期刊
EMBO JOURNAL
卷 21, 期 12, 页码 2968-2976出版社
WILEY
DOI: 10.1093/emboj/cdf288
关键词
acidosis; arachidonic acid; KCNK2; phosphorylation; 2P domain K+ channels
The 2P domain K+ channel TREK-1 is widely expressed 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.
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