An Intracellular Proton Sensor Commands Lipid- and Mechano-gating of the K(+) Channel TREK-1

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2002 Jun 18

PMID 12065410

Citations 98

Authors

Eric Honore

Francois Maingret

Michel Lazdunski

Amanda Jane Patel

Affiliations

Soon will be listed here.

Abstract

The 2P domain K(+) channel TREK-1 is widely expres sed in the nervous system. It is opened by a variety of physical and chemical stimuli including membrane stretch, intracellular acidosis and polyunsaturated fatty acids. This activation can be reversed by PKA-mediated phosphorylation. The C-terminal domain of TREK-1 is critical for its polymodal function. We demonstrate that the conversion of a specific glutamate residue (E306) to an alanine in this region locks TREK-1 in the open configuration and abolishes the cAMP/PKA down-modulation. The E306A substitution mimics intracellular acidosis and rescues both lipid- and mechano-sensitivity of a loss-of-function truncated TREK-1 mutant. We conclude that protonation of E306 tunes the TREK-1 mechanical setpoint and thus sets lipid sensitivity.

Citing Articles

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