Review Paper
Abnormalities of Calcium Cycling in the Hypertrophied and Failing Heart

https://doi.org/10.1006/jmcc.2000.1206Get rights and content

Abstract

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.

References (95)

  • MA Kirchberger et al.

    Adenosine 3:5-monophosphate-dependent protein kinase-catalyzed phosphorylation reaction and its relationship to calcium transport in cardiac sarcoplasmic reticulum

    J Biol Chem

    (1974)
  • HK Simmerman et al.

    Sequence analysis of phospholamban. Identification of phosphorylation sites and two major structural domains

    J Biol Chem

    (1986)
  • RH Schwinger et al.

    Reduced Ca2+-sensitivity of SERCA2a in failing human myocardium due to reduced serine-16 phospholamban phosphorylation

    J Mol Cell Cardiol

    (1999)
  • DM Bers et al.

    Can Ca2+entry via Na+–Ca2+exchange directly activate cardiac muscle contraction?

    J Mol Cell Cardiol

    (1988)
  • RP Rasmussen et al.

    Calcium antagonist binding sites in failing and nonfailing human ventricular myocardium

    Biochem Pharmacol

    (1990)
  • T Mewes et al.

    L-type calcium currents of human myocytes from ventricle of non-failing and failing hearts and from atrium

    J Mol Cell Cardiol

    (1994)
  • U Schmidt et al.

    Contribution of abnormal sarcoplasmic reticulum ATPase activity to systolic and diastolic dysfunction in human heart failure

    J Mol Cell Cardiol

    (1998)
  • DJ Beuckelmann et al.

    Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure

    Circulation

    (1992)
  • BA Bailey et al.

    Sarcoplasmic reticulum-related changes in cytosolic calcium in pressure-overload-induced feline LV hypertrophy

    Am J Physiol

    (1993)
  • Y Urabe et al.

    Cellular and ventricular contractile dysfunction in experimental canine mitral regurgitation

    Circ Res

    (1992)
  • SE Litwin et al.

    Enhanced Na+–Ca2+exchange in the infarcted heart. Implications for excitation-contraction coupling

    Circ Res

    (1997)
  • JM Capasso et al.

    Cytosolic calcium transients in myocytes isolated from rats with ischemic heart failure

    Am J Physiol

    (1993)
  • A Yao et al.

    Abnormal myocyte Ca2+homeostasis in rabbits with pacing-induced heart failure

    Am J Physiol

    (1998)
  • DA Hendrick et al.

    The pig as a model of tachycardia and dilated cardiomyopathy

    Lab Anim Sci

    (1990)
  • PG Volders et al.

    Cellular basis of biventricular hypertrophy and arrhythmogenesis in dogs with chronic complete atrioventricular block and acquired torsade de pointes

    Circulation

    (1998)
  • B O»Rourke et al.

    Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure, I: experimental studies

    Circ Res

    (1999)
  • LR Jones et al.

    Regulation of Ca2+signaling in transgenic mouse cardiac myocytes overexpressing calsequestrin

    J Clin Invest

    (1998)
  • SR Shorofsky et al.

    Cellular mechanisms of altered contractility in the hypertrophied heart: big hearts, big sparks

    Circ Res

    (1999)
  • E McCall et al.

    Ca2+flux, contractility, and excitation-contraction coupling in hypertrophic rat ventricular myocytes

    Am J Physiol

    (1998)
  • HB Nuss et al.

    Effect of duration of depolarization on contraction of normal and hypertrophied feline ventricular myocytes

    Cardiovasc Res

    (1994)
  • S Kääb et al.

    Ionic mechanism of action potential prolongation in ventricular myocytes from dogs with pacing-induced heart failure

    Circ Res

    (1996)
  • LS Maier et al.

    Effects of left ventricular hypertrophy on force and Ca2+handling in isolated rat myocardium

    Am J Physiol

    (1998)
  • M Inoko et al.

    Transition from compensatory hypertrophy to dilated, failing left ventricles in Dahl salt-sensitive rats

    Am J Physiol

    (1994)
  • CH Davies et al.

    Reduced contraction and altered frequency response of isolated ventricular myocytes from patients with heart failure

    Circulation

    (1995)
  • JK Gwathmey et al.

    Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure

    Circ Res

    (1987)
  • JP Morgan

    Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction

    N Engl J Med

    (1991)
  • K Nagata et al.

    Early changes in excitation-contraction coupling: transition from compensated hypertrophy to failure in Dahl salt-sensitive rat myocytes

    Cardiovasc Res

    (1998)
  • E Kiss et al.

    Differential changes in cardiac phospholamban and sarcoplasmic reticular Ca2+–ATPase protein levels. Effects on Ca2+transport and mechanics in compensated pressure-overload hypertrophy and congestive heart failure

    Circ Res

    (1995)
  • H Reuter et al.

    Calcium current and activation of contraction in ventricular myocardial fibers

    Science

    (1969)
  • JW Bassani et al.

    Fractional SR Ca2+release is regulated by trigger Ca2+and SR Ca2+content in cardiac myocytes

    Am J Physiol

    (1995)
  • B Pieske et al.

    Ca2+handling and sarcoplasmic reticulum Ca2+content in isolated failing and nonfailing human myocardium

    Circ Res

    (1999)
  • KR Sipido et al.

    Frequency dependence of Ca2+release from the sarcoplasmic reticulum in human ventricular myocytes from end-stage heart failure

    Cardiovasc Res

    (1998)
  • Bers, DM, Excitation-Contraction Coupling and Cardiac Contractile Force. 1991. Kluwer Academic Publishers, Dordrecht,...
  • RB Kleiman et al.

    Calcium currents in normal and hypertrophied isolated feline ventricular myocytes

    Am J of Physiol

    (1988)
  • R Mukherjee et al.

    Changes in L-type calcium channel abundance and function during the transition to pacing-induced congestive heart failure

    Cardiovasc Res

    (1998)
  • S Li et al.

    Calcium current and calcium transients are depressed in failing human ventricular myocytes and recover in patients supported with left ventricular assist devices. (Abstract)

    Circulation

    (1999)
  • AM Gomez et al.

    Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure

    Science

    (1997)
  • Cited by (288)

    View all citing articles on Scopus
    f1

    Please address all correspondence to: Steven R. Houser, Laura H. Carnell, Professor of Physiology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA. E-mail: [email protected]

    View full text