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(i)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(i)changes 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 Ca(i)changes in voltage clamped IZs persisted. In NZs, Ca(i)transients showed the expected voltage dependence while IZs did not. To determine whether altered NaCa exchanger activity contributed to the observed changes in Ca(i)in IZs, we measured NaCa exchanger Ca(2+)fluxes (reverse and forward mode) and ionic currents in both cell types and under different Na(i)loads (10 and 20 m 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 Na(i)loads. Thus, we suggest that chronic up- or downregulation of the NaCa exchanger protein does not underlie observed Ca(i)changes in IZs. Additionally, Ca(2+)released with paced voltage steps represented 79% of that released by caffeine in NZs while, in IZs, caffeine releasable Ca(2+)was equivalent to that released with step depolarization. Thus, abnormalities in Ca(i)handling 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. Copyright 2000 Academic Press.