SUBACUTE DENERVATION: A MEANS OF DISCLOSING MAMMALIAN MOTOR NERVE TERMINALS AS CRITICAL SITES OF ACETYLCHOLINE AND FACILITATORY DRUG ACTIONS

¹ Department of Pharmacology, Cornell University Medical College, New York, New York

In the cat 48 hr after motor nerve section (subacute denervation), the contractile response to i.a. injected acetyicholine (ACh) is greatly diminished. Nevertheless, the denervated muscle always exhibits some response to single supramaximal nerve stimulation. Often this response is at or near normal. Despite this, the twitch potentiation ordinarily produced by physostigmine-like drugs is poor or absent. Accordingly, it was found that the 48-hr denervated terminals generate little or no repetition after exposure to these drugs. Also physostigmine causes little fasciculation 48 hr after nerve section. Not least is the finding that ACh action is not augmented by physostigmine pretreatment in subacute denervation. From the foregoing data, it is concluded that the functional integrity of the unmyelinated terminals is essential for the action of physostigmine-like drugs and ACh. The results support the conclusion that these drugs act directly on the terminal membrane. The technique of subacute denervation provides a relatively simple means of testing motor nerve terminal participation in drug action at the neuromuscular junction.

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