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

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.