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Gene Review

KCNK4  -  potassium channel, two pore domain...

Homo sapiens

Synonyms: K2p4.1, Potassium channel subfamily K member 4, TRAAK, TRAAK1, TWIK-related arachidonic acid-stimulated potassium channel protein, ...
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Disease relevance of KCNK4

  • Opening of TREK-1 and TRAAK by fatty acids and LPs may be an important switch in the regulation of synaptic function and may also play a protective role during ischemia and inflammation [1].

High impact information on KCNK4

  • Reverse transcription-polymerase chain reaction screening indicates that all known channels other than hTWIK1 and hTRAAK are expressed in H146 cells [2].
  • Lysophospholipids open the two-pore domain mechano-gated K(+) channels TREK-1 and TRAAK [1].
  • This report shows that TRAAK, which was known to be activated by arachidonic acid (3), is also opened by membrane stretch [3].
  • Mechanical activation of TRAAK in the central nervous system may play an important role during growth cone motility and neurite elongation [3].
  • Finally, TRAAK is reversibly blocked by micromolar concentrations of gadolinium, a well known blocker of stretch-activated channels [3].

Biological context of KCNK4


Anatomical context of KCNK4

  • Human KCNK4 transcripts were expressed mainly in the heart and brain but also in the liver, skeletal muscle, kidney and pancreas [4].
  • In COS cells, hTRAAK currents are K(+)-selective, instantaneous and non-inactivating [5].
  • Quantitative mRNA expression analysis using Taqman revealed that hTRAAK mRNA is predominantly present in the central nervous system where it exhibits a regionally diverse pattern of expression [6].
  • Unlike its counterparts, TRAAK is only expressed in neuronal tissues, including brain, spinal cord, and retina (1) [3].
  • Mechanical activation of TRAAK is induced by a convex curvature of the plasma membrane and can be mimicked by the amphipathic membrane crenator trinitrophenol [3].

Associations of KCNK4 with chemical compounds


Other interactions of KCNK4

  • Several sub-families of the two pore domain potassium channel family have been described, including the weakly inward rectifying K+ channel (TWIK), the acid-sensitive K+ channel (TASK), the TWIK-related K+ channel (TREK) and the TWIK-related arachidonic acid stimulated K+ channel (TRAAK) [10].
  • TREK-1 and TRAAK mRNA expression was predominantly CNS specific in contrast to the closely related TREK-2, which was expressed in both CNS and peripheral tissues [10].
  • RESULT(S): Molecular analysis demonstrated expression and specific regional distribution of TRAAK, TREK-1, and TASK-2 in nonhuman primate sperm [11].

Analytical, diagnostic and therapeutic context of KCNK4

  • Using RT-PCR and a semiquantitative method to detect relative differences in mRNA expression, we examined uterine smooth muscle from both pregnant and non-pregnant women for the expression of members of weak inwardly rectifying 2-pore potassium channel family (TWIK), TREK and TRAAK [12].


  1. Lysophospholipids open the two-pore domain mechano-gated K(+) channels TREK-1 and TRAAK. Maingret, F., Patel, A.J., Lesage, F., Lazdunski, M., Honoré, E. J. Biol. Chem. (2000) [Pubmed]
  2. Combined antisense and pharmacological approaches implicate hTASK as an airway O(2) sensing K(+) channel. Hartness, M.E., Lewis, A., Searle, G.J., O'Kelly, I., Peers, C., Kemp, P.J. J. Biol. Chem. (2001) [Pubmed]
  3. TRAAK is a mammalian neuronal mechano-gated K+ channel. Maingret, F., Fosset, M., Lesage, F., Lazdunski, M., Honoré, E. J. Biol. Chem. (1999) [Pubmed]
  4. Cloning of two transcripts, HKT4.1a and HKT4.1b, from the human two-pore K+ channel gene KCNK4. Chromosomal localization, tissue distribution and functional expression. Ozaita, A., Vega-Saenz de Miera, E. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  5. Cloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K(+) channel. Lesage, F., Maingret, F., Lazdunski, M. FEBS Lett. (2000) [Pubmed]
  6. The neuroprotective agent sipatrigine (BW619C89) potently inhibits the human tandem pore-domain K(+) channels TREK-1 and TRAAK. Meadows, H.J., Chapman, C.G., Duckworth, D.M., Kelsell, R.E., Murdock, P.R., Nasir, S., Rennie, G., Randall, A.D. Brain Res. (2001) [Pubmed]
  7. Antipsychotics inhibit TREK but not TRAAK channels. Thümmler, S., Duprat, F., Lazdunski, M. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  8. 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]
  9. Trichloroethanol enhances the activity of recombinant human TREK-1 and TRAAK channels. Harinath, S., Sikdar, S.K. Neuropharmacology (2004) [Pubmed]
  10. Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery. Medhurst, A.D., Rennie, G., Chapman, C.G., Meadows, H., Duckworth, M.D., Kelsell, R.E., Gloger, I.I., Pangalos, M.N. Brain Res. Mol. Brain Res. (2001) [Pubmed]
  11. Expression of two-pore domain potassium channels in nonhuman primate sperm. Chow, G.E., Muller, C.H., Curnow, E.C., Hayes, E.S. Fertil. Steril. (2007) [Pubmed]
  12. Expression of stretch-activated potassium channels in human myometrium. Tichenor, J.N., Hansen, E.T., Buxton, I.L. Proc. West. Pharmacol. Soc. (2005) [Pubmed]
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