MECHANISM OF THE BLOCKING ACTION OF BETA-EUDESMOL ON THE NICOTINIC ACETYLCHOLINE-RECEPTOR CHANNEL IN MOUSE SKELETAL-MUSCLES

Beta-Eudesmol, an uncharged alcohol contained in Atractylodes lancea, blocks the neuromuscular junction. Atractylodes lancea is prescribed in a traditional Chinese medicine and plays a main role for "alleviation of pain in skeletal muscle". By using the cell-attached patch-clamp or conventional intracellular technique, the site of action of beta-eudesmol on the nicotinic acetylcholine (ACh) receptor (nAChR) channel in skeletal muscle of the adult mouse, was investigated and compared with that of different types of blockers of the nicotinic ACh receptor channel (bupivacaine, chlorpromazine and phencyclidine). Beta-Eudesmol (200-mu-M) depressed completely the nerve-evoked twitch tension and reduced the amplitude and quantal size of endplate potentials but did not alter either the quantal content, resting membrane potential or action potential. Beta-Eudesmol (100-200-mu-M) decreased the amplitude of ACh potentials and accelerated the slow decay of depolarization, induced by the continuous application of ACh. Beta-Eudesmol (40-mu-M) and phencyclidine (10-mu-M) decreased both the open time and opening frequency, without affecting the single channel conductance. Bupivacaine (10-mu-M) decreased only the open time. Chlorpromazine (10-mu-M) decreased only the opening frequency. These results indicate that the blocking effect of beta-eudesmol on nerve-evoked contraction, was due to blockade of nicotinic ACh receptor channels at the neuromuscular junction. Like phencyclidine, beta-eudesmol blocked the nicotinic ACh receptor channel in both the open and closed conformations, and accelerated the desensitization of the nicotinic ACh receptor.