Ethanol alters opioid regulation of Ca(2+) influx through L-type Ca(2+) channels in PC12 cells

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.