Checking your SOCCs and feet: the molecular mechanisms of Ca2+ entry in skeletal muscle

It has long been known that skeletal muscle contraction persists in the absence of extracellular Ca2+. Nevertheless, recent evidence indicates that multiple distinct Ca2+ entry pathways exist in skeletal muscle: one active at negative potentials that requires store depletion (store-operated calcium entry or SOCE) and a second that is independent of store depletion and is activated by depolarization (excitation-coupled calcium entry or ECCE). This review highlights recent findings regarding the molecular identity, subcellular localization, and inter-relationship between SOCE and ECCE in skeletal muscle. The respective roles of ryanodine receptors (RyRs), dihydropyridine receptors (DHPRs), inositol-1,4,5-trisphosphate receptors (IP(3)Rs), canonical transient receptor potential channels (TRPCs), STIM1 Ca2+ sensor proteins, and Orai1 Ca2+ permeable channels in mediating SOCE and ECCE in skeletal muscle are discussed. Differences between SOCE and ECCE in skeletal muscle with Ca2+ entry mechanisms in non-excitable cells are also reviewed. Finally, potential physiological roles for SOCE and ECCE in skeletal muscle development and function, as well as other currently unanswered questions and controversies in the field are also considered.