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Ethanol Alters Opioid Regulation of Ca 2+ Influx Through L‐Type Ca 2+ Channels in PC12 Cells
Author(s) -
Gruol Donna L.,
Nelson Thomas E.,
Hao Christine,
Michael Sarah,
Vukojevic Vladana,
Ming Yu,
Terenius Lars
Publication year - 2012
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2011.01631.x
Subject(s) - depolarization , chemistry , biophysics , opioid receptor , opioid , receptor , ethanol , neurotransmission , biochemistry , biology
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 Ca 2+ 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 Ca 2+ channels, which were activated by K + depolarization. Ca 2+ imaging was used to measure relative Ca 2+ flux during K + depolarization and the modulation of Ca 2+ flux by opioids and ethanol.Results: Ethanol, μ receptor activation, and κ receptor activation all reduced the amplitude of the Ca 2+ 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 Ca 2+ 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 Ca 2+ flux through L‐type Ca 2+ 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.