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EFFECTS OF SUBSCUTE EXPOSURE TO NANOMOLAR CONCENTRATIONS OF METHYLMERCURY ON VOLTAGE-GATES SODIUM AND CALCIUM CURRENTS IN PC12 CELLS.
Citation:
Shafer, T J. AND C A. Meacham. EFFECTS OF SUBSCUTE EXPOSURE TO NANOMOLAR CONCENTRATIONS OF METHYLMERCURY ON VOLTAGE-GATES SODIUM AND CALCIUM CURRENTS IN PC12 CELLS. Presented at 18th International Neurotoxicology Conference, Colorado Springs, CO, 9/23-26, 2000.
Description:
Methylmercury (CH3Hg+) alters the function of voltage-gated Na+ and Ca2+ channels in neuronal preparations following acute, in vitro, exposure. Because the developing nervous system is particularly sensitive to CH3Hg+ neurotoxicity, effects on voltage-gated Na+ (INa) and Ca2+ (ICa) currents in pheochromocytoma (PC12) cells were examined following subacute exposure to nanomolar concentrations of CH3Hg+. PC12 cells were cultured in the presence of nerve growth factor (NGF) for 7 days and then replated in the presence of NGF and 30 nM CH3Hg+. The amplitude and density of ICa were significantly reduced when recorded approximately 24 Hr later; at a test potential of +20 mV, ICa was reduced by 29% in cells treated with CH3Hg+ when compared to control cells. However, there was no effect of this single subacute treatment on INa. By contrast, when undifferentiated PC12 cells were cultured in the presence of NGF and 10 nM CH3Hg+ for 6 days, the amplitude and density of ICa and ICa were significantly reduced in the absence of cytotoxicity. Cells treated for 6 days with 10 nM CH3Hg+ had peak ICa and INa which were 36 and 52 % smaller than control ICa and INa, respectively. Ca2+ current at the end of the 150 ms test pulse was also reduced by approximately 40% in CH3Hg+-treated cells. Thus, both inactivating and non-inactivating current in PC12 cells were equally reduced by the CH3Hg+ treatment. For comparison, culture of PC12 cells in the presence of NGF and the N-type voltage-sensitive Ca2+ channel blocker -conotoxin GVIA (500 pM) for 6 days, significantly reduced ICa, but not INa. These results demonstrate that low concentrations of CH3Hg+ reduce cationic currents in differentiating PC12 cells. Such effects may be involved mechanisms underlying the developmental neurotoxicity of CH3Hg+.(This abstract does not reflect EPA policy).