Chronic exposure to inorganic lead increases high-threshold voltage-gated calcium currents in rat pheochromocytoma (PC12) cells

Rat pheochromocytoma (PC12) cells were exposed to lead acetate (0, 10, 25 and 50 microM) in their growth media for up to 12 weeks. High-threshold voltage-gated calcium currents were recorded each week from nerve growth factor-differentiated PC12 cells using the whole-cell patch-clamp technique. Chronic exposure for 1 month did not modify peak or sustained calcium current amplitudes in lead-treated cells when compared to sister control cultures. Two month exposure to 25 and 50 microM significantly increased peak and sustained calcium current amplitudes, while 10 microM had little effect. During the third month of exposure, peak and sustained calcium current amplitudes remained increased in the cells exposed to 25 and 50 microM lead acetate. By the end of the second month of exposure to 25 and 50 microM lead acetate, the voltage at which maximal current amplitude was attained shifted from + 10 mV to 0 mV. The observed effects of toxicologically relevant lead concentrations on high-threshold calcium currents in chronically exposed mammalian cells provide further support for the notion that at least one cellular target of the heavy metal's neurotoxic action may be the voltage-gated calcium channel.