The mechanism for prejunctional enhancement of neuromuscular transmission by ethanol in the mouse.
Ethanol has been shown to have both presynaptic and postsynaptic effects on synaptic transmission. However, the mechanisms by which ethanol affects evoked neurotransmitter release have not been studied at the mouse neuromuscular junction, a synapse at which binomial analysis of neurotransmitter release and measurements of prejunctional ionic currents can be made. Ethanol (400 mM) increased neurotransmitter release independently of both the cAMP and phorbol ester/Munc13 signaling pathways. Binomial analysis of neurotransmitter release revealed that ethanol increases the average probability of secretion without an effect on the immediately available store of the neurotransmitter. Application of ethanol also resulted in an inhibition of potassium currents in the motor nerve endings. These results suggest that the potentiating effects of ethanol on neurotransmitter release at the skeletal neuromuscular junction are mediated by an inhibition of the delayed rectifier potassium current, thus increasing both calcium entry into the nerve ending and the probability of neurotransmitter release. Identifying the mechanism through which ethanol enhances neurotransmitter release at the neuromuscular junction may be useful in determining the processes underlying the enhancement of neurotransmitter release at other synapses.
Searl
T J
TJ
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA. tjs026@northwestern.edu
Silinsky
E M
EM
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D015233:Models, Statistical; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010703:Phorbol Esters / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D055366:Synaptic Potentials / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D015220:Calcium Channels; D010703:Phorbol Esters; D024642:Potassium Channels, Voltage-Gated; D000431:Ethanol; D011189:Potassium Chloride; D000242:Cyclic AMP; D002122:Calcium Chloride; D000109:Acetylcholine