Pathways Mediating Ca 2+ Entry in Rat Cerebellar Granule Cells Following in Vitro Exposure to Methyl Mercury

Pathways Mediating Ca 2+ Entry in Rat Cerebellar Granule Cells Following in Vitro Exposure to... Cell imaging and the Ca 2+ -sensitive fluorophore fura-2 were used to examine methyl mercury's effect on Ca 2+ homeostasis in rat cerebellar granule cells, a cell type preferentially targeted by methyl mercury. In vitro methyl mercury exposure (0.2–5.0 μ m ) induced a biphasic rise in fura-2 fluorescence ratio, consisting of a small first phase due to Ca 2+ release from intracellular store(s) and a much larger second phase which required Ca 2+ influx. The time-to-onset of these fura-2 fluorescence changes was inversely correlated with methyl mercury concentration. When examining various Ca 2+ entry pathways as possible targets contributing to Ca 2+ influx, we found that excitatory amino acid pathways were not directly involved. In contrast, the voltage-dependent Ca 2+ channel blockers nifedipine and ω-conotoxin-MVIIC significantly delayed the time-to-onset of both phases, a response inconsistent with mere inhibition of Ca 2+ entry. The nonselective voltage-dependent Ca 2+ channel blocker Ni 2+ 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 Ca 2+ homeostasis in cerebellar granule cells through nifedipine- and ω-conotoxin-MVIIC-sensitive pathways, suggesting that L-, N-, and/or Q-type Ca 2+ channels may play a role in methyl mercury's mode of action or entry. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Toxicology and Applied Pharmacology Elsevier

Pathways Mediating Ca 2+ Entry in Rat Cerebellar Granule Cells Following in Vitro Exposure to Methyl Mercury

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Publisher
Elsevier
Copyright
Copyright © 1997 Academic Press
ISSN
0041-008x
D.O.I.
10.1006/taap.1997.8262
Publisher site
See Article on Publisher Site

Abstract

Cell imaging and the Ca 2+ -sensitive fluorophore fura-2 were used to examine methyl mercury's effect on Ca 2+ homeostasis in rat cerebellar granule cells, a cell type preferentially targeted by methyl mercury. In vitro methyl mercury exposure (0.2–5.0 μ m ) induced a biphasic rise in fura-2 fluorescence ratio, consisting of a small first phase due to Ca 2+ release from intracellular store(s) and a much larger second phase which required Ca 2+ influx. The time-to-onset of these fura-2 fluorescence changes was inversely correlated with methyl mercury concentration. When examining various Ca 2+ entry pathways as possible targets contributing to Ca 2+ influx, we found that excitatory amino acid pathways were not directly involved. In contrast, the voltage-dependent Ca 2+ channel blockers nifedipine and ω-conotoxin-MVIIC significantly delayed the time-to-onset of both phases, a response inconsistent with mere inhibition of Ca 2+ entry. The nonselective voltage-dependent Ca 2+ channel blocker Ni 2+ 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 Ca 2+ homeostasis in cerebellar granule cells through nifedipine- and ω-conotoxin-MVIIC-sensitive pathways, suggesting that L-, N-, and/or Q-type Ca 2+ channels may play a role in methyl mercury's mode of action or entry.

Journal

Toxicology and Applied PharmacologyElsevier

Published: Dec 1, 1997

References

  • The novel anticonvulsant MK-801 binds to the activated state of the N d
    Foster, A.C.; Wong, E.H.
  • Kinetic and pharmacological properties distinguish three types of calcium current in chick sensory neurones
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    Hare, M.F.; Atchison, W.D.
  • Bradykinin-activated calcium influx pathway in bovine aortic endothelial cells
    Mendelowitz, D.; Bacal, K.; Kunze, D.L.
  • Basis of tetrodotoxin's selectivity in blockage of squid axons
    Moore, J.W.; Blaustein, M.P.; Anderson, N.C.; Narahashi, T.
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    Redman, R.S.; Silinsky, E.M.
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    Winegar, B.D.; Kelly, R.; Lansman, J.B.

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