Abnormalities in CaiHandling in Myocytes that Survive in the Infarcted Heart are not just due to Alterations in Repolarization

Studies from our laboratory have defined alterations in Caihandling in the non-dialyzed subepicardial cells that have survived in the 5 day infarcted heart (IZs). To determine whether changes in the action potential profile contributed to the observed Caichanges we have used a combined voltage clamp/epifluorescent technique to determine and compare changes in fura 2 ratios in IZs compared to those of epicardial cells from the non-infarcted canine hearts (NZs). We found that Caichanges in voltage clamped IZs persisted. In NZs, Caitransients showed the expected voltage dependence while IZs did not. To determine whether altered NaCa exchanger activity contributed to the observed changes in Caiin IZs, we measured NaCa exchanger Ca2+fluxes (reverse and forward mode) and ionic currents in both cell types and under different Nailoads (10 and 20 m ). We found that there were no significant differences in resting, peak or magnitude of fura 2 ratio changes or in outward current densities between NZs and IZs even under the different Nailoads. Thus, we suggest that chronic up- or downregulation of the NaCa exchanger protein does not underlie observed Caichanges in IZs. Additionally, Ca2+released with paced voltage steps represented 79% of that released by caffeine in NZs while, in IZs, caffeine releasable Ca2+was equivalent to that released with step depolarization. Thus, abnormalities in Caihandling in IZs appear not to arise secondarily to changes in action potential configuration nor do they appear to be due to disease-induced alteations in NaCa exchanger function.