2015 Articles

Essential roles of intracellular calcium release channels in muscle, brain, metabolism, and aging

Santulli, Gaetano; Marks, Andrew R.

Calcium (Ca2+) release from intracellular stores controls numerous cellular processes, including cardiac and skeletal muscle contraction, synaptic transmission and metabolism. The ryanodine receptors (RyRs) and inositol 1,4,5--trisphosphate receptors (IP3Rs) are the majorCa2+ release channels (CRCs) on the endo/sarcoplasmic reticulum(ER/SR).RyR1 and RyR2 are the key isoforms in skeletal and cardiac muscle and are essential role in excitation--contraction(E--C) coupling. IP3R1 and IP3R2 are required for muscle and neuronal function. RyRs and IP3Rs comprise macromolecular signaling complexes that include modulatory proteins which regulate channel activity in response to extracellular signals resulting in intracellular Ca2+ release. This review focuses on the roles of CRCs in heart, skeletal muscle, brain, and aging.