Regulation of inward rectifier K+ channels by shift of intracellular pH dependence

Journal of Cellular Physiology
Anthony Collins, Maureen K Larson

Abstract

The mechanistic link between mitochondrial metabolism and inward rectifier K+ channel activity was investigated by studying the effects of a mitochondrial inhibitor, carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) on inward rectifiers of the Kir2 subfamily expressed in Xenopus oocytes, using two-electrode voltage-clamp, patch-clamp, and intracellular pH recording. FCCP inhibited Kir2.2 and Kir2.3 currents and decreased intracellular pH, but the pH change was too small to account for the inhibitory effect by itself. However, pre-incubation of oocytes with imidazole prevented both the pH decrease and the inhibition of Kir2.2 and Kir2.3 currents by FCCP. The pH dependence of Kir2.2 was shifted to higher pH in membrane patches from FCCP-treated oocytes compared to control oocytes. Therefore, the inhibition of Kir2.2 by FCCP may involve a combination of intracellular acidification and a shift in the intracellular pH dependence of these channels. To investigate the sensitivity of heteromeric channels to FCCP, we studied its effect on currents expressed by heteromeric tandem dimer constructs. While Kir2.1 homomeric channels were insensitive to FCCP, both Kir2.1-Kir2.2 and Kir2.1-Kir2.3 heterotetrameric channels were inhibite...Continue Reading

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Citations

Oct 6, 2009·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Joseph R McDermottZijuan Liu
Apr 3, 2007·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Martin B Rook
Jun 23, 2010·Journal of Cellular Physiology·Dana GoldoniAnthony Collins
Jul 13, 2016·The Journal of Biological Chemistry·Ming-Hua LiZhi-Gang Xiong

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