The RyR2-R420Q mutation increased late calcium sparks and inward sodium/calcium exchange current, resulting in action potential prolongation and early afterdepolarizations in a murine model of CPVT.
BACKGROUND: leak during systole disrupts repolarization in a transgenic mouse model of CPVT. METHODS: Electrocardiograms were recorded in patients with RyR2-R420Q CPVT mutation (R420Q). Experiments were performed on control and R420Q knock-in mouse hearts and ventricular myocytes. RESULTS: sparks (LCS). AP voltage clamp electrophysiology experiments, analysis of LCS recovery, and computer simulations of hyperactive RyR2 supported a mechanism involving increased RyR2 sensitivity and/or reduced refractoriness that increased LCS frequency and inward sodium/calcium exchange current, resulting in AP prolongation and EADs. CONCLUSIONS: -mediated AP lengthening and EADs may contribute to proarrhythmic behaviour in CPVT caused by gain-of-function R420Q mutation. Loss of repolarization reserve is not specifically targeted by CPVT therapies but could be an opportunity for therapeutic intervention.
Zissimopoulos et al. (Thu,) conducted a other in Catecholaminergic polymorphic ventricular tachycardia (CPVT). RyR2-R420Q mutation vs. Control was evaluated on Action potential prolongation and early afterdepolarizations. The RyR2-R420Q mutation increased late calcium sparks and inward sodium/calcium exchange current, resulting in action potential prolongation and early afterdepolarizations in a murine model of CPVT.