M. Jonsson, M. Dabrowski, D. Gurley
Apr 1, 2006
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Journal
Anesthesiology
Abstract
Background: Succinylcholine is one of the most widely used muscle relaxants in clinical anesthesia and emergency medicine. Although the clinical advantages and cardiovascular side effects are well known, its mechanism of action within the human nicotinic cholinergic receptor system remains to be understood. The aim of this study was to investigate the effect of succinylcholine on human muscle and neuronal nicotinic acetylcholine receptor (nAChR) subtypes. Methods: Xenopus laevis oocytes were injected with human messenger RNA for muscle and neuronal nAChR subunits. Receptor activation, desensitization, and inhibition induced by the natural ligand acetylcholine or by succinylcholine was studied using a multichannel two-electrode voltage clamp setup. Responses were measured as peak current and net charge. Results: Succinylcholine concentration-dependently activated the muscle-type nAChR with an EC50 value of 10.8 &mgr;m (95% confidence interval, 9.8–11.9 &mgr;m), and after the initial activation, succinylcholine desensitized the muscle-type nAChR. Succinylcholine did not activate the neuronal nAChR subtypes α3β2, α3β4, α4β2, or α7 at concentrations up to 1 mm and was a poor inhibitor at these receptor subtypes, with IC50 values above 100 &mgr;m. Conclusion: Succinylcholine activates the muscle-type nAChR followed by desensitization. The observation that succinylcholine does not inhibit the presynaptic α3β2 autoreceptor at clinically relevant concentrations provides a possible mechanistic explanation for the typical lack of tetanic fade in succinylcholine-induced neuromuscular blockade. Finally, cardiovascular side effects (e.g., tachyarrhythmias) of succinylcholine are not mediated via direct activation of the autonomic ganglionic α3β4 subtype because succinylcholine does not activate the neuronal nAChRs.