These data suggest that, under conditions of increased CaMKII-mediated RyR2 phosphorylation and tissue abnormality in the atria, amplification of the altered RyR2 activation and subsequent diastolic SR Ca2+ leakage enhance the susceptibility to pacing-induced AF in the BO group (Fig. 5), as in the case of ventricular arrhythmia in mice with R176Q cardiac RyR2 mutations50,51. The gene discussed is CAMK2G; the disease is atrial fibrillation.