Effects of 4-aminopyridine on the excitation-contraction coupling in frog and rat skeletal muscle.

The effects of 4-aminopyridine (4-AP) were studied on isolated single muscle fibres of the frog and toe muscles of the rat. In both muscle preparations, 4-AP potentiated the twitch amplitude without significantly affecting the tetanus response. There was an increase of the time to peak tension and, in frog muscle, an increased time to half relaxation. 4-AP produced no change of the resting membrane potential. The rate of decay and, hence, the total duration of the action potential were markedly prolonged. 4-AP did not induce contractures by itself nor did it affect the contracture induced by caffeine. The mechanical threshold was determined by measuring the contracture response to various degrees of depolarization by potassium. This threshold was not affected by 4-AP. Twitch potentiation by 4-AP was independent of the extracellular calcium concentration. It is concluded that 4-AP potentiates the twitch response by increasing the release of activator calcium into the myofibrillar space by prolongation of the action potential. In addition, there may be a more direct inhibitory action of 4-AP on the calcium re-uptake by the sarcoplasmic reticulum in frog muscle.