Critical role of L-type voltage-dependent Ca2+ channels in neural progenitor cell proliferation induced by hypoxia

Abstract Hypoxia can promote proliferation of neural progenitor cells in vitro and in vivo , however, the mechanisms underlying this phenomenon remain largely unknown. Calcium ions are important for the proliferation of progenitor cells. In this study, we reported that Ca 2+ influx through L-type voltage-dependent Ca 2+ channels mediated hypoxia-promoted proliferation of neural progenitor cells isolated from embryonic day 14.5 rat mesencephalon. Cell number was greatly increased in the cultured neural progenitor cells exposed to physiological hypoxia (3% O 2 , 72 h) compared with normoxia exposure (20% O 2, 72 h). Increased intracellular Ca 2+ concentration was also observed when the cells were exposed to hypoxia. Moreover, removal of extracellular Ca 2+ or administration of nicardipine, an agent known to block L-type Ca 2+ channels, resulted in suppression of the hypoxia-induced increase in intracellular Ca 2+ and cell numbers. These results suggest that hypoxia promoted the proliferation of neural progenitor cells by increasing Ca 2+ influx, which was likely a result of upregulation of L-type voltage-dependent Ca 2+ channel function.