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Title: Pathways mediating Ca2+ entry in rat cerebellar granule cells following in vitro exposure to methyl mercury.

Authors: Marty, M S; Atchison, W D

Published In Toxicol Appl Pharmacol, (1997 Dec)

Abstract: Cell imaging and the Ca(2+)-sensitive fluorophore fura-2 were used to examine methyl mercury's effect on Ca2+ homeostasis in rat cerebellar granule cells, a cell type preferentially targeted by methyl mercury. In vitro methyl mercury exposure (0.2-5.0 microM) induced a biphasic rise in fura-2 fluorescence ratio, consisting of a small first phase due to Ca2+ release from intracellular store(s) and a much larger second phase which required Ca2+ influx. The time-to-onset of these fura-2 fluorescence changes was inversely correlated with methyl mercury concentration. When examining various Ca2+ entry pathways as possible targets contributing to Ca2+ influx, we found that excitatory amino acid pathways were not directly involved. In contrast, the voltage-dependent Ca2+ channel blockers nifedipine and omega-conotoxin-MVIIC significantly delayed the time-to-onset of both phases, a response inconsistent with mere inhibition of Ca2+ entry. The nonselective voltage-dependent Ca2+ channel blocker Ni2+ had no effect on the methyl mercury response. Because methyl mercury alters cell membrane potentials, we hypothesized that voltage-dependent Na+ channels were activated initially; however, tetrodotoxin did not alter the methyl mercury-induced increases in fura-2 fluorescence ratio. Thus, methyl mercury alters Ca2+ homeostasis in cerebellar granule cells through nifedipine- and omega-conotoxin-MVIIC-sensitive pathways, suggesting that L-, N-, and/or Q-type Ca2+ channels may play a role in methyl mercury's mode of action or entry.

PubMed ID: 9439727 Exiting the NIEHS site

MeSH Terms: Animals; Calcium Channel Blockers/pharmacology; Calcium/metabolism*; Cell Membrane/metabolism; Cells, Cultured; Cerebellum/drug effects*; Cerebellum/metabolism*; Comparative Study; Excitatory Amino Acid Antagonists/pharmacology; Methylmercury Compounds/pharmacology*; Rats; Rats, Sprague-Dawley; Research Support, U.S. Gov't, P.H.S.; Tetrodotoxin/pharmacology

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