The inhibitory effects of the novel calcium antagonist Goe 5438 on calcium-dependent processes of excitation and contraction of single cardiomyocytes.

The calcium-antagonistic properties of the novel compound Goe 5438 have been studied in single cardiomyocytes from embryonic (chicken) and adult (guinea-pig) ventricles, in part in comparison with the inhibitory effects of the 1,4-dihydropyridine calcium antagonist nimodipine. Both substances block spontaneous action potentials and contractions of embryonic heart cells at about 0.1 mumol/l. In collagenase-dispersed ventricular cardiomyocytes of guinea-pigs, stereospecific inhibition of the slow calcium current (ICa) by Goe 5438 was observed at 10 mumol/l by means of voltage-clamp experiments. The (+)-enantiomer of Goe 5438 elicited a stronger inhibition of the slow inward current than the (-)-enantiomer. The frequency dependence of the inhibitory effect of Goe 5438 as well as that of nimodipine could be shown to be negligible in measurements of ICa and contractions, whereas the inhibitory influence of verapamil, verified in the same experimental arrangement, exhibited a distinct frequency dependence. With respect to a possible potential dependence of the inhibitory effect of Goe 5438 and nimodipine, it could be shown that a hyperpolarization during the course of application of either calcium antagonist produced recovery of the calcium-dependent excitation neither in adult nor in embryonic cells. In adult cardiomyocytes, the dependence of ICa on the membrane potential was not altered by Goe 5438. It is concluded that the mode of action of Goe 5438 resembles that of 1,4-dihydropyridine calcium antagonists.