Effects of Bay Y5959 on Ca2+ currents and intracellular Ca2+ in cells thathave 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 Ca2+ currents and intracellular Ca2+ tran sients in epicardial cells from noninfarcted hearts (NZs) and surviving cel ls from the epicardial border zone of 5-day infarcted canine hearts (IZs). We determined the effects of Bay Y5959 on the L-type Ca2+ current by using single cells and a whole-cell voltage-clamp approach. To elucidate the effe cts of Bay Y5959 on the amplitude and time course of the spatially averaged intracellular Ca2+ transient (CaiT), myocytes from the two cell groups wer e loaded and studied by using the Ca2+-sensitive indicator fura-2/AM. Bay Y 5959 increased the amplitude of the L-type Ca2+ 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 acceler ated the CaiT time course in IZs, particularly at the faster pacing-cycle l ength. We suggest that the Bay Y5959 effect to restore L-type Ca2+ currents in IZs contributes to its observed antiarrhythmic effects during the reent rant ventricular tachycardias that are known to occur in the epicardial bor der zone of the infarcted heart.