0000000000347280
AUTHOR
Olivier Villejoubert
Mechanism of Sinoatrial Node Dysfunction in a RyR 2 R420Q Mouse Model Ofcatecholaminergic Polymorphic Ventricular Tachycardia
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disease characterized by stress-induced syncope and/or sudden death in young individuals with structurally normal heart. More than 150 mutations located in the cardiac Ca2+ release channel (type-2 ryanodine receptor, RyR2) gene are related to CPVT. Besides ventricular tachycardia (VT) under stress, sinoatrial node (SAN) dysfunction is frequently observed in CPVT patients. However, the cellular mechanisms remain underexplored. We created a KI mice model bearing a mutation in the N-terminal portion of the RyR2 found in a CPVT family, RyR2(R420Q). ECGs were recorded in KI and WT littermates in resting condition and after…
Impaired Binding to Junctophilin-2 and Nanostructural Alteration in CPVT Mutation
Rationale: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare disease, manifested by syncope or sudden death in children or young adults under stress conditions. Mutations in the Ca 2+ release channel/RyR2 (type 2 ryanodine receptor) gene account for about 60% of the identified mutations. Recently, we found and described a mutation in RyR2 N-terminal domain, RyR2 R420Q . Objective: To determine the arrhythmogenic mechanisms of this mutation. Methods and Results: Ventricular tachycardias under stress conditions were observed in both patients with catecholaminergic polymorphic ventricular tachycardia and knock-in mice. During action potential recording (by patch-clamp in …