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 st udies that hare addressed the idea that alterations of intracellular calciu m (Ca2+) regulation is primarily responsible for the depressed contractilit y of the failing heart. The review points out that Ca2+ transients and cont raction are similar in non-failing and failing myocytes at very slow freque ncies of stimulation land other low stress environments). Faster pacing rat es, high Ca2+ and beta-adrenergic stimulation reveal large reductions in co ntractile reserve in failing myocytes. The underlying cellular basis of the se defects is then considered. Studies showing changes in the abundance of L-type Ca2+ channels, Ca2+ transport proteins [sarcoplasmic reticulum Ca2ATPase (SERCA2), phospholamban (PLB), Na+/Ca2+ exchanger (NCX] and Ca2+ rel ease 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 multipl e molecules and processes, not one molecule, (ii) the initiation and progre ssion of CHF involves defective Ca2+ regulation, and (iii) prevention or co rrection of Ca2+ regulatory defects in the early stages of cardiac diseases can delay or prevent the onset of CHF. (C) 2000 Academic Press.