PHARMACOLOGIC EVIDENCE FOR THE EXISTENCE OF A PRESYNAPTIC EVENT IN NEUROMUSCULAR TRANSMISSION

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

Using an in situ nerve-muscle preparation of the cat, considerable evidence has been cumulated to confirm the fact that 3-hydroxy phenyl-triethyl ammonium ion (3-OH PTEA) exerts an action on the motor nerve terminal. This action is facilitatory in nature and consists in the appearance of repetitive activity in muscle and potentiation of twitch tension in response to a single maximal nerve volley. Repetitive activity usually also appears in the motor nerve; this is detected antidromically in ventral root fibers.

Following tine intraarterial administration of 3-OH PTEA in 37 experiments, repetitive activity appeared in the motor nerve in of the animals. In those cats thnat did not exhibit repetitive nerve activity after 3-OH PTEA, it was proved that neither inadequate dosage nor faulty preparation was responsible. Rather, the action of 3-OH PTEA on the motor nerve terminal is viewed tts initiating "forward" and "backward" responses. Tlne latter, reexcitation of the axon from the terminal, must therefore occur only under unusual conditions in comparison with transmission. In any case tine circumstances reveal the motor nerve terminal as functionally intermediate to the motor nerve axon and the end plate.

Separation of forward and backward responses to 3-OH PTEA, and thereby the distinction of the motor nerve termimnal, was also achieved pharmacologically. In those animals that manifested repetitive antidromic discharge in motor nerve after 3-OH PTEA, stabilization of the neuronal structure was easily accomplished with neurotropic depressant drugs. Accordingly, pentobarbital, cyclopropane and procaine suppressed backfiring in motor nerve. In these experimemnts the neural reflection of 3-OH PTEA was always more vulnerable than the forward effect; mnnumscle and twitch potentiation were considerably more resistant.

The physiologic relevamnce of these findings for neuromuscular transmission is discussed.