β-Cell CaVchannel regulation in physiology and pathophysiology

Abstract

The β-cell is equipped with at least six voltage-gated Ca2+(CaV) channel α1-subunits designated CaV1.2, CaV1.3, CaV2.1, CaV2.2, CaV2.3, and CaV3.1. These principal subunits, together with certain auxiliary subunits, assemble into different types of CaVchannels conducting L-, P/Q-, N-, R-, and T-type Ca2+currents, respectively. The β-cell shares customary mechanisms of CaVchannel regulation with other excitable cells, such as protein phosphorylation, Ca2+-dependent inactivation, and G protein modulation. However, the β-cell displays some characteristic features to bring these mechanisms into play. In islet β-cells, CaVchannels can be highly phosphorylated under basal conditions and thus marginally respond to further phosphorylation. In β-cell lines, CaVchannels can be surrounded by tonically activated protein phosphatases dominating over protein kinases; thus their activity is dramatically enhanced by inhibition of protein phosphatases. During the last 10 years, we have revealed some novel mechanisms of β-cell CaVchannel regulation under physiological and pathophysiological conditions, including the involvement of exocytotic proteins, inositol hexakisphosphate, and type 1 diabetic serum. This minireview highlights characteristic features of customary mechanisms of CaVchannel regulation in β-cells and also reviews our studies on newly identified mechanisms of β-cell CaVchannel regulation.