Effects of Chlorpromazine, Imipramine, and Quinidine on Action Potential and Tension Development in Single Skeletal Muscle Fibres of the Frog

Abstract

Abstract The effects of chlorpromazine, imipramine, and quinidine on resting membrane potential, action potential, twitch and tetanic tensions, and on the active state were investigated in single frog skeletal muscle fibres. Chlorpromazine in concentrations 10 ‐6 –10 ‐5 M, and imipramine and quinidine in concentrations 10 ‐5 –5 × 10 ‐5 M, did not affect the resting membrane potential but produced a dose‐dependent decrease in the rate of rise, rate of fall, and overshoot of the action potential. The duration, measured at –50 mV, was prolonged. The drugs potentiated the isometric twitch by increasing the duration of the active state. Tetanic tension was not affected. In high concentrations (chlorpromazine 3 × 10 ‐5 M, imipramine and quinidine > 5 × 10 ‐5 M) the drugs caused a successive widening and decrease of amplitude of the action potential and finally blocked the electrical activity. After a marked initial increase, the peak twitch tension was reduced in parallel with the changes of the action potential. The reduction in twitch amplitude was probably due to incomplete activation of the fibres. The mechanisms of the effects on the excitation‐contraction coupling induced by chlorpromazine, imipramine, and quinidine are discussed.