Electrophysiological Properties of SD-3211, a Novel Putative Ca2+ Antagonist, in Isolated Guinea Pig and Rabbit Hearts

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Abstract
The cardiac effects of SD-3211, a novel nondihydropyridine type of Ca2+ antagonist, were examined in isolated guinea pig and rabbit hearts using an electrophysiological technique. SD-3211 (10 -6-10-5M) shortened the action potential duration of guinea pig papillary muscles in a concentration-dependent manner without affecting the resting potential or the maximum upstroke velocity (JOURNAL/jcph/04.02/00005344-199011000-00012/ENTITY_OV0622/v/2017-07-28T025500Z/r/image-pngmax). The JOURNAL/jcph/04.02/00005344-199011000-00012/ENTITY_OV0622/v/2017-07-28T025500Z/r/image-pngmax of slow responses induced by high extracellular K+ and isoproterenol was inhibited by SD-3211 at concentrations of >10-6M. Elevation of extracellular Ca2+ by 2 m M reversed this inhibited response. The inhibitory effect of SD-3211 on the slow response was enhanced as the stimulation frequency was increased. In Langendorff-perfused rabbit hearts electrically driven at 2.0 Hz, SD-3211 (10 -8-10-6M) produced a concentration-dependent prolongation of the atrium- His bundle conduction time (A-H interval) as well as a reduction in the developed tension of ventricular muscle, whereas SD-3211 did not affect the His bundle-ventricular conduction time (A-H interval) significantly. The potency of SD-3211 in A-H prolongation was greater than those of diltiazem and bepridil, but weaker than those of nicardipine, nifedipine, and verapamil. The effect of SD-3211 on the A-H interval was more pronounced at higher stimulation frequencies. SD-3211 was intermediate between nicardipine, nifedipine, and verapamil in its intensity of frequency- dependent effects on the A-H interval. These results suggest that SD-3211 has a preferential and frequency- dependent inhibitory action on cardiac slow Ca2 + channels