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. This evidence concerns the gene RYR2 and atrial fibrillation.