The Ryanodine Receptor Leak: Its Role in the Development of Heart Failure
Keywords:Ryanodine receptor, heart failure, cardiac arrhythmias, novel therapeutic strategies
The cardiac ryanodine receptor-Ca2+ release channel (RyR2) is an essential sarcoplasmic reticulum (SR) transmembrane protein that plays a central role in excitation-contraction coupling in cardiomyocytes. Aberrant spontaneous, diastolic Ca2+ leak from the SR due to dysfunctional RyR2 is the mechanism underlying contractile and relaxation dysfunctions in heart failure.
Several potential mechanisms have been proposed to explain the dysfunctional RyR2 in heart failure including overphosphorylation status of RyR2, altered RyR2 regulation and perturbed RyR2 intra/intermolecular interactions.Novel therapeutic strategies that enhance myocyte Ca2+ homeostasis could prevent and reverse adverse cardiac remodeling and improve clinical outcomes in patients with heart failure.
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