title: Dyssynchrony of Ca2+ release from the sarcoplasmic reticulum as subcellular mechanism of cardiac contractile dysfunction.
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 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.
authors.affiliation: Division of Cardiology, Medical University of Graz, Austria.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Heinzel
authors.forename: Niall
authors.initials: N
authors.lastname: MacQuaide
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Biesmans
authors.forename: Karin
authors.initials: K
authors.lastname: Sipido
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism* / Q000502:physiology*
chemical_list: D002118:Calcium