Studies on the mechanism of the excitation-contraction coupling in cardiac muscle, with special reference to the caffeine-contracture.

Abstract

In order to clarify the mechanism of the excitation-contraction coupling of the cardiac muscle, the effect of caffeine on the cardiac ventricular strip of the frog was studied under various conditions and following results were obtained.1. In normal Ringer solution, caffeine (5-50mM) did not cause the contracture of the strip.Under the same condition, however, caffeine affected the automaticity and the contractility of the strip; a contractility increased at the low concentration (about 5-10mM of caffeine) and decreased at the high concentration (about 20-50mM), and the alternations of automaticity occurred arhythmia and arrest of pulsation. Even in the case of the arrest of pulsation, the mechanical responses to the electrical stimuli were observed.2. The high concentration of caffeine (50mM) caused decrease of both resting potential and duration of plateau of the action potential, but these changes were recovered in the normal Ringer solution. This indicates that the effects of caffeine are perfectly reversible.3. By the prolonged immersion in the high concentration of caffeine, the contraction by electrical stimuli was limited to a localized area.4. One of the conditions for inducing caffeine-contracture is the deficiency of sodium in the bathing solution, that is, the contracture occurred in the Ringer solutions of which sodium was replaced by KCl, choline chloride or nonelectrolytes (sucrose, glucose and glycerine). The other condition indispensable for inducing the contracture was the existence of calcium which could be removed by the application of chelating agent. The treatment by Ca-free medium was not sufficient enough to remove the calcium from the cell.5. The grade of the contracture was dependent on the concentration of calcium and sodium contained in the Ringer solution; at the constant concentration of sodium, the grade was higher in the higher concentration of calcium; at the constant concentration of calcium, the grade was lower in the higher concen tration of sodium.From these results, the mechanism of the excitation-contraction coupling and the affected site by caffeine were discussed in comparison with the case of the skeletal muscle.