Schematic representation of changes in Type 2 Ryanodine receptors (RyR2) and related proteins in heart failure (HF). Left, represents Ca2+ handling in a cell from normal heart, and right, represents Ca2+ handling in a cell from a failing heart. 1) shows increased RyR2 activity represented by a wide open RyR2 due to post-translational modification by increased protein kinase A (PKA) and Ca2+/CaM-dependent protein kinase II (CaMKII) activity, reduced protein phosphatases (PP) 1 and PP 2A activity, reduced junctophilin 2 (JPH2) leading to abnormalities in T-tubule structure and increased oxidation by reactive oxygen species (ROS), 2) represents complex changes in L-type Ca2+ channel (LTCC) as discussed in the text, 3) represents reduced SR/ER Ca2+-ATPase (SERCA2a) activity and corresponding increased phospholamban (PLN) and Sarcolipin (SLN) activity, and 4) represents increased Na+/Ca2+ exchanger (NCX) activity, in heart failure. ↑ represents increase and ↓ represents decrease.