RYR2 and catecholaminergic polymorphic ventricular tachycardia: While flecainide-induced effects on RyR2 have been reported in permeabilized ARVM (Hilliard et al., 2010), the level of drug required was higher than the peak plasma concentration in patients (Mano et al., 2015), or that needed to modulate RyR2 in cells from CPVT mice (Galimberti and Knollmann, 2011; Gomez-Hurtado et al., 2015).