]
  5. Inhalational anesthetics activate two-pore-domain background K+ channels. Patel, A.J., Honoré, E., Lesage, F., Fink, M., Romey, G., Lazdunski, M. Nat. Neurosci. (1999) [Pubmed]
  6. AKAP150, a switch to convert mechano-, pH- and arachidonic acid-sensitive TREK K(+) channels into open leak channels. Sandoz, G., Th??mmler, S., Duprat, F., Feliciangeli, S., Vinh, J., Escoubas, P., Guy, N., Lazdunski, M., Lesage, F. EMBO J. (2006) [Pubmed]
  7. The lipid-activated two-pore domain K+ channel TREK-1 is resistant to hypoxia: implication for ischaemic neuroprotection. Buckler, K.J., Honoré, E. J. Physiol. (Lond.) (2005) [Pubmed]
  8. Comparison of the ESP and BACTEC systems for testing susceptibilities of Mycobacterium tuberculosis complex isolates to pyrazinamide. LaBombardi, V.J. J. Clin. Microbiol. (2002) [Pubmed]
  9. Inhibition of human TREK-1 channels by bupivacaine. Punke, M.A., Licher, T., Pongs, O., Friederich, P. Anesth. Analg. (2003) [Pubmed]
  10. Inhibition of human TREK-1 channels by caffeine and theophylline. Harinath, S., Sikdar, S.K. Epilepsy Res. (2005) [Pubmed]
  11. Mapping of human potassium channel genes TREK-1 (KCNK2) and TASK (KCNK3) to chromosomes 1q41 and 2p23. Lesage, F., Lazdunski, M. Genomics (1998) [Pubmed]
  12. Sequential phosphorylation mediates receptor- and kinase-induced inhibition of TREK-1 background potassium channels. Murbartián, J., Lei, Q., Sando, J.J., Bayliss, D.A. J. Biol. Chem. (2005) [Pubmed]
  13. Expression of the mechanosensitive 2PK+ channel TREK-1 in human osteoblasts. Hughes, S., Magnay, J., Foreman, M., Publicover, S.J., Dobson, J.P., El Haj, A.J. J. Cell. Physiol. (2006) [Pubmed]
  14. PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels. Lopes, C.M., Rohács, T., Czirják, G., Balla, T., Enyedi, P., Logothetis, D.E. J. Physiol. (Lond.) (2005) [Pubmed]
  15. Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. Fink, M., Duprat, F., Lesage, F., Reyes, R., Romey, G., Heurteaux, C., Lazdunski, M. EMBO J. (1996) [Pubmed]
  16. Localization of TASK and TREK, two-pore domain K+ channels, in human cytotrophoblast cells. Bai, X., Greenwood, S.L., Glazier, J.D., Baker, P.N., Sibley, C.P., Taggart, M.J., Fyfe, G.K. J. Soc. Gynecol. Investig. (2005) [Pubmed]
  17. An ACTH- and ATP-regulated background K+ channel in adrenocortical cells is TREK-1. Enyeart, J.J., Xu, L., Danthi, S., Enyeart, J.A. J. Biol. Chem. (2002) [Pubmed]
  18. Molecular and functional properties of two-pore-domain potassium channels. Lesage, F., Lazdunski, M. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  19. Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine. Kennard, L.E., Chumbley, J.R., Ranatunga, K.M., Armstrong, S.J., Veale, E.L., Mathie, A. Br. J. Pharmacol. (2005) [Pubmed]
  20. Deafness associated changes in expression of two-pore domain potassium channels in the rat cochlear nucleus. Holt, A.G., Asako, M., Keith Duncan, R., Lomax, C.A., Juiz, J.M., Altschuler, R.A. Hear. Res. (2006) [Pubmed]
  21. Trichloroethanol enhances the activity of recombinant human TREK-1 and TRAAK channels. Harinath, S., Sikdar, S.K. Neuropharmacology (2004) [Pubmed]
  22. Acute hypoxia occludes hTREK-1 modulation: re-evaluation of the potential role of tandem P domain K+ channels in central neuroprotection. Miller, P., Kemp, P.J., Lewis, A., Chapman, C.G., Meadows, H.J., Peers, C. J. Physiol. (Lond.) (2003) [Pubmed]
  23. Expression of TASK and TREK, two-pore domain K+ channels, in human myometrium. Bai, X., Bugg, G.J., Greenwood, S.L., Glazier, J.D., Sibley, C.P., Baker, P.N., Taggart, M.J., Fyfe, G.K. Reproduction (2005) [Pubmed]
  24. The two-pore-domain K(+) channels TREK-1 and TASK-3 are differentially modulated by copper and zinc. Gruss, M., Mathie, A., Lieb, W.R., Franks, N.P. Mol. Pharmacol. (2004) [Pubmed]
  25. Expression pattern and functional characteristics of two novel splice variants of the two-pore-domain potassium channel TREK-2. Gu, W., Schlichthörl, G., Hirsch, J.R., Engels, H., Karschin, C., Karschin, A., Derst, C., Steinlein, O.K., Daut, J. J. Physiol. (Lond.) (2002) [Pubmed]
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