SOME FEATURES OF THE EARLY STAGES OF NEUROMUSCULAR TRANSMISSION

Abstract

The responses of striated muscles to stimulation of their motor nerves were studied in cats. With a high frequency of stimulation the tension undergoes the following typical sequence of ups and downs. The initial rise (stage 1) is promptly followed by a fall (stage 2); a further rise (3a) is again followed by another fall (3b); a new rise (8c) marks the end of the "early" stages; these are followed by the "late" stages, fatigue (4) and a delayed rise (5). When tests are made with increasing frequency of stimulation stage 3b occurs with a lower rate than is necessary for the appearance of stage 2. Repetition of a high frequency results in the earlier development of the stages of depression 2 and 3b. The depressions are not due to corresponding decreases in the nerve impulses delivered to the muscles. The changes in tension are due to variations of contraction, not of contracture. After prostigmin the early stages may occur with quite slow frequencies. A brief period of stimulation at a rapid rate is usually followed by a delayed contraction. Acetylcholine and K have only a slight effect on stage 2. They accentuate the depression during stage 3b. Tetanic stimulation augments the muscular responses to acetylcholine and potassium. The changes of tension are due to presence or absence of transmission at some of the neuromuscular junctions[long dash]i.e., the stages denote changes of transmission. No explanation is available for stage 2. Stage 3b can be explained by the assumption of a paralytic effect of an excessive cone, of acetylcholine. The increased responsivity of muscle to nerve impulses, to acetylcholine, and to K after a period of tetanization may be due to a mobilization of K during the tetanus, but direct evidence is lacking of such mobilization and its mechanism.