Dyssynchrony of Ca2+ release from the sarcoplasmic reticulum as subcellular mechanism of cardiac contractile dysfunction

Heinzel, F. R., MacQuaide, N. , Biesmans, L. and Sipido, K. (2011) Dyssynchrony of Ca2+ release from the sarcoplasmic reticulum as subcellular mechanism of cardiac contractile dysfunction. Journal of Molecular and Cellular Cardiology, 50(3), pp. 390-400. (doi: 10.1016/j.yjmcc.2010.11.008) (PMID:21075114)

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Cardiac contractile function depends on coordinated electrical activation throughout the heart. Dyssynchronous electrical activation of the ventricles has been shown to contribute to contractile dysfunction in heart failure, and resynchronization therapy has emerged as a therapeutic concept. At the cellular level, coupling of membrane excitation to myofilament contraction is facilitated by highly organized intracellular structures which coordinate Ca(2+) release. The cytosolic [Ca(2+)] transient triggered by depolarization-induced Ca(2+) influx is the result of a gradable and robust high gain process, Ca(2+)-induced Ca(2+) release (CICR), which integrates subcellular localized Ca(2+) release events. Lack of synchronization of these localized release events can contribute to contractile dysfunction in myocardial hypertrophy and heart failure. Different underlying mechanisms relate to functional and structural changes in sarcolemmal Ca(2+) channels, the sarcoplasmic Ca(2+) release channel or ryanodine receptor, RyR, their intracellular arrangement in close proximity in couplons and the loss of t-tubules. Dyssynchrony at the subcellular level translates in a reduction of the overall gain of CICR at the cellular level and forms an important determinant of myocyte contractility in heart failure.

Item Type:Articles
Glasgow Author(s) Enlighten ID:MacQuaide, Dr Niall
Authors: Heinzel, F. R., MacQuaide, N., Biesmans, L., and Sipido, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Molecular and Cellular Cardiology
ISSN (Online):1095-8584

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