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Ethanol Alters Opioid Regulation of Ca2+ Influx Through L-Type Ca2+ Channels in PC12 Cells

Authors

  • Donna L. Gruol,

    1. From the Molecular and Integrative Neurosciences Department (DLG, TEN, CH, SM), The Scripps Research Institute, La Jolla, California; and Department of Clinical Neuroscience (VV, YM, LT), Karolinska Institute, Stockholm, Sweden.
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  • Thomas E. Nelson,

    1. From the Molecular and Integrative Neurosciences Department (DLG, TEN, CH, SM), The Scripps Research Institute, La Jolla, California; and Department of Clinical Neuroscience (VV, YM, LT), Karolinska Institute, Stockholm, Sweden.
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  • Christine Hao,

    1. From the Molecular and Integrative Neurosciences Department (DLG, TEN, CH, SM), The Scripps Research Institute, La Jolla, California; and Department of Clinical Neuroscience (VV, YM, LT), Karolinska Institute, Stockholm, Sweden.
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  • Sarah Michael,

    1. From the Molecular and Integrative Neurosciences Department (DLG, TEN, CH, SM), The Scripps Research Institute, La Jolla, California; and Department of Clinical Neuroscience (VV, YM, LT), Karolinska Institute, Stockholm, Sweden.
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  • Vladana Vukojevic,

    1. From the Molecular and Integrative Neurosciences Department (DLG, TEN, CH, SM), The Scripps Research Institute, La Jolla, California; and Department of Clinical Neuroscience (VV, YM, LT), Karolinska Institute, Stockholm, Sweden.
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  • Yu Ming,

    1. From the Molecular and Integrative Neurosciences Department (DLG, TEN, CH, SM), The Scripps Research Institute, La Jolla, California; and Department of Clinical Neuroscience (VV, YM, LT), Karolinska Institute, Stockholm, Sweden.
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  • Lars Terenius

    1. From the Molecular and Integrative Neurosciences Department (DLG, TEN, CH, SM), The Scripps Research Institute, La Jolla, California; and Department of Clinical Neuroscience (VV, YM, LT), Karolinska Institute, Stockholm, Sweden.
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Reprint requests: Donna L. Gruol, PhD, Molecular and Integrative Neurosciences Department, SP30-1522, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; Tel.: 858-784-7060; Fax: 858-784-7393; E-mail: gruol@scripps.edu

Abstract

Background:  Studies at the behavioral and synaptic level show that effects of ethanol on the central nervous system can involve the opioid signaling system. These interactions may alter the function of a common downstream target. In this study, we examined Ca2+ channel function as a potential downstream target of interactions between ethanol and μ or κ opioid receptor signaling.

Methods:  The studies were carried out in a model system, undifferentiated PC12 cells transfected with μ or κ opioid receptors. The PC12 cells express L-type Ca2+ channels, which were activated by K+ depolarization. Ca2+ imaging was used to measure relative Ca2+ flux during K+ depolarization and the modulation of Ca2+ flux by opioids and ethanol.

Results:  Ethanol, μ receptor activation, and κ receptor activation all reduced the amplitude of the Ca2+ signal produced by K+ depolarization. Pretreatment with ethanol or combined treatment with ethanol and μ or κ receptor agonists caused a reduction in the amplitude of the Ca2+ signal that was comparable to or smaller than that observed for the individual drugs alone, indicating an interaction by the drugs at a downstream target (or targets) that limited the modulation of Ca2+ flux through L-type Ca2+ channels.

Conclusions:  These studies provide evidence for a cellular mechanism that could play an important role in ethanol regulation of synaptic transmission and behavior through interactions with the opioid signaling.

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