Effects of Bay Y5959 on Ca2+ Currents and Intracellular Ca2+ in Cells That Have Survived in the Epicardial Border of the Infarcted Canine Heart

We determined and compared the effects of the dihydropyridine agonist, Bay Y5959, on the amplitude of L-type Ca currents and intracellular Ca transients in epicardial cells from noninfarcted hearts (NZs) and surviving cells from the epicardial border zone of 5-day infarcted canine hearts (IZs). We determined the effects of Bay Y5959 on the L-type Ca current by using single cells and a whole-cell voltage-clamp approach. To elucidate the effects of Bay Y5959 on the amplitude and time course of the spatially averaged intracellular Ca transient (CaiT), myocytes from the two cell groups were loaded and studied by using the Ca-sensitive indicator fura-2/AM. Bay Y5959 increased the amplitude of the L-type Ca current in both cell groups, but peak amplitude in NZs was always greater than that in IZs. Bay Y5959 also increased CaiT amplitude in both NZs and IZs and significantly accelerated the CaiT time course in IZs, particularly at the faster pacing-cycle length. We suggest that the Bay Y5959 effect to restore L-type Ca currents in IZs contributes to its observed antiarrhythmic effects during the reentrant ventricular tachycardias that are known to occur in the epicardial border zone of the infarcted heart.