Title: Dyssynchrony of Ca2+ release from the sarcoplasmic reticulum as subcellular mechanism of cardiac contractile dysfunction
Authors: Heinzel, Frank R
Macquaide, Niall
Biesmans, Liesbeth
Sipido, Karin # ×
Issue Date: Mar-2011
Publisher: Academic Press
Series Title: Journal of Molecular and Cellular Cardiology vol:50 issue:3 pages:390-400
Abstract: 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 Ca2+ release. The cytosolic [Ca2+] transient triggered by depolarization-induced Ca2+ influx is the result of a gradable and robust high gain process, Ca2+-induced Ca2+ release (CICR), which integrates subcellular localized Ca2+ 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 Ca2+ channels, the sarcoplasmic Ca2+ release channel or ryanodine receptor, RyR, their intracellular arrangement in close proximity in couplons and the loss oft-tubules. Dyssynchrony at the subcellular level translates in a reduction of the overall gain of OCR at the cellular level and forms an important determinant of myocyte contractility in heart failure. (C) 2010 Elsevier Ltd. All rights reserved.
ISSN: 0022-2828
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Experimental Cardiology
× corresponding author
# (joint) last author

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