Post-junctional interactions between neuromuscular blocking agents and ethanol at the mouse neuromuscular junction
Article first published online: 2 JUN 2010
© 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society
British Journal of Pharmacology
Volume 161, Issue 3, pages 659–667, October 2010
How to Cite
Searl, T. and Silinsky, E. (2010), Post-junctional interactions between neuromuscular blocking agents and ethanol at the mouse neuromuscular junction. British Journal of Pharmacology, 161: 659–667. doi: 10.1111/j.1476-5381.2010.00904.x
- Issue published online: 3 SEP 2010
- Article first published online: 2 JUN 2010
- Received26 February 2010Revised21 April 2010Accepted27 April 2010
- non-depolarizing blockers
BACKGROUND AND PURPOSE Ethanol is known to have both pre-synaptic and post-synaptic effects at a range of loci in the mammalian nervous system, including the neuromuscular junction. However, the effects of ethanol on evoked synaptic transmission have not been previously studied at the mouse neuromuscular junction. Here, we report on the effects of ethanol on evoked neuromuscular transmission and the interaction of ethanol with non-depolarizing blocking drugs.
EXPERIMENTAL APPROACH Electrophysiological techniques to measure synaptic potentials and synaptic currents were employed in this study.
KEY RESULTS Ethanol (≥100 mM) produced increases in the amplitudes of both spontaneous and evoked synaptic events. Under conditions in which neuromuscular transmission was blocked by (+)-tubocurarine, ethanol (12–100 mM) produced greater increases in evoked response amplitude than in spontaneous response amplitude recorded in the absence of (+)-tubocurarine. Ethanol (100 mM) did not affect evoked neurotransmitter release in low-calcium/high-magnesium solutions. With respect to the clinically used neuromuscular blocking drugs, ethanol (100 mM) interfered with the blocking action of vecuronium, but not cisatracurium.
CONCLUSIONS AND IMPLICATIONS Under these conditions, the stimulant effect of ethanol on neuromuscular transmission is exclusively on the post-junctional elements, both to enhance transmission through nicotinic receptors and also via interactions with neuromuscular blocking agents. These actions of ethanol on neuromuscular transmission may affect the dosage of neuromuscular blockers required in patients who have imbibed significant amounts of alcohol.