Altered Ca2+ sparks in aging skeletal and cardiac muscle

Ca²⁺ sparks are the fundamental units that comprise Ca²⁺-induced Ca²⁺ release (CICR) in striated muscle cells. In cardiac muscle, spontaneous Ca²⁺ sparks underlie the rhythmic CICR activity during heart contraction. In skeletal muscle, Ca²⁺ sparks remain quiescent during the resting state and are activated in a plastic fashion to accommodate various levels of stress. With aging, the plastic Ca²⁺ spark signal becomes static in skeletal muscle, whereas loss of CICR control leads to leaky Ca²⁺ spark activity in aged cardiomyocytes. Ca²⁺ spark responses reflect the integrated function of the intracellular Ca²⁺ regulatory machinery centered around the triad or dyad junctional complexes of striated muscles, which harbor the principal molecular players of excitation-contraction coupling. This review highlights the contribution of age-related modification of the Ca²⁺ release machinery and the effect of membrane structure and membrane cross-talk on the altered Ca²⁺ spark signaling during aging of striated muscles.