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Gene Review

Kcnk2  -  potassium channel, subfamily K, member 2

Mus musculus

Synonyms: A430027H14Rik, AI848635, Outward rectifying potassium channel protein TREK-1, Potassium channel subfamily K member 2, TREK-1, ...
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Disease relevance of Kcnk2


High impact information on Kcnk2

  • TREK-1 knockout mice have impaired PUFA-mediated neuroprotection to ischemia, reduced sensitivity to volatile anesthetics and altered perception of pain [4].
  • 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 [4].
  • TREK-1 is highly expressed in small sensory neurons, is present in both peptidergic and nonpeptidergic neurons and is extensively colocalized with TRPV1, the capsaicin-activated nonselective ion channel [5].
  • 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 [4].
  • Protonation of E306 drastically tightens channel-phospholipid interaction and leads to TREK-1 opening at atmospheric pressure [2].

Biological context of Kcnk2


Anatomical context of Kcnk2

  • TREK-1 is a two-pore-domain background potassium channel expressed throughout the central nervous system [1].
  • Unlike TWIK-1, TREK-1 and TASK which are widely distributed in many different mouse tissues, TRAAK is present exclusively in brain, spinal cord and retina [9].
  • TREK-1 encodes a component of the stretch-activated K(+) conductance in smooth muscles and may contribute to nitrergic inhibition of gastrointestinal muscles [10].
  • Whole cell currents from TREK-1 expressed in mammalian COS cells were activated by stretch, and single channel recordings showed that the stretch-dependent conductance was due to 90 pS channels [10].
  • Conversely, the actin cytoskeleton tonically represses TREK-1 mechano-sensitivity [11].

Associations of Kcnk2 with chemical compounds


Regulatory relationships of Kcnk2

  • Here, we show that the expression of TREK-1 markedly alters the cytoskeletal network and induces the formation of actin- and ezrin-rich membrane protrusions [11].

Analytical, diagnostic and therapeutic context of Kcnk2


  1. TREK-1, a K+ channel involved in neuroprotection and general anesthesia. Heurteaux, C., Guy, N., Laigle, C., Blondeau, N., Duprat, F., Mazzuca, M., Lang-Lazdunski, L., Widmann, C., Zanzouri, M., Romey, G., Lazdunski, M. EMBO J. (2004) [Pubmed]
  2. A phospholipid sensor controls mechanogating of the K+ channel TREK-1. Chemin, J., Patel, A.J., Duprat, F., Lauritzen, I., Lazdunski, M., Honoré, E. EMBO J. (2005) [Pubmed]
  3. Localization of TREK-1, a two-pore-domain K+ channel in the peripheral vestibular system of mouse and rat. Nicolas, M.T., Lesage, F., Reyes, R., Barhanin, J., Demêmes, D. Brain Res. (2004) [Pubmed]
  4. 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]
  5. TREK-1, a K+ channel involved in polymodal pain perception. Alloui, A., Zimmermann, K., Mamet, J., Duprat, F., Noël, J., Chemin, J., Guy, N., Blondeau, N., Voilley, N., Rubat-Coudert, C., Borsotto, M., Romey, G., Heurteaux, C., Reeh, P., Eschalier, A., Lazdunski, M. EMBO J. (2006) [Pubmed]
  6. Cloning and functional expression of a novel cardiac two-pore background K+ channel (cTBAK-1). Kim, D., Fujita, A., Horio, Y., Kurachi, Y. Circ. Res. (1998) [Pubmed]
  7. Antipsychotics inhibit TREK but not TRAAK channels. Thümmler, S., Duprat, F., Lazdunski, M. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  8. TREK-1 is a heat-activated background K(+) channel. Maingret, F., Lauritzen, I., Patel, A.J., Heurteaux, C., Reyes, R., Lesage, F., Lazdunski, M., Honoré, E. EMBO J. (2000) [Pubmed]
  9. A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. Fink, M., Lesage, F., Duprat, F., Heurteaux, C., Reyes, R., Fosset, M., Lazdunski, M. EMBO J. (1998) [Pubmed]
  10. TREK-1 regulation by nitric oxide and cGMP-dependent protein kinase. An essential role in smooth muscle inhibitory neurotransmission. Koh, S.D., Monaghan, K., Sergeant, G.P., Ro, S., Walker, R.L., Sanders, K.M., Horowitz, B. J. Biol. Chem. (2001) [Pubmed]
  11. Cross-talk between the mechano-gated K2P channel TREK-1 and the actin cytoskeleton. Lauritzen, I., Chemin, J., Honoré, E., Jodar, M., Guy, N., Lazdunski, M., Jane Patel, A. EMBO Rep. (2005) [Pubmed]
  12. Polyunsaturated fatty acids are potent neuroprotectors. Lauritzen, I., Blondeau, N., Heurteaux, C., Widmann, C., Romey, G., Lazdunski, M. EMBO J. (2000) [Pubmed]
  13. An intracellular proton sensor commands lipid- and mechano-gating of the K(+) channel TREK-1. Honoré, E., Maingret, F., Lazdunski, M., Patel, A.J. EMBO J. (2002) [Pubmed]
  14. Acid-sensitive two-pore domain potassium (K2P) channels in mouse taste buds. Richter, T.A., Dvoryanchikov, G.A., Chaudhari, N., Roper, S.D. J. Neurophysiol. (2004) [Pubmed]
  15. Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Heurteaux, C., Lucas, G., Guy, N., El Yacoubi, M., Thümmler, S., Peng, X.D., Noble, F., Blondeau, N., Widmann, C., Borsotto, M., Gobbi, G., Vaugeois, J.M., Debonnel, G., Lazdunski, M. Nat. Neurosci. (2006) [Pubmed]
  16. Altered acetylcholine, bradykinin and cutaneous pressure-induced vasodilation in mice lacking the TREK1 potassium channel: the endothelial link. Garry, A., Fromy, B., Blondeau, N., Henrion, D., Brau, F., Gounon, P., Guy, N., Heurteaux, C., Lazdunski, M., Saumet, J.L. EMBO Rep. (2007) [Pubmed]
  17. Simultaneous activation of p38 MAPK and p42/44 MAPK by ATP stimulates the K+ current ITREK in cardiomyocytes. Aimond, F., Rauzier, J.M., Bony, C., Vassort, G. J. Biol. Chem. (2000) [Pubmed]
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