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 concentrationdependent 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 Ca2 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.