Effects of a newly synthesized dihydropyridine, NZ-105, on intracellular Ca transients and tension in ferret ventricular muscles.

We investigated the effects of a newly synthesized dihydropyridine (DHP) derivative (NZ-105) on intracellular Ca transients and contraction in ferret ventricular muscles, using the aequorin method. Low concentrations of NZ-105 (10(-9)-10(-7) M) showed no significant effects on the light signal of aequorin and tension in twitch. High concentrations of NZ-105 (10(-6)-10(-5) M) inhibited the peaks of the light signal and tension without altering their time courses. The relation between the peaks of the light signal and tension in twitch, measured in solutions with varying Ca2+ concentrations, was shifted to the left by NZ-105. The relation between [Ca2+]i and tension measured in tetanic contraction was also shifted to the left by NZ-105. These results suggest that the inhibitory effect of NZ-105 on contraction in mammalian cardiac muscle is curtailed by an increase in Ca sensitivity of the contractile elements.