Ethanol alters opioid regulation of Ca(2+) influx through L-type Ca(2+) channels in PC12 cells
Donna L Gruol1, Thomas E Nelson, Christine Hao
1Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037, USA.
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 micro or κ opioid receptor signaling.
Methods:
The studies were carried out in a model system, undifferentiated PC12 cells transfected with micro 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, micro 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 micro 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.
Insights
Ethanol and opioid receptor signaling interact at a common downstream target, affecting calcium (Ca2+) channel function. This interaction influences synaptic transmission and behavior.
Area of Science:
- Neuroscience
- Cellular Biology
- Pharmacology
Background:
- Ethanol's central nervous system effects involve opioid signaling.
- Interactions between ethanol and opioid receptors may affect common downstream targets.
- Calcium (Ca2+) channel function is investigated as a potential shared target.
Purpose of the Study:
- To examine Ca2+ channel function as a downstream target of ethanol and opioid receptor interactions.
- To understand the cellular mechanisms underlying ethanol-opioid signaling interplay.
Main Methods:
- Experiments utilized undifferentiated PC12 cells expressing micro or kappa opioid receptors.
- L-type Ca2+ channels in PC12 cells were activated by K+ depolarization.
- Ca2+ imaging measured Ca2+ flux modulation by ethanol and opioid receptor activation.
Main Results:
- Ethanol, micro-receptor activation, and kappa-receptor activation independently reduced Ca2+ signal amplitude.
- Combined ethanol and opioid treatment resulted in Ca2+ signal reduction comparable to or less than individual treatments.
- Evidence suggests interaction at downstream targets limiting Ca2+ flux modulation via L-type Ca2+ channels.
Conclusions:
- Provides evidence for a cellular mechanism in ethanol's regulation of synaptic transmission.
- Highlights the role of opioid signaling interactions in ethanol's behavioral effects.
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