Skeletal muscle store-operated Ca²⁺ entry and STIM/Orai signaling in skeletal muscle

In skeletal muscle, Ca2+ release from intracellular stores triggers actomyosin cross-bridge formation to generate and modulate contractile force, but myocytes also use Ca2+ signaling as a way to sense and respond to changes in workload to alter gene expression and cellular metabolism. Here we have proposed store-operated Ca2+ entry (SOCE) as a mechanism by which Ca2+ signaling pathways are activated in order to respond to the changing demands of the myocyte. Abnormalities of store-operated Ca2+ influx may contribute to maladaptive muscle remodeling in multiple disease states. The importance of store-operated Ca2+ influx in muscle is confirmed in mice lacking STIM1 which die perinatally and in patients with mutations on STIM1 or Orai1 who exhibit a myopathy characterized by hypotonia. In this chapter, we consider the role of store-operated Ca2+ entry into skeletal muscle as a critical mediator of Ca2+ dependent gene expression and how alterations in Ca2+ influx may influence muscle development and disease.

Duke Scholars

Author Jonathan Andrew Stiber Medicine, Cardiology

Author Paul Brian Rosenberg Medicine, Cardiology