Methylmercury Affects Multiple Subtypes of Calcium Channels in Rat Cerebellar Granule Cells

doi:10.1006/taap.2000.8967

Toxicology and Applied Pharmacology

Volume 167, Issue 1, 15 August 2000, Pages 1-11

https://doi.org/10.1006/taap.2000.8967 Get rights and content

Abstract

We tested the ability of methylmercury (MeHg) to block calcium channel current in cultures of neonatal cerebellar granule cells using whole-cell patch clamp techniques and Ba²⁺ as charge carrier. Low micromolar concentrations of MeHg (0.25–1 μM) reduced the amplitude of whole cell Ba²⁺ current in a concentration- and time-dependent fashion; however, this effect was not voltage-dependent and the current–voltage relationship was not altered. Increasing the stimulation frequency hastened the onset and increased the magnitude of block at both 0.25 and 0.5 μM MeHg but not at 1 μM. In the absence of stimulation, all concentrations of MeHg were able to decrease current amplitude. The ability of several Ca²⁺ channel antagonists (ω-conotoxin GVIA, ω-conotoxin MVIIC, ω-agatoxin IVA, calcicludine, and nimodipine) to alter the MeHg-induced effect was tested in an effort to determine if MeHg targets a specific subtype of Ca²⁺ channel. Each of the antagonists tested was able to decrease a portion of whole cell Ba²⁺ current under control conditions. However, none were able to attenuate the MeHg-induced block of whole cell Ba²⁺ current, suggesting either that the mechanism of MeHg-induced block involves sites other than those influenced specifically by Ca²⁺ channel antagonists or that MeHg was able to “outcompete” these toxins for their binding sites. These results show that acute exposure to submicromolar concentrations of MeHg can block Ba²⁺ currents carried through multiple Ca²⁺ channel subtypes in primary cultures of cerebellar granule cells. However, it is unlikely that the presence of a specific Ca²⁺ channel subtype is able to render granule cells more susceptible to the neurotoxicologic actions of MeHg.

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^☆: Preliminary results of parts of this paper were presented in abstract form at the 35th Annual Meeting of the Society of Toxicology and were published in abstract form in The Toxicologist,30(26), 1996. This paper was submitted by J.E.S. in partial fulfillment of the requirements for the Ph.D. degree in Pharmacology and Toxicology and Environmental Toxicology at Michigan State University.

²: Present address: Department of Pharmacology, University of Virginia Health Sciences Center, Jordan Hall, HSC Box 448, Charlottesville, Virginia, 22908.

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Regular ArticleMethylmercury Affects Multiple Subtypes of Calcium Channels in Rat Cerebellar Granule Cells☆

Abstract

Toxicol. Lett.

Toxicol. Appl. Pharmacol.

Prog. Biophys. Mol. Biol.

Neuropharmacology

Toxicol. Appl. Pharmacol.

J. Biol. Chem.

J. Mol. Cell. Cardiol.

Toxicol. Appl. Pharmacol.

Neuron

J. Biol. Chem.

Chem.–Biol. Interact.

Toxicol. Appl. Pharmacol.

Toxicol. Appl. Pharmacol.

Toxicol. Appl. Pharmacol.

Neuron

J. Biol. Chem.

Neuropharmacology

Curr. Opin. Neurobiol.

Neuron

Toxicol. Lett.

J. Biol. Chem.

Toxicol. Appl. Pharmacol.

Trends Neurosci.

Neuropharmacology

The effects of activation of sodium and calcium entry on spontaneous release of acetylcholine induced by methylmercury

J. Pharmacol. Exp. Ther.

Methylmercury-induced depression of neuromuscular transmission in the rat

NeuroToxicology

Irreversible suppression of calcium entry into nerve terminals by methylmercury

J. Pharmacol. Exp. Ther.

Methylmercury poisoning in Iraq

Science.

Mercurial-induced alterations in neuronal divalent cation homeostasis

NeuroToxicology

Calcium-mediated inactivation of the calcium conductance in caesium-loaded giant neurones of Aplysia californica

J. Physiol. (Lond.)

Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones

J. Physiol.

Calcium channel

Annu. Rev. Neurosci.

Regular Article
Methylmercury Affects Multiple Subtypes of Calcium Channels in Rat Cerebellar Granule Cells☆