Feedback of isotonic muscle contraction on neuromuscular impulse transmission in the frog.

The effect of isotonic contraction on neuromuscular impulse transmission was studied in the in vivo M. gastrocnemius preparation of the frog. The N. ischiadicus was stimulated regularly with single pulses at different frequencies in the range of 1/8 to 8 Hz. When steady state conditions were reached, each half-minute a second stimulus was added to one of these pulses. The interval between the pulses of the pair was varied within the contraction cycle of the first stimulus. Compound extracellular or single intracellular action potentials were recorded from the muscle. At frequencies of 1/2-2 Hz a depression of the amplitude of the second compound muscle action potential of up to 50% of the first response was found when the muscle contracted isotonically. However, the second response was facilitated during an isometric contraction. The time course of the depression was equal to that of muscle shortening during the twitch, while the time course of facilitation corresponded roughly to that of facilitation of transmitter release. At lower frequencies the "isotonic depression" or "isometric facilitation" was not or only slightly present. However, at 1/8 Hz the depression could be evoked or increased by curarization. At frequencies higher than 2 Hz facilitation dominated over depression under isotonic conditions. With flexible intracellular micro-electrodes it was shown that the depression of the amplitude of the compound muscle action potential observed during the isotonic twitch was due to a reduction in neuromuscular impulse transmission. It is concluded that the isotonic depression is a negative feedback effect of the change of length of the contracting muscle on synaptic impulse transmission, probably due to an effect of length on transmitter release.