Separate Gating Mechanisms Mediate the Regulation of K2P Potassium Channel TASK-2 by Intra- and Extracellular pH

• DOI: 10.1074/jbc.m110.107060
• Publication Date: 2010-03-30T02:24:30Z
• Authors: María Isabel Niem...; L. Pablo Cid; Gaspar Peña-Münze...; Francisco V. Sepú...
• Keywords: Intracellular pH

TASK-2 (KCNK5 or K2P5.1) is a background K+ channel that opened by extracellular alkalinization and plays role in renal bicarbonate reabsorption central chemoreception. Here, we demonstrate addition to its regulation protons (pHo) gated open intracellular alkalinization. The following pieces of evidence suggest the gating process controlled pH (pHi) independent from under command pHo. It was not possible overcome closure acidification means mutant TASK-2-R224A lacks sensitivity pHo had normal pHi-dependent gating. Increasing concentration acid shifts activity curve yet did affect pHi TASK-2. modulation voltage-dependent, whereas altered membrane potential. These results pHo, which controls selectivity filter external gate, act at different processes close channels. We speculate regulates an inner gate. neutralization lysine residue (Lys245) located C-terminal end transmembrane domain 4 mutation alanine abolishes pHi. postulate this acts as sensor histidine acid-shifts pHi-dependence expected lower pKa. conclude pH, together with critical determinant therefore physiological function.