Abnormalities in Ca-i handling in myocytes that survive in the infarcted heart are not just due to alterations in repolarization

Studies from our laboratory have defined alterations in Ca, handling 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 Ca, changes we have used a combined voltage cla mp/epifluorescent technique to determine and compare changes in fura 2 rati os in IZs compared to those of epicardial cells from the noninfarcted canin e hearts (NZs). We found that Ca, changes in voltage clamped IZs persisted. In NZs, Ca, transients showed the expected voltage dependence while IZs di d not. To determine whether altered NaCa exchanger activity contributed to the observed changes in Ca, in IZs, we measured NaCa exchanger Ca2+ fluxes (reverse and forward mode) and ionic currents in both cell types and under different Na, loads (10 and 20 mM). We found that there were no significant differences in resting, peak or magnitude of fura 2 ratio changes or in ou tward current densities between NZs acid IZs even under the different Na, l oads. Thus, we suggest that chronic up- or downregulation of the NaCa excha nger protein does not underlie observed Ca, changes in IZs. Additionally, C a2+ released with paced voltage steps represented 79% of that released by c affeine in NZs while, in IZs, caffeine releasable Ca2+ was equivalent to th at released with step depolarization. Thus, abnormalities in Ca, handling i n IZs appear not to arise secondarily to changes in action potential config uration nor do they appear to be due to disease-induced alteations in NaCa exchanger function. (C) 2000 Academic Press.