Unchanged Protein Levels of SERCA II and Phospholamban but Reduced Ca2+ Uptake and Ca2+-ATPase Activity of Cardiac Sarcoplasmic Reticulum From Dilated Cardiomyopathy Patients Compared With Patients With Nonfailing Hearts

Background The aim of the present study was to investigate whether Ca2+ uptake into the sarcoplasmic reticulum (SR) is altered in failing human myocardium resulting from dilated cardiomyopathy. Methods and Results Ca2+-ATPase (SERCA II) activity and Ca2+-dependent 45Ca2+ uptake (oxalate supported, steady state) in isolated vesicles from the SR (VSR) and in crude membrane preparations (CSR) (free Ca2+, 0.01 to 100 μmol/L) from nonfailing (donor hearts, n=13) and terminally failing (heart transplants, dilated cardiomyopathy, n=17) human myocardium were studied. In the same hearts, protein levels (Western blot analysis) and mRNA levels (Northern blot analysis) of SERCA II and phospholamban were measured. Increasing concentrations of Ca2+ were followed by an increased Ca2+-ATPase activity and Ca2+ uptake. Ca2+ uptake activity and Ca2+-ATPase activity in CSR preparations from failing myocardium were significantly reduced compared with nonfailing hearts (Ca2+-ATPase, 163±8 and 125±7 nmol ATP/mg protein per minu...