Mark Scoote*, Alan J. Williams*
Department of Cardiac Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Dovehouse Street,
London SW3 6LY, UK
Received 11 August 2004
Available online 21 August 2004

Abstract

Myocardial calcium signalling is a vital component of the normal physiological function of the heart. Key amongst the many roles calcium plays is its use as the primary signalling component of excitation–contraction coupling, the intracellular process that links cardiomyocyte depolarisation to contraction. Defective cellular calcium handling, due to abnormalities of the various components which mediate and control excitation–contraction coupling, is widely recognised as a significant patho-physiological event in the contractile dysfunction of the failing heart. In addition, similar defects also appear to be increasingly recognised as mediators of certain forms of cardiac arrhythmias. Such defects include single gene defects in excitation–contraction coupling components that lead to inherited sudden death arrhythmia syndromes. Alternatively, arrhythmogenesis occurring within the context of acquired cardiac disease, in particular heart failure, also appears to be highly dependent on abnormal calcium homeostasis. In this article we review the defects in cardiomyocyte calcium homeostasis that lead to particular pro-arrhythmogenic phenomena and discuss recent insights gained into a variety of inherited and acquired arrhythmia syndromes that appear to involve defective calcium signalling as a central component of their patho-physiology. Potential opportunities for new anti arrhythmic therapeutic strategies based on these recent insights are also discussed.

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