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 mu M) in their growth media for up to 12 weeks. High-thresh old voltage-gated calcium currents were recorded each week from nerve growth factor-differentiated PC12 cells using the whole-cell patch-cla mp technique. Chronic exposure for 1 month did not modify peak or sust ained calcium current amplitudes in lead-treated cells when compared t o sister control cultures. Two month exposure to 25 and 50 mu M signif icantly increased peak and sustained calcium current amplitudes, while 10 mu M had little effect. During the third month of exposure, peak a nd sustained calcium current amplitudes remained increased in the cell s exposed to 25 and 50 mu M lead acetate. By the end of the second mon th of exposure to 25 and 50 mu M lead acetate, the voltage at which ma ximal current amplitude was atrained shifted from +10 mV to 0 mV. The observed effects of toxicologically relevant lead concentrations on hi gh-threshold calcium currents in chronically exposed mammalian cells p rovide further support for the notion that at least one cellular targe t of the heavy metal's neurotoxic action may be the voltage-gated calc ium channel. (C) 1997 Elsevier Science B.V.