TABLE 2

K2P2.1 channels

Channel name K2P2.1
Description Two-pore domain potassium channel subunit1; open rectifier or voltage-dependent
Other names KCNK2, TREK-1, TPKC1
Molecular information Human: 426aa, NM_014217, chr. 1q41, KCNK2,2 GeneID: 3776, PMID: 90037613
Rat: 426aa, AF325671, chr. 5
Mouse: 411aa, XM_123605, chr. 1, kcnk23
Associated subunits Not established
Functional assays Electrophysiological
Current Open or voltage-dependent4,5 (see “Comments”)
Conductance 90pS (see “Comments”)
Ion selectivity Not established
Activation See “Comments”
Inactivation See “Comments”
Activators Arachidonic acid (10 mM) and unsaturated fatty acids,10 lysophospholipids,7 volatile anesthetics,6,11 mechanical stress,7,11 internal acidification12
Gating inhibitors None
Blockers Ba2+ (1 mM), quinidine (100 mM), PKA, PKC
Radioligands None
Channel distribution Brain,2 heart
Physiological functions Not established
Mutations and pathophysiology Characterization of K2P2 knockout mice suggests a loss of sensitivity to general anesthetics and increased vulnerability to ischemia and reperfusion injury8,9
Pharmacological significance Not established
Comments Phosphorylation of serine 348 regulates reversible interconversion between leak and voltage-dependent phenotypes5; “activation” and “deactivation” with voltage steps seem to be instantaneous; the mouse variant may have a smaller conductance

  • aa, amino acids; chr., chromosome; PKA, protein kinase A; PKC, protein kinase C.

  • ↵1. Goldstein SAN, Wang KW, Ilan N, and Pausch M (1998) Sequence and function of the two P domain potassium channels: implications of an emerging superfamily. J Mol Med 76:13-20

  • ↵2. Meadows HJ, Benham CD, Cairns W, Gloger I, Jennings C, Medhurst AD, Murdock P, and Chapman CG (2000) Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel. Pflueg Arch Eur J Physiol 439:714-722

  • ↵3. Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, and Lazdunski M (1996) Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. EMBO J 15:6854-6862

  • ↵4. Maingret F, Lauritzen I, Patel AJ, Heurteaux C, Reyes R, Lesage F, Lazdunski M, and Honoré E (2000) TREK-1 is a heat-activated background K(+) channel. EMBO J 19:2483-2491

  • ↵5. Bockenhauer D, Zilberberg N, and Goldstein SAN (2001) KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel. Nat Neurosci 4:486-491

  • ↵6. Terrenoire C, Lauritzen I, Lesage F, Romey G, and Lazdunski M (2001) A TREK-1-like potassium channel in atrial cells inhibited by beta-adrenergic stimulation and activated by volatile anesthetics. Circ Res 89:336-342

  • ↵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. Buckler KJ and Honoré E (2004) The lipid-activated K2P channel TREK-1 is resistant to hypoxia: implication for ischemic neuroprotection. J Physiol 562:213-222

  • ↵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

  • ↵10. Patel AJ, Honoré E, Lesage F, Fink M, Romey G, and Lazdunski M (1999) Inhalational anesthetics activate two-pore-domain background K+ channels. Nat Neurosci 2:422-426

  • ↵11. Maingret F, Patel AJ, Lesage F, Lazdunski M, and Honoré E (1999) Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J Biol Chem 274:26691-26696