Triphenyltin-Induced Increase in the Intracellular Ca²⁺ of Dissociated Mammalian CNS Neuron: Its Independence from Voltage-Dependent Ca²⁺ Channels

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To test the possibility that triphenyltin (TPT) increases the intracellular Ca²⁺ ([Ca²⁺]_i) in neurons as found previously in thymocytes, the effect of TPT on [Ca²⁺]_i was examined in rat cerebellar neurons by a flow-cytometer with fluorescent dyes. TPT at concentrations ranging from 3 × 10^-7 M to 1 × 10^-5 M dose-depend ently increased the [Ca²⁺]_i. The TPT-induced increase in [Ca²⁺]_i was not attenuated by a Ca²⁺ channel blocker, suggesting that it was not dependent on voltage-dependent Ca²⁺ channels. As the concentration of external Ca²⁺ ([Ca²⁺]_e) increased, TPT produced a more profound increase in the [Ca²⁺]_i. However, the increase in the [Ca²⁺]_i by TPT was observed even in nominally [Ca²⁺]_e-free solution. These results suggest two possibilities. First, TPT may promote Ca²⁺-influx to the neuron. Secondly, TPT may affect the intracellular Ca-store sites. This study is relevant to the neurotoxicity of organotins because it has become progressively clear that sustained increases in the [Ca²⁺]_i can activate various Ca²⁺-dependent degradative processes.