Abnormalities of calcium cycling in the hypertrophied and failing heart

Progressive deterioration of cardiac contractility is a central feature of congestive heart failure (CHF) in humans. In this report we review those studies that hare addressed the idea that alterations of intracellular calcium (Ca2+) regulation is primarily responsible for the depressed contractility of the failing heart. The review points out that Ca2+ transients and contraction are similar in non-failing and failing myocytes at very slow frequencies of stimulation land other low stress environments). Faster pacing rates, high Ca2+ and beta-adrenergic stimulation reveal large reductions in contractile reserve in failing myocytes. The underlying cellular basis of these defects is then considered. Studies showing changes in the abundance of L-type Ca2+ channels, Ca2+ transport proteins [sarcoplasmic reticulum Ca2+ ATPase (SERCA2), phospholamban (PLB), Na+/Ca2+ exchanger (NCX] and Ca2+ release channels (RYR) in excitation-contraction coupling and Ca2+ release and uptake by the sarcoplasmic reticulum (SR) are reviewed, These observations support our hypotheses that (i) defective Ca2+ regulation involves multiple molecules and processes, not one molecule, (ii) the initiation and progression of CHF involves defective Ca2+ regulation, and (iii) prevention or correction of Ca2+ regulatory defects in the early stages of cardiac diseases can delay or prevent the onset of CHF. (C) 2000 Academic Press.