Mutations in RYR2 can increase the probability of channel open during diastole, resulting in excess diastolic SR Ca2+ release, and the increased SR Ca2+ leak during diastole can increase the frequency of spontaneous Ca2+ sparks, resulting in an untimely depolarizing inward current that triggers delayed after depolarization and ventricular arrhythmia or atrial fibrillation.41 This evidence concerns the gene RYR2 and atrial fibrillation.