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Gene Review

Kcnk4  -  potassium channel, subfamily K, member 4

Mus musculus

Synonyms: MLZ-622, Potassium channel subfamily K member 4, TRAAK, TRAAKt, TWIK-related arachidonic acid-stimulated potassium channel protein, ...
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Disease relevance of Kcnk4

  • These TRAAK channels might be essential in normal physiological processes in which AA is known to play an important role, such as synaptic transmission, and also in pathophysiological processes such as brain ischemia [1].
  • We investigated here the effects of alpha-linolenic acid and riluzole, both activators of the 2P-domain K+ channel family TREK/TRAAK, in a model of focal ischemia clinically relevant to stroke, not only assessing neuronal protection, but also long term survival [2].
  • In the retina, the TRAAK protein is concentrated to the soma of ganglion cells and to the dendrites of all other neurons [3].

High impact information on Kcnk4


Chemical compound and disease context of Kcnk4


Biological context of Kcnk4

  • Assignment of mouse cardiac two-pore background K+ channel gene (Kcnk4) to the proximal region of mouse chromosome 5 [6].
  • The inactivation of the TREK-1 but not the TRAAK channel in mice results in a depression-resistant phenotype [7].

Anatomical context of Kcnk4

  • 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 [1].
  • Using RT-PCR, the mRNA for TREK-1, but not for TREK-2 or TRAAK, were detected in mouse vestibular endorgans and ganglia [8].
  • TREK-1 was highest in the striatum and in parts of the cortex (layer IV) and hippocampus (CA2 pyramidal neurons). mRNA for TRAAK also was highest in the cortex, whereas expression of TREK-2 was primarily restricted to the cerebellar granule cell layer [9].
  • The most striking finding is the widespread distribution of the TRAAK immunoreactivity, with a prominent staining of the cerebellar cortex, neocortex, hippocampus, dentate gyrus, subiculum, the dorsal hippocampal commissure, thalamus, caudate-putamen, olfactory bulb, and several nuclei in the brainstem [3].

Associations of Kcnk4 with chemical compounds

  • Palmitic acid, a saturated fatty acid that does not activate the 2P-domain K-channel TREK/TRAAK family, did not provide any neuroprotection [2].
  • TRAAK produces baseline K+ currents which are strongly stimulated by arachidonic acid and by mechanical stretch, and which are insensitive to the classical K+ channel blockers tetraethylammonium, Ba2+, and Cs+ [3].

Other interactions of Kcnk4

  • This study shows that the novel subfamily of mechano-gated K2P channels comprising TREK-1, TREK-2, and TRAAK is strongly activated by intracellular LPA [10].
  • We have screened murine gastrointestinal, vascular, bladder, and uterine smooth muscles for the expression of TREK and TRAAK mRNA [5].


  1. 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]
  2. Alpha-linolenic acid and riluzole treatment confer cerebral protection and improve survival after focal brain ischemia. Heurteaux, C., Laigle, C., Blondeau, N., Jarretou, G., Lazdunski, M. Neuroscience (2006) [Pubmed]
  3. Immunolocalization of the arachidonic acid and mechanosensitive baseline traak potassium channel in the nervous system. Reyes, R., Lauritzen, I., Lesage, F., Ettaiche, M., Fosset, M., Lazdunski, M. Neuroscience (2000) [Pubmed]
  4. Polyunsaturated fatty acids are potent neuroprotectors. Lauritzen, I., Blondeau, N., Heurteaux, C., Widmann, C., Romey, G., Lazdunski, M. EMBO J. (2000) [Pubmed]
  5. 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]
  6. Assignment of mouse cardiac two-pore background K+ channel gene (Kcnk4) to the proximal region of mouse chromosome 5. Fujita, A., Horio, Y., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Kurachi, Y. Genomics (1998) [Pubmed]
  7. Antipsychotics inhibit TREK but not TRAAK channels. Thümmler, S., Duprat, F., Lazdunski, M. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  8. 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]
  9. Cns distribution of members of the two-pore-domain (KCNK) potassium channel family. Talley, E.M., Solorzano, G., Lei, Q., Kim, D., Bayliss, D.A. J. Neurosci. (2001) [Pubmed]
  10. Lysophosphatidic acid-operated K+ channels. Chemin, J., Patel, A., Duprat, F., Zanzouri, M., Lazdunski, M., Honoré, E. J. Biol. Chem. (2005) [Pubmed]
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