Article
- The EMBO Journal (2005) 24, 44 - 53
- doi:10.1038/sj.emboj.7600494
Published online: 2 December 2004
Subject Categories:
A phospholipid sensor controls mechanogating of the K+ channel TREK-1
Jean Chemin1,a, Amanda Jane Patel1,a, Fabrice Duprat1, Inger Lauritzen1, Michel Lazdunski1 and Eric Honoré1
- Institut de Pharmacologie, Moléculaire et Cellulaire, Institut Paul Hamel, Sophia Antipolis, Valbonne, France
Correspondence to:
Eric Honoré, Institut de Pharmacologie, Moléculaire et Cellulaire, CNRS-UMR 6097, Institut Paul Hamel, 660, Route des Lucioles, Sophia Antipolis, 06560 Valbonne, France. Tel.: +33 493 957702/03; Fax: +33 493 957704; E-mail: honore@ipmc.cnrs.fr
aThese authors contributed equally to this work
Received 30 August 2004; Accepted 4 November 2004
Abstract
TREK-1 (KCNK2 or K2P2.1) is a mechanosensitive K2P channel that is opened by membrane stretch as well as cell swelling. Here, we demonstrate that membrane phospholipids, including PIP2, 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-, pHi- and voltage-dependent gating.
Keywords:
- general anesthesia,
- KCNK,
- K2P,
- neuro-protection,
- stretch
