Chemin Jean, Patel Amanda Jane, Duprat Fabrice, Lauritzen Inger, Lazdunski Michel, Honoré Eric
Institut de Pharmacologie, Moléculaire et Cellulaire, Institut Paul Hamel, Sophia Antipolis, Valbonne, France.
EMBO J. 2005 Jan 12;24(1):44-53. doi: 10.1038/sj.emboj.7600494. Epub 2004 Dec 2.
TREK-1 (KCNK2 or K(2P)2.1) is a mechanosensitive K(2P) channel that is opened by membrane stretch as well as cell swelling. Here, we demonstrate that membrane phospholipids, including PIP(2), control channel gating and transform TREK-1 into a leak K(+) conductance. A carboxy-terminal positively charged cluster is the phospholipid-sensing domain that interacts with the plasma membrane. This region also encompasses the proton sensor E306 that is required for activation of TREK-1 by cytosolic acidosis. Protonation of E306 drastically tightens channel-phospholipid interaction and leads to TREK-1 opening at atmospheric pressure. The TREK-1-phospholipid interaction is critical for channel mechano-, pH(i)- and voltage-dependent gating.
TREK-1（KCNK2或K(2P)2.1）是一种机械敏感的K(2P)通道，可通过膜拉伸以及细胞肿胀而开放。在此，我们证明包括磷脂酰肌醇-4,5-二磷酸（PIP(2)）在内的膜磷脂可控制通道门控，并将TREK-1转变为一种泄漏钾离子（K(+)）电导。一个羧基末端带正电荷的簇是与质膜相互作用的磷脂传感结构域。该区域还包含质子传感器E306，胞质酸中毒激活TREK-1需要该传感器。E306的质子化极大地增强了通道与磷脂的相互作用，并导致TREK-1在常压下开放。TREK-1与磷脂的相互作用对于通道的机械、细胞内pH（pH(i)）和电压依赖性门控至关重要。
