Ca2+ release refractoriness, measured using the ratio of the second:first Ca2+ spark occurring from the same CRU using a chemical modification of RyR2 with low concentration ryanodine [104], was reduced in a transgenic mouse model of the GoF CPVT-causing RyR2-R420Q+/− mutation under both basal and isoproterenol stimulation, indicating increased CICR sensitivity [105]. This evidence concerns the gene RYR2 and catecholaminergic polymorphic ventricular tachycardia.