Fig. 4.

Relationships among disordered Ca²⁺ homeostasis, autophagy, necrosis and apoptosis in HF. It is generally accepted that depletion of SR Ca²⁺ stores, coupled with rises in cytosolic Ca²⁺, perturb EC coupling and elicit changes in cellular signaling events. Post-translational modifications (PTM) of RyR2 and reduced SERCA activity redistribute SR Ca²⁺ to the cytosol. Increased cytosolic Ca²⁺ also triggers pathways that contribute to cardiac muscle wasting. Activation of apoptotic pathways (e.g. calpains, caspases, or mPTP opening) has been extensively related to Ca²⁺ dysregulation, and there is some evidence pointing to altered autophagic signaling as well.