RYR2 and heart failure: The beneficial roles of Serca2a and RyR2 expression in cardiomyocyte calcium handling during cardiac hypertrophy and heart failure have been well established 42-44: while RyR2 activity results in rapid Ca2+-release from the sarcoplasmic reticulum (SR) and transient increase of intracellular Ca2+ concentration to trigger cell contraction, Serca2a removes Ca2+ from the sarcoplasm through Ca2+ reuptake into the SR to ensure cell relaxation.