Twitch responses with acetylcholine in the isolated innervated and chronically denervated rat diaphragms and their modification by neuromuscular blocking agents

Abstract

Abstract The increased sensitivity to acetylcholine after chronic denervation was investigated by retrograde injection of the acetylcholine into the venous drainage of the isolated diaphragm of the rat set up in Krebs solution at 38°. Supersensitivity of the twitch response was observed 3 days after nerve section and developed further to reach a peak at the eighth to tenth day after denervation and then slowly declined with atrophy of the muscle. At the time of the onset of supersensitivity the degenerating peripheral nerve stump failed to respond to electrical stimulation and fibrillation of the muscle was observed. The muscle also responded to acetylcholine and other depolarising drugs by giving a contracture. After denervation, the response to injected acetylcholine was more sensitive to block by depolarising neuromuscular blocking agents but not to block by competitive blocking drugs. Tubocurarine did not cause a stimulation on injection into denervated muscle, while decamethonium gave an acetylcholine-like response. The significance of the observations is discussed.