Blocking action of succinylcholine with beta-eudesmol on acetylcholine-activated channel activity at endplates of single muscle cells of adult mice.
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.
Nojima
H
H
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Kimura
I
I
Kimura
M
M
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D051379:Mice; D009045:Motor Endplate / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism*; D045787:Sesquiterpenes, Eudesmane; D013390:Succinylcholine / Q000494:pharmacology*; D013569:Synapses / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*
D045787:Sesquiterpenes, Eudesmane; D013729:Terpenes; C051082:beta-eudesmol; D013390:Succinylcholine; D000109:Acetylcholine