Ethanol suppresses neuronal Ca2+ currents by effects on intracellular signal transduction.
The mechanism of action of ethanol on voltage-activated Ca2+ currents in neurons of the mollusk, Helix pomatia, was studied focusing on intracellular signaling. Ethanol suppressed inward Ca2+ currents in a time- and voltage-dependent manner. Buffering of intracellular Ca2+ with bis(o-aminophenoxy)ethane-N,N,N',N-tetraacetic acid (BAPTA) abolished the ethanol effects on Ca2+ currents. Intracellular GTP-gamma-S injection decreased Ca2+ currents whereas GDP-beta-S injection was ineffective. Ethanol had no further blocking effect on Ca2+ currents in GTP-gamma-S injected cells. In the presence of dopamine, which is known to suppress Ca2+ currents by G0-protein activation, ethanol application was ineffective. The protein kinase C (PKC) blockers, staurosporine and chelerythrine, prevented the ethanol effects on Ca2+ currents. The PKC activators, 1,2-oleoylacetylglycerol (OAG) and beta-phorbol-12,13-dibutyrate (PdBu), both, after maximum stimulation, also occluded the effect of ethanol on Ca2+ currents, whereas in the presence of 4-alpha-phorbol-12,13-didecanoate (4-alpha-PDD), an ineffective phorbol ester, ethanol suppressed Ca2+ currents. Ethanol increased the threshold of Ca2+-dependent action potentials and decreased their duration. Our results indicate that the suppression of voltage-activated Ca2+ currents by ethanol and its effects on action potentials involve activation of a G-protein/protein kinase transduction pathway.
Kerschbaum
H H
HH
Department of Physiology, Institute of Zoology, University of Salzburg, Austria.
Hermann
A
A
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002021:Buffers; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004594:Electrophysiology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000187:drug effects; D006372:Helix, Snails / Q000502:physiology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D002021:Buffers; D015220:Calcium Channels; D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D000431:Ethanol; D011494:Protein Kinases; D019204:GTP-Binding Proteins