The potentiating action of acetylcholine on the chemosensitivity of denervated skeletal muscle.

The acetylcholine sensitivity of soleus and extensor digitorum longus muscles of young rats was studied in vitro by measuring the isometric tension and membrane depolarisation developed in response to bath application of acetylcholine. Contractures of denervated muscles to acetylcholine gradually increased when the same concentration of acetylcholine was applied at 10 min intervals up to 60 min incubation whilst contractures evoked by potassium sulphate did not change significantly. The twitch tension of the muscles elicited in response to direct electrical stimulation did not increase and direct electrical stimulation failed to increase the acetylcholine sensitivity. Increased responses in vitro to acetylcholine were observed only in muscles denervated between 2 and 10 days previously with an optimum increase in sensitivity at 4-6 days. The increases in sensitivity were due to an action of acetylcholine since muscles left untreated exhibited no increases. Responses to carbamylcholine chloride, which is not hydrolysed by acetylcholinesterase, also increased. Membrane depolarisations in response to acetylcholine increased in a similar manner to the contracture responses in both soleus and extensor digitorum longus muscles, whilst the resting membrane potentials did not change. Denervated muscles which had been treated with acetylcholine bound more 125I-labelled alpha-bungarotoxin than muscles which had not been treated with acetylcholine. Denervated soleus muscles which had been previously blocked with unlabelled alpha-bungarotoxin responded to applications of acetylcholine with a gradually increasing depolarisation response and subsequently bound more [125I]alpha-bungarotoxin than muscles left without acetylcholine treatment. The possibility is discussed that acetylcholine acts upon the surface membranes of denervated muscles to increase the number of active acetylcholine receptors.