Electrical and Mechanical Responses to Diltiazem in Potassium Depolarized Myocardium of the Guinea Pig

Effects of diltiazem on the electrical and mechanical activities of guinea pig papillary muscle were investigated in K-rich Tyrode's solution (Kc1 12.7 mM). The electrical properties of cell membrane in K-rich solution were also examined in the ventricular muscle fibers. It was found that the overshoot as well as the maximum rate of rise (Vmax) of the action potential were highly sensitive to the extracellular concentration of CaC12 in K-rich solution. Vmax was also affected by NaC1. Diltiazem at a lower concentration (1.1 X 10(-7) M) caused a reduction in the contractile force of K-depolarized papillary muscle without producing significant changes in the resting and action potentials. In the presence of a higher concentration of diltiazem (1.1 X 10(-5) M), the contractile force decreased concurrently with the change in the action potential. Addition of CaC12 restored the original strength of contraction in parallel to the recovery of the action potential, especially in its overshoot and Vmax. From these results, it is inferred that diltiazem may decrease the contractile force of guinea pig papillary muscle either by interfering with the intrasmembrane calcium influx or by intracellularly reducing the free calcium ion concentration in the myoplasm.