Labedipinedilol-A, a novel dihydropyridine-type calcium antagonist with appla/beta-adrenocep-tor blocking properties, has been reported to produce a cardioprotective effect against ischemia reperfusion injury in rats. We investigated the protective effects of labedipinedilol-A on ouabain-induced tonotropy and arrhythmias in isolated whole atria, and using patch-clamp techniques to study the underlying mechanism of its antiarrhythmic activity on isolated cardiac myocytes. Labedipinedilol-A (10 muM) suppressed the tonotropic effect of ouabain significantly and prolonged the onset time of extra-systole (arrhythmia) induced by ouabain in isolate atria. In the voltage-clamp study, labedipinedilol-A (1-100 muM) reduced the peak amplitude of sodium inward current (I_V) and L-type calcium current (I_(Ca-L))/ and shifted the current-voltage (I-V) curve upward in a concentration-dependent manner. In contrast, the addition of labedipinedilol-A increased transient outward potassium current (I_(to)) and inward rectifier potassium current (I_(K1)) significantly. Labedipinedilol-A (10 muM) also effectively depressed the isoproter-enol-induced increase in the Ca~(2+) current. These results show that labedipinedilol-A blocks I_(Ca-L) and I_(Na) and increases I_(to) and I_(K1). These findings indicate that labedipinedilol-A produces direct cardiac action, probably due to the inhibition of cardiac Na~+ and Ca~(2+) channels. Our results suggest that labedipinedilol-A may reduce the membrane conduction through inhibition of ionic channels which decrease ouabain-induced arrhythmia.
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