Furthermore, western blot revealed a significant increase in the oxidation status of RyR2 immunoprecipitated from diseased VMs (Fig. 8c, d), supporting the hypothesis that increased RyR2 activity in CPVT is partially modulated by leak-induced mito-ROS, as in rat VMs with a caffeine-induced increase in RyR2 activity (Figs. 2, 3). Here, RYR2 is linked to catecholaminergic polymorphic ventricular tachycardia.