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Journal Articles Frontiers in Physiology Year : 2021

RyR2 and Calcium Release in Heart Failure


Heart Failure (HF) is defined as the inability of the heart to efficiently pump out enough blood to maintain the body's needs, first at exercise and then also at rest. Alterations in Ca 2+ handling contributes to the diminished contraction and relaxation of the failing heart. While most Ca 2+ handling protein expression and/or function has been shown to be altered in many models of experimental HF, in this review, we focus in the sarcoplasmic reticulum (SR) Ca 2+ release channel, the type 2 ryanodine receptor (RyR2). Various modifications of this channel inducing alterations in its function have been reported. The first was the fact that RyR2 is less responsive to activation by Ca 2+ entry through the L-Type calcium channel, which is the functional result of an ultrastructural remodeling of the ventricular cardiomyocyte, with fewer and disorganized transverse (T) tubules. HF is associated with an elevated sympathetic tone and in an oxidant environment. In this line, enhanced RyR2 phosphorylation and oxidation have been shown in human and experimental HF. After several controversies, it is now generally accepted that phosphorylation of RyR2 at the Calmodulin Kinase II site (S2814) is involved in both the depressed contractile function and the enhanced arrhythmic susceptibility of the failing heart. Diminished expression of the FK506 binding protein, FKBP12.6, may also contribute. While these alterations have been mostly studied in the left ventricle of HF with reduced ejection fraction, recent studies are looking at HF with preserved ejection fraction. Moreover, alterations in the RyR2 in HF may also contribute to supraventricular defects associated with HF such as sinus node dysfunction and atrial fibrillation.
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inserm-03608907 , version 1 (15-03-2022)



Ana Maria Gómez, Jean-Pierre Benitah, Romain Perrier, Jean-Jacques Mercadier, Laetitia Pereira, et al.. RyR2 and Calcium Release in Heart Failure. Frontiers in Physiology, 2021, 12, pp.734210. ⟨10.3389/fphys.2021.734210⟩. ⟨inserm-03608907⟩
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