Increase in cytosolic Ca2+ induced by elevation of extracellular Ca2+ in skeletal myogenic cells

Cytoplasmic Ca2+ concentration ([Ca2+](i)) variation is a key event in myoblast differentiation, but the mechanism by which it occurs is still debated. Here we show that increases of extracellular Ca2+ concentration ([Ca2+](o)) produced membrane hyperpolarization and a concentration-dependent increase of [Ca2+](i) due to Ca2+ influx across the plasma membrane. Responses were not related to inositol phosphate turnover and Ca2+-sensing receptor. [Ca2+](o)-induced [Ca2+](i) increase was inhibited by Ca(2+)channel inhibitors and appeared to be modulated by several kinase activities. [Ca2+](i) increase was potentiated by depletion of intracellular Ca2+ stores and depressed by inactivation of the Na+/Ca2+ exchanger. The response to arginine vasopressin (AVP), which induces inositol 1,4,5-trisphosphate-dependent [Ca2+](i) increase in L6-C5 cells, was not modified by high [Ca2+](o). On the contrary, AVP potentiated the [Ca2+](i) increase in the presence of elevated [Ca2+](o). Other clones of the L6 line as well as the rhabdomyosarcoma RD cell line and the satellite cell-derived C2-C12 line expressed similar responses to high [Ca2+](o), and the amplitude of the responses was correlated with the myogenic potential of the cells.