You are here:
SUB-ACUTE TREATMENT WITH METHYLMERCURY DURING DIFFERENTIATION OF PHEOCHROMOCYTOMA (PC12) CELLS DOES NOT ALTER BINDING OF ION CHANNEL LIGANDS OR CELL MORPHOLOGY.
Citation:
Shafer, T J., S Barone, AND C A. Meacham. SUB-ACUTE TREATMENT WITH METHYLMERCURY DURING DIFFERENTIATION OF PHEOCHROMOCYTOMA (PC12) CELLS DOES NOT ALTER BINDING OF ION CHANNEL LIGANDS OR CELL MORPHOLOGY. Presented at Society of Toxicology, San Francisco, CA, March 25-29, 2001.
Description:
We demonstrated recently that 6 days of exposure to nanomolar concentrations (3-10 nM) of methylmercury (MeHg) during nerve growth factor (NGF) induced PC12 cell differentiation reduced the amplitude and density of voltage-gated sodium and calcium currents. In the present study, the specific binding of 3[H]saxitoxin and -[125I]conotoxin GVIA were examined to test the hypothesis that the reductions in current were the result of decreased expression of voltage-gated sodium and N-type voltage-sensitive calcium channels, respectively. Following treatment with up to 10 nM MeHg in the presence of NGF for 6 days, there was no difference in the values for KD or Bmax for saxitoxin binding when control and MeHg-treated cells were compared. Similarly, there was no difference in the binding of -[125I]conotoxin GVIA between control and MeHg-treated cells. To test the hypothesis that alterations in ion channel function during differentiation may result in morphological alterations in PC12 cells, quantitative morphometrical analysis of cell body area, total neurite outgrowth, and number of neurite branches was carried out. PC12 cells were plated onto glass coverslips coated with polylysine and exposed to methylmercury (0-20 nM) for 6 days in the presence of NGF. There were no treatment-related changes in any of the morphological parameters examined. However, neurite outgrowth in control cells was 30-40% of neurite outgrowth of historical controls plated on plastic coated with collagen. These results suggest that decreases in voltage-gated sodium and N-type voltage-sensitive calcium currents are not the result of MeHg-induced decreases in the expression of voltage-gated ion channels, but rather may be the result of direct inhibition of ion channel function or decreased ion channel conductance. In addition, the present results suggest that decreases in voltage-gated currents occur in the absence of morphological alterations of PC12 cells. (This abstract does not necessarily reflect EPA policy).