Arsenical exposure can cause defects in the central nervous system, yet the underlying cellular and mo-lecular mechanisms are largely unknown. We have recently demonstrated that sodium arsenite induces apoptosis of cultured cortical and cerebellar neurons, suggesting that arsenite-induced neuronal apoptosis may contribute to at least some of its neurotoxic ef-fects. Here we investigated the effect of Ca2+ on ar-senite-mediated cerebellar granule neuron death. So-dium arsenite induced apoptosis in cerebellar neurons which were maintained in the presence of serum and depolarizing concentrations of potassium chloride (25 mM KCl). Under these conditions, inhibition of cal-cium entry by N-methyl-D-aspartate (NMDA) receptor blocker DL-aminophosphonovalerate (APV) or cal-cium channel antagonist nifedipine increased arsenite-induced apoptosis, while APV or nifedipine alone had little effect on cell viability. In cortical neurons or cerebellar neurons maintained at low potassium (5 mM), arsenite also induced apoptosis. However, the addition of APV or nifedipine did not alter levels of arsenite-induced apoptosis. These data suggest that arsenite-mediated apoptosis is regulated by intracellu-lar calcium levels.

Keywords: Cerebellar Neurons, NMDA Receptor, Calcium Channel, Sodium Arsenite, Apoptosis, Calcium