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PERCHLOROETHYLENE (PERC) INHIBITS FUNCTION OF VOLTAGE-GATED CALCIUM CHANNELS IN PHEOCHROMOCYTOMA CELLS.
Citation:
Shafer, T J. PERCHLOROETHYLENE (PERC) INHIBITS FUNCTION OF VOLTAGE-GATED CALCIUM CHANNELS IN PHEOCHROMOCYTOMA CELLS. Presented at Society of Toxicology 42nd Annual Meeting, Salt Lake City, UT, March 9-13, 2003.
Description:
The industrial solvent perchloroethylene (PERC) is listed as a hazardous air pollutant in the 1990 Ammendments to Clean Air Act and is a known neurotoxicant. However, the mechanisms by which PERC alters nervous system function are poorly understood. In recent years, it has been demonstrated that volatile organic solvents such as toluene and trichloroethylene disrupt the function of ligand and voltage-gated ion channels in neurons, including voltage-gated calcium channels (VGCC). The present experiments examined the hypothesis that PERC also disrupts ion channel function by examining PERC effects on Ca2+ currents (ICa) in nerve growth factor differientiated pheochromocytoma (PC12) cells using whole cell patch clamp techniques. PERC (100-1000 uM) inhibited ICa rapidly in a concentration-dependent and reversible manner; 1000 uM PERC completely suppressed ICa. When ICa was elicited by a step potential from -70 to +10 mV, 500 uM PERC inhibited peak ICa by 56 ? 3% and end ICa by 39 ? 6% (n=7), suggesting that end current is more sensitive to PERC effects than is peak current. PERC (500 uM) also shifted the voltage of half-maximal activation (V1/2) of ICa from -1.6 mV to -15.8 mV (n=5). As such, the current-voltage (I/V) relationship in the presence of PERC demonstrated increased ICa amplitude at hyperpolarized test potentials (-20 and -10 mV), but decreased ICa amplitude at test potentials greater than 0 mV (n=5). In addition, peak of the I/V relationship was shifted by approximately 10 mV to more hyperpolarized potentials. These results demonstrate that PERC blocks ICa at low micromolar concentrations, and suggest that effects on VGCC could contribute to the neurotoxicity of this solvent. (This abstract does not reflect EPA policy)