Protein kinase C ε mediates up-regulation of N-type calcium channels by ethanol

Thomas Mcmahon, Reid Andersen, Pamela Metten, John Jr Crabbe, Robert O. Messing

Research output: Contribution to journalArticle

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Abstract

Brief exposure to ethanol inhibits L-type and N-type voltage-gated calcium channels in neural cells. Although chronic ethanol exposure up- regulates the density and function of L-type channels via a protein kinase C (PKC) δ-dependent mechanism, the effect of prolonged ethanol exposure on N- type channels is not known. Using PC12 cells, we found that exposure to 25 to 150 mM ethanol for 0 to 8 days produced a time- and concentration-dependent increase in the density of binding sites for the N-type channel antagonist 125I-ω-conotoxin GVIA. This was associated with an increase in ω- conotoxin GVIA-sensitive, depolarization-evoked rises in [Ca2+](i). Increases in 125I-ω-conotoxin GVIA binding also were observed in the frontal cortex and the hippocampus, but not in the thalamus of mice exposed to ethanol vapor for 3 days. In PC12 cells, increases in 125I-ω-conotoxin GVIA binding were blocked by the PKC inhibitor bisindolylmaleimide I and by expression of a selective peptide inhibitor of PKCE. Expression of a selective inhibitor of PKCδ did not alter ethanol-induced increases in 125I-ω-conotoxin GVIA binding. These findings indicate that PKCε mediates upregulation of N-type channels by ethanol. Because N-type channels modulate calcium-dependent neurotransmitter release, these findings suggest a mechanism that may contribute to neuronal hyperexcitability observed during alcohol withdrawal.

Original languageEnglish (US)
Pages (from-to)53-58
Number of pages6
JournalMolecular Pharmacology
Volume57
Issue number1
StatePublished - 2000

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N-Type Calcium Channels
Conotoxins
Protein Kinase C
Ethanol
Up-Regulation
PC12 Cells
Protein C Inhibitor
Frontal Lobe
Calcium Channels
Protein Kinase Inhibitors
Thalamus
Neurotransmitter Agents
Hippocampus
Binding Sites
Alcohols
Peptides

ASJC Scopus subject areas

  • Pharmacology

Cite this

Mcmahon, T., Andersen, R., Metten, P., Crabbe, J. J., & Messing, R. O. (2000). Protein kinase C ε mediates up-regulation of N-type calcium channels by ethanol. Molecular Pharmacology, 57(1), 53-58.

Protein kinase C ε mediates up-regulation of N-type calcium channels by ethanol. / Mcmahon, Thomas; Andersen, Reid; Metten, Pamela; Crabbe, John Jr; Messing, Robert O.

In: Molecular Pharmacology, Vol. 57, No. 1, 2000, p. 53-58.

Research output: Contribution to journalArticle

Mcmahon, T, Andersen, R, Metten, P, Crabbe, JJ & Messing, RO 2000, 'Protein kinase C ε mediates up-regulation of N-type calcium channels by ethanol', Molecular Pharmacology, vol. 57, no. 1, pp. 53-58.
Mcmahon, Thomas ; Andersen, Reid ; Metten, Pamela ; Crabbe, John Jr ; Messing, Robert O. / Protein kinase C ε mediates up-regulation of N-type calcium channels by ethanol. In: Molecular Pharmacology. 2000 ; Vol. 57, No. 1. pp. 53-58.
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