Effect of bepridil on intracellular calcium concentration and contraction in cultured rat ventricular myocytes.

We studied the effects of a new antiarrhythmic and antianginal agent, bepridil, on the intracellular calcium transient and contraction of cultured neonatal rat ventricular cells. and compared the effects with those caused by an authentic Ca 2+ -entry blocker, D600 (methoxyverapamil). The Ca 2+ transient was measured by using dual-wavelength microfluorometry of fura-2. The contraction was measured as a shortening of cell aggregates with the use of a video image-analyzing system. Both bepridil (1-30 μM) and D600 (1-30 μM) decreased the peak systolic amplitude of the Ca 2+ transient in a concentration- and frequency-dependent manner. Bepridil, but not D600, significantly shortened the half-decay time of the Ca 2+ transient and prolonged the time course of the contraction. D600 decreased the contraction in parallel with the decrease in the peak Ca 2+ transient, whereas bepridil exerted no significant effect on the contraction. Bepridil (10 μM) induced a leftward shift (to lower amplitude of peak systolic Ca 2+ transient) of the relation between the magnitude of contraction and the peak systolic Ca 2+ transient, which was obtained by changing external Ca 2+ concentration. In contrast. D600 (10 μM) did not affect the relation. The results suggest that the negative inotropic effect of bepridil (caused by its Ca 2+ channel-blocking effect) is offset by its simultaneous increase in the sensitivity of contractile protein(s) to intracellular Ca 2+ , which may be a unique characteristic of this antiarrhythmic agent in a clinical setting.