Effect of Diltiazem on Electrical and Mechanical Activity of Isolated Cardiac Ventricular Muscle of Guinea Pig

Diltiazem, a new 1,5-benzothiazepine derivative, antagonized calcium ion and thus caused a reduction in the contractile force of isolated papillary muscle. The antagonistic ratio of diltiazem to calcium ion was estimated to be approx. 1: 100. A lower concentration of diltiazem (2.2 x 10(-6) M) decreased the contractile force without affecting significantly the intracellularly recorded resting and action potentials. When the concentration of the compound was increased to 2.2 x 10(-5) M, only the maximum rate of rise of the action potential was reduced, while the other parameters of the action potential were also affected at 1.1 x 10(-4) M diltiazem. There was no significant change in the resting potential. Under conditions where the contractile force almost disappeared (1.1 x 10(-4) M), the membrane excitability was retained. It is concluded that diltiazem is an excitation-contraction uncoupler in the cardiac muscle cell and that the compound may exhibit its negative inotropic action by reducing in some way the intracellular concentration of free calcium ion available for the contractile mechanism.