Abnormalities of Calcium Cycling in the Hypertrophied and Failing Heart

S. R. Houser, V. Piacentino III and J. Weisser. Abnormalities of Calcium Cycling in the Hypertrophied and Failing Heart. Journal of Molecular and Cellular Cardiology (2000) 32, 1595–1607. Progressive deterioration of cardiac contractility is a central feature of congestive heart failure (CHF) in humans. In this report we review those studies that have 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 (and other low stress environments). Faster pacing rates, high Ca2+and β-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 inolves 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.