TABLE 4

K2P4.1 channels

Channel name K2P4.1
Description Two-pore domain potassium channel subunit; open rectifier
Other names KCNK4, TRAAK
Molecular information Human: 393aa, NM_016611, chr. 11q13, KCNK4,1 GeneID: 50801, PMID: 107674091
Rat: 397aa, NM_053804, kcnk4
Mouse: 398aa, NM_008431, chr. 19, kcnk4
Associated subunits Not established
Functional assays Electrophysiological2
Current Open rectifier
Conductance 46pS
Ion selectivity Not established
Activation See “Comments”
Inactivation See “Comments”
Activators Arachidonic acid (10 mM),3 mechanical stress,4 heat6 (see “Comments”), unsaturated fatty acids,3 lysopholipids,7 riluzole8
Gating inhibitors None
Blockers Gd+
Radioligands None
Channel distribution Brain,5 kidney, small intestine, placenta, prostate
Physiological functions Not established
Mutations and pathophysiology Not established
Pharmacological significance Not established
Comments Activation and deactivation with voltage steps seem to be instantaneous; knockout mice have no obvious phenotype9; the open probability of K2P4 increases with temperature with an activation threshold of 31°C in COS-7 cells
  • aa, amino acids; chr., chromosome.

  • 1. Lesage F, Maingret F, and Lazdunski M (2000) Cloning and expression of human TRAAK, a poly-unsaturated fatty acids-activated and mechano-sensitive K(+) channel. FEBS Lett 471:137-140

  • 2. Kim Y, Bang H, Gnatenco C, and Kim D (2001) Synergistic interaction and the role of C-terminus in the activation of TRAAK K+ channels by pressure, free fatty acids and alkali. Pflueg Arch Eur J Physiol 442:64-72

  • 3. Fink M, Lesage F, Duprat F, Heurteaux C, Reyes R, Fosset M, and Lazdunski M (1998) A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. EMBO J 17:3297-3308

  • 4. Maingret F, Fosset M, Lesage F, Lazdunski M, and Honoré E (1999) TRAAK is a mammalian neuronal mechanogated K+ channel. J Biol Chem 274:1381-1387

  • 5. Reyes R, Lauritzen I, Lesage F, Ettaiche M, Fosset M, and Lazdunski M (2000) Immunolocalization of the arachidonic acid and mechanosensitive baseline traak potassium channel in the nervous system. Neuroscience 95:893-901

  • 6. Kang DW, Choe CY, and Kim D (2005) Thermosensitivity of the two-pore domain K+ channels TREK-2 and TRAAK. J Physiol 564.1:103-116

  • 7. Maingret F, Patel AJ, Lesage F, Lazdunski M, and Honoré E (2000) Lysophospholipids open the two-pore domain mechano-gated K(+) channels TREK-1 and TRAAK. J Biol Chem 275:10128-10133

  • 8. Duprat F, Lesage F, Patel AJ, Fink M, Romey G, and Lazdunski M (2000) The neuroprotective agent riluzole activates the two P domain K + channels TREK-1 and TRAAK. Mol Pharmacol 57:906-912

  • 9. Heurteaux C, Guy N, Laigle C, Blondeau N, Duprat F, Mazzuca M, Lang-Lazdunski L, Widmann C, Zanzouri M, Romey G, et al. (2004) TREK-1, a K+ channel involved in neuroprotection and general anesthesia. EMBO J 23:2684-2695