Tributyltin-induced Ca2+ mobilization via L-type voltage-dependent Ca2+ channels in PC12 cells

The effects of tributyltin (TBT) on cytosolic Ca2+ concentration ([Ca2+]c) and cell viability were investigated in nerve growth factor-differentiated PC12 cells. TBT concentration dependently increased [Ca2+]c with an EC50 value of 0.07 μM. This effect was markedly reduced by removal of the extracellular Ca2+ or membrane depolarization with a high K+ medium, but unaffected by thapsigargin causing depletion of intracellular Ca2+ stores. The L-type voltage-dependent Ca2+ channel (VDCC) blocker nicardipine blocked the effect of TBT, but the N-type VDCC blocker ω-conotoxin did not. TBT decreased the number of viable cells with an EC50 value of 0.09 μM. The TBT-induced cell death was prevented by nicardipine or by chelating the cytosolic Ca2+ with BAPTA-AM, but not by ω-conotoxin. The results show that TBT causes an increase in [Ca2+]c via activating L-type VDCCs, and support the idea that the organotin-induced cell death arises through Ca2+ mobilization via L-type VDCCs.