Mitochondrial BKCa channel

Abstract

Since its discovery in a glioma cell line 15 years ago, mitochondrial BKCachannel (mitoBKCa) has been studied in brain cells and cardiomyocytes sharing general biophysical properties such as high K+conductance (~300 pS), voltage-dependency and Ca2+-sensitivity. Main advances in deciphering the molecular composition of mitoBKCahave included establishing that it is encoded by the Kcnma1 gene, that a C-terminal splice insert confers mitoBKCaability to be targeted to cardiac mitochondria, and evidence for its potential coassembly with Β subunits. Notoriously, Β1 subunit directly interacts with cytochrome c oxidase and mitoBKCacan be modulated by substrates of the respiratory chain. mito BKCachannel has a central role in protecting the heart from ischemia, where pharmacological activation of the channel impacts the generation of reactive oxygen species and mitochondrial Ca2+preventing cell death likely by impeding uncontrolled opening of the mitochondrial transition pore. Supporting this view, inhibition of mito BKCawith Iberiotoxin, enhances cytochrome c release from glioma mitochondria. Many tantalizing questions remain open. Some of them are: how is mitoBKCacoupled to the respiratory chain? Does mitoBKCaplay non-conduction roles in mitochondria physiology? Which are the functional partners of mitoBKCa? What are the roles of mitoBKCain other cell types? Answers to these questions are essential to define the impact of mitoBKCachannel in mitochondria biology and disease.