Maingret F, Patel A J, Lesage F, Lazdunski M, Honoré E
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
J Biol Chem. 1999 Sep 17;274(38):26691-6. doi: 10.1074/jbc.274.38.26691.
TREK-1 is a member of the novel structural class of K(+) channels with four transmembrane segments and two pore domains in tandem (1,2). TREK-1 is opened by membrane stretch and arachidonic acid. It is also an important target for volatile anesthetics (2,3). Here we show that internal acidification opens TREK-1. Indeed, lowering pH(i) shifts the pressure-activation relationship toward positive values and leads to channel opening at atmospheric pressure. The pH(i)-sensitive region in the carboxyl terminus of TREK-1 is the same that is critically involved in mechano-gating as well as arachidonic acid activation. A convergence, which is dependent on the carboxyl terminus, occurs between mechanical, fatty acids and acidic stimuli. Intracellular acidosis, which occurs during brain and heart ischemia, will induce TREK-1 opening with subsequent K(+) efflux and hyperpolarization.
TREK-1是一种新型结构类钾通道的成员，具有四个跨膜片段和两个串联的孔结构域（1,2）。TREK-1可被膜拉伸和花生四烯酸激活。它也是挥发性麻醉剂的重要靶点（2,3）。在此我们表明，细胞内酸化可打开TREK-1。实际上，降低细胞内pH值会使压力激活关系向正值偏移，并导致通道在大气压下开放。TREK-1羧基末端的pH敏感区域与机械门控以及花生四烯酸激活密切相关的区域相同。在机械、脂肪酸和酸性刺激之间存在一种依赖于羧基末端的汇聚现象。在脑和心脏缺血期间发生的细胞内酸中毒，将诱导TREK-1开放，随后钾离子外流和超极化。
