L-type Ca2+ channels and SK channels in mouse embryonic stem cells and their contribution to cell proliferation

Abstract

Mouse embryonic stem cells (mESCs) are capable of both self-renewal and multilineage differentiation; thus, they can be expanded in vivo or in vitro and differentiated to produce different cell types. Despite their biological and medical interest, many physiological properties of undifferentiated mESCs, such as ion channel function, are not fully understood. Ion channels are thought to be involved in cell proliferation and differentiation. The aim of this study was to characterize functional ion channels in cultured undifferentiated mESCs and their role in cell proliferation. L-type voltage-activated Ca2+ channels sensitive to nifedipine and small conductance Ca2+- activated K+ (SK) channels sensitive to apamin were identified. Ca2+-activated K+ currents were blocked by millimolar concentrations of tetraethylammonium (TEA). The effects of Ca2+ channel and Ca2+-activated K+ channel blockers on the proliferation of undifferentiated mESCs were investigated by bromodeoxyuridine (BrdU) incorporation. Dihydropyridine derivatives, such as nifedipine, inhibited cell growth and BrdU incorporation into the cells, whereas apamin, which selectively blocks SK channels, had no effect on cell growth. These results demonstrate that functional voltageoperated Ca2+ channels (VOCCs) and Ca2+-activated K+ channels are present in undifferentiated mESCs. Moreover, voltage-gated L-type Ca2+ channels, but not SK channels, might be necessary for proliferation of undifferentiated mESCs.