DIMINISHED BLOCKING EFFECT OF ACUTE LEAD-EXPOSURE ON HIGH-THRESHOLD VOLTAGE-GATED CALCIUM CURRENTS IN PC12 CELLS CHRONICALLY EXPOSED TO THEHEAVY-METAL

Rat pheochromocytoma (PC12) cells were grown in 0, 10, 25, or 50 mu M lead-containing growth media for up to twelve weeks. High-threshold wh ole-cell calcium currents from these PC12 cells were recorded in lead- free recording media (control), then in 1 mu M lead-containing recordi ng media (acute challenge), and finally again in lead-free recording m edia (wash). The acute lead challenge decreased calcium currents in al l treatment groups (including 0 mu M lead). However, this blocking eff ect of acute lead application diminished with prolonged chronic exposu re to 25 and 50 mu M lead. Although the acute lead challenge mainly ca used a decrease in calcium currents, in some chronically exposed PC12 cells increased calcium currents were recorded during the application of 1 mu M lead acetate. In other chronically exposed PC12 cells, the a cute lead challenge caused the peak of the current-voltage curve to sh ift from +10 mV to 0 mV The number of cells exhibiting either an incre ase in calcium current or a shift in the current-voltage relationship following acute lead challenge increased with prolonged chronic exposu re to the heavy metal. The time-dependent increase in calcium influx m ay be responsible for at least one manifestation of lead neurotoxicity . (C) 1998 Intox Press, Inc.