Heterogeneity of Ryanodine Receptor Dysfunction in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia

Abstract

The mutation RyR2-V2475F is phenotypically strong among other CPVT mutations and produces heterogeneous mechanisms of RyR2 dysfunction. In living mice, this mutation appears too severe to be harbored in all RyR2 channels but remains undetected under basal conditions if expressed at relatively low levels. β-adrenergic stimulation breaks the delicate Ca(2+) equilibrium of RyR2-V2475F(+/-) hearts and triggers life-threatening arrhythmias.