Expression of Different Subunits of the Calcium-Regulated BK Channel in Rat Brain and Its Putative Cytoprotective Properties

Abstract

BKCa is ubiquitously expressed in the plasma membrane of both excitable and non-excitable cells. Although it was extensively studied mainly in plasma membrane, its counterpart exists also in mitochondria (mitoBKCa). It was identified in mitochondria of several cell types including astrocytes and neurons.Potassium channels are notorious for their role in cytoprotection but the mechanisms of these properties remain to be elucidated. However, it is suspected that attenuation of ROS generation and mild uncoupling in mitochondria occurring upon activation of the mitoBKCa may play some role in this phenomenon.In the current study we have evaluated the expression pattern of different subunits of the BKCa channel within certain areas of rat brain. We could show that there is a correlation between the mtDNA copy number and the expression level of the BKCa β4 auxiliary subunit. The expression of the β1, β2 and β3 subunits in different brain areas does not seem to correlate with the mtDNA copy number.This strongly suggest that β4 auxiliary subunit might be a constituent of mitoBKCa in rat brain. This finding supports the recent report about the expression of this subunit in the astrocytoma U-87 MG cell line1.The presence of the mitoBKCa in brain can explain why NS-1619 (a BKCa opener) inhibits ROS generation rate and causes mild dissipation of the membrane potential in succinate energized rat brain mitochondria.1. Bednarczyk, P. et al. Putative Structural and Functional Coupling of the Mitochondrial BKCa Channel to the Respiratory Chain. PloS one8, e68125 (2013).This study is supported by the International PhD Program in Neurobiology coordinated by The Foundation for Polish Science and financed from the European Funds.