UNALTERED RYANODINE RECEPTOR PROTEIN-LEVELS IN ISCHEMIC CARDIOMYOPATHY

Previous studies on sarcoplasmic reticulum calcium release channel (ry anodine receptor) demonstrated that protein levels are unchanged in my ocardium from hearts with end-stage failing dilated cardiomyopathy. In ischemic cardiomyopathy, ryanodine receptor mRNA levels were shown to be decreased but no data on protein levels are available. Accordingly , protein levels of ryanodine receptor, calsequestrin, and sarcoplasmi c reticulum calcium-ATPase (SR-Ca2+-ATPase) were measured by Western b lot analysis in nonfailing human myocardium (n = 7) and in end-stage f ailing myocardium due to ischemic cardiomyopathy (n = 14). Protein lev els of calsequestrin which is the major sarcoplasmic reticulum calcium storage protein were similar in nonfailing myocardium and in myocardi um from end-stage failing hearts with ischemic cardiomyopathy. Ryanodi ne receptor protein levels, normalized to total protein or calsequestr in were also unchanged in ischemic cardiomyopathy. In contrast, protei n levels of SR-Ca2+-ATPase normalized to total protein or calsequestri n were decreased by 31 and 30%, respectively (p < 0.05). The data indi cate that (1) sarcoplasmic reticulum calcium uptake sites are decrease d relative to the release sites in ischemic cardiomyopathy, and (2) al terations of sarcoplasmic proteins are similar in ischemic and dilated cardiomyopathy.