Abnormalities of Calcium Cycling in the Hypertrophied and Failing Heart

Autor: Jutta Weisser, Valentino Piacentino, Steven R. Houser
Rok vydání: 2000
Předmět:
Zdroj: Journal of Molecular and Cellular Cardiology. 32:1595-1607
ISSN: 0022-2828
DOI: 10.1006/jmcc.2000.1206
Popis: 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 (Ca(2+)) regulation is primarily responsible for the depressed contractility of the failing heart. The review points out that Ca(2+)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 Ca(2+)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 Ca(2+)channels, Ca(2+)transport proteins [sarcoplasmic reticulum Ca(2+)ATPase (SERCA2), phospholamban (PLB), Na(+)/Ca(2+) exchanger (NCX)] and Ca(2+) release channels (RYR) in excitation-contraction coupling and Ca(2+)release and uptake by the sarcoplasmic reticulum (SR) are reviewed. These observations support our hypotheses that (i) defective Ca(2+)regulation involves multiple molecules and processes, not one molecule, (ii) the initiation and progression of CHF inolves defective Ca(2+)regulation, and (iii) prevention or correction of Ca(2+)regulatory defects in the early stages of cardiac diseases can delay or prevent the onset of CHF.
Databáze: OpenAIRE
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