Mitochondrial BK(Ca) channel

Since its discovery in a glioma cell line 15 years ago, mitochondrial BK(Ca) channel (mitoBK(Ca)) has been studied in brain cells and cardiomyocytes sharing general biophysical properties such as high K(+) conductance (~300 pS), voltage-dependency and Ca(2+)-sensitivity. Main advances in deciphering the molecular composition of mitoBK(Ca) have included establishing that it is encoded by the Kcnma1 gene, that a C-terminal splice insert confers mitoBK(Ca) ability 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 mitoBK(Ca) can be modulated by substrates of the respiratory chain. mitoBK(Ca) channel 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 Ca(2+) preventing cell death likely by impeding uncontrolled opening of the mitochondrial transition pore. Supporting this view, inhibition of mitoBK(Ca) with Iberiotoxin, enhances cytochrome c release from glioma mitochondria. Many tantalizing questions remain open. Some of them are: how is mitoBK(Ca) coupled to the respiratory chain? Does mitoBK(Ca) play non-conduction roles in mitochondria physiology? Which are the functional partners of mitoBK(Ca)? What are the roles of mitoBK(Ca) in other cell types? Answers to these questions are essential to define the impact of mitoBK(Ca) channel in mitochondria biology and disease.