Diminished blocking effect of acute lead exposure on high-threshold voltage-gated calcium currents in PC12 cells chronically exposed to the heavy metal.

Rat pheochromocytoma (PC12) cells were grown in 0, 10, 25, or 50 microM lead-containing growth media for up to twelve weeks. High-threshold whole-cell calcium currents from these PC12 cells were recorded in lead-free recording media (control), then in 1 microM lead-containing recording media (acute challenge), and finally again in lead-free recording media (wash). The acute lead challenge decreased calcium currents in all treatment groups (including 0 microM lead). However, this blocking effect of acute lead application diminished with prolonged chronic exposure to 25 and 50 microM lead. Although the acute lead challenge mainly caused a decrease in calcium currents, in some chronically exposed PC12 cells increased calcium currents were recorded during the application of 1 microM lead acetate. In other chronically exposed PC12 cells, the acute lead challenge caused the peak of the current-voltage curve to shift from +10 mV to 0 mV. The number of cells exhibiting either an increase in calcium current or a shift in the current-voltage relationship following acute lead challenge increased with prolonged chronic exposure to the heavy metal. The time-dependent increase in calcium influx may be responsible for at least one manifestation of lead neurotoxicity.