Blocking action of succinylcholine with β-eudesmol on acetylcholine-activated channel activity at endplates of single muscle cells of adult mice

Abstract

The neuromuscular blockade produced by succinylcholine (SuCh) is potentiated by beta-eudesmol, a sesquiterpenoid alcohol isolated from Atractylodes lancea. beta-Eudesmol blocks the nicotinic acetylcholine receptor (nAChR) channel in both open and closed conformations. To clarify the mechanism of potentiation, we investigated the blocking effect of SuCh (0.1-10 microM) with beta-eudesmol on nAChR channel activity using the cell-attached patch clamp technique. Pretreatment with beta-eudesmol (20 microM) affected neither resting membrane potential nor ACh-activated channel activities. beta-Eudesmol produced the following changes in ACh-activated channel currents modulated by SuCh: reduction of SuCh (above 0.3 microM)-induced prolongation of channel open time and decrease in the frequency of channel opening in the presence of SuCh (above 3 microM). These results suggest that the potentiating effect of beta-eudesmol is postsynaptically due to accelerated desensitization of the nAChR, presumably resulting from preferential blocking action during the closed state of the receptor channel.