Sarcoplasmic reticulum proteins in heart failure

Abstract

Altered calcium homeostasis may play a key role in the pathophysiology of human heart failure. Levels of sarcoplasmic reticulum (SR) proteins and sarcolemmal Na(+)-Ca2+ exchanger were analyzed by Western blot in failing and nonfailing human myocardium and related to myocardial function. Levels of the SR calcium release channel and of calcium storage proteins (calsequestrin and calreticulin) were not different in nonfailing and failing hearts. However, proteins involved in calcium removal were significantly altered in the failing human heart: (1) SR-Ca(2+)-ATPase levels and the ratio of SR-Ca(2+)-ATPase to its inhibitory protein phospholamban were significantly decreased, and (2) Na(+)-Ca2+ exchanger levels and the ratio of Na(+)-Ca2+ exchanger to SR-Ca(2+)-ATPase were significantly increased. SR-Ca(2+)-ATPase levels were closely correlated to systolic function as evaluated by frequency potentiation of contractile force. The frequency-dependent rise of diastolic force was inversely correlated with protein levels of Na(+)-Ca2+ exchanger. These findings indicate that altered expression of SR-Ca(2+)-ATPase and Na(+)-Ca2+ exchanger is relevant for altered systolic and diastolic function in human heart failure.