title: Abnormalities of calcium cycling in the hypertrophied and failing heart.
abstract: 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.
authors.affiliation: Cardiovascular Research Group, Molecular and Cellular Cardiology Laboratories, Department of Physiology, 3400 North Broad Street, Philadelphia, PA 19140, USA. srhouser@unix.temple.edu
authors.forename: S R
authors.initials: SR
authors.lastname: Houser
authors.forename: V
authors.initials: V
authors.lastname: Piacentino
authors.forename: J
authors.initials: J
authors.lastname: Weisser
mesh_terms: D002118:Calcium / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002118:Calcium