RYR2 and cardiac arrhythmia: Because the RyR2 is commonly dysfunctional in most settings where SERCA is less efficient in removing diastolic Ca2+, it is implied that increasing SR Ca2+ without addressing the increased opening probability of the RyR2 could result in an enhanced spark frequency and higher Ca2+ wave propagation, caused by RyR2 opening due to increased luminal Ca2+ sensibility, with subsequent arrhythmia development.