RYR2 and catecholaminergic polymorphic ventricular tachycardia: ,42 Enhancement of RyR2 activity with caffeine43,44 or CPVT gain-of-function mutations (e.g. R4496C)20,45,46 result in higher frequency of spontaneous Ca2+ transients and lower Ca2+ store content in both HEK293/RyR2 cells and cardiac myocytes.