Extracellular acidification exerts opposite actions on TREK1 and TREK2 potassium channels via a single conserved histidine residue.

ABSTRACT: Mechanosensitive K(+) channels TREK1 and TREK2 form a subclass of two P-domain K(+) channels. They are potently activated by polyunsaturated fatty acids and are involved in neuroprotection, anesthesia, and pain perception. Here, we show that acidification of the extracellular medium strongly inhibits TREK1 with an apparent pK near to 7.4 corresponding to the physiological pH. The all-or-none effect of pH variation is steep and is observed within one pH unit. TREK2 is not inhibited but activated by acidification within the same range of pH, despite its close homology with TREK1. A single conserved residue, H126 in TREK1 and H151 in TREK2, is involved in proton sensing. This histidine is located in the M1P1 extracellular loop preceding the first P domain. The differential effect of acidifica

SUBMITTER: Sandoz G 

PROVIDER: S-EPMC2732798 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature