RYR2 and heart failure: However, when heart failure occurs, on the one hand, due to the reduction of SERCA2a function, the increase of RyR leakage, the increase of Na+-Ca2+ exchange (NCX) function competing with SERCA2a for Ca2+, the Ca2+ released by SR after LTCC activation is reduced, which can not meet the transient of calcium ions in cardiomyocytes, resulting in the significant decrease of myocardial contractility (66).