Diazepam, a highly effective twitch potentiator in isolated muscle fibres of the frog

Abstract

The contractile effects of diazepam (10-200 microM) were studied on twitch and tetanus responses of isolated fibres of the semitendinosus muscle of Rana temporaria (3.5-5.0 degrees C). Diazepam (100-200 microM) enhanced the twitch amplitude to 95-100% of maximum tetanic force and increased the rate of rise of force, the time to peak twitch force and the total duration of the relaxation phase. The maximum tetanic output was unaffected by diazepam but the drug increased the rate of rise of the tetanic force and delayed the onset of force decay after the last stimulus. However, the kinetics of relaxation was unaffected by the drug. Diazepam had no effect on either threshold, submaximum or maximum contracture responses to caffeine and to increased potassium concentration. Diazepam in concentrations producing full twitch potentiation caused only a moderate (ca 30%) increase in action potential duration. The results are in line with the idea that 1: diazepam enhances the twitch response by increasing the rate of release of activator calcium without affecting the rate of calcium resequestration and 2: diazepam acts by modulating a mechanism in the excitation-contraction coupling that responds specifically to membrane excitation.