RYR2 and catecholaminergic polymorphic ventricular tachycardia: The RyR2-A4860G loss-of-function mutation thus reveals novel mechanisms of arrhythmogenesis in CPVT: first, mutant RyR2 channels decrease the peak of Ca2+ release during systole and thus impair L-type Ca2+ channel inactivation (faulty retroactive Ca2+ release→AP feedback), both of which gradually overload the SR.