Similarities and Contrasts in Ryanodine Receptor Localization and Function in Osteoclasts and Striated Muscle Cells
This review compares ryanodine receptor (RyR)-mediated Ca2+ signaling processes in muscle and osteoclast cells. In muscle, RyR-mediated release of an intracellularly stored, sarcoplasmic reticular (SR), Ca2+ is triggered by voltage-sensitive dihydropyridine receptor (DHPR)-L-type Ca2+ channels either through an allosteric coupling with the RyR in skeletal muscle or a Ca2+-induced Ca2+ release initiated by extracellular Ca2+ entry in cardiac muscle. Both cell subtypes are nevertheless capable of Ca2+-induced SR Ca2+ release with cardiac muscle additionally showing a store overload-induced Ca2+ release (SOICR) driven by SR luminal Ca2+ under some pathological conditions. Osteoclasts similarly show cytosolic Ca2+ elevations driven by release of intracellular Ca2+ stores that culminate in motile activity in turn modifying bone resorptive activity. However, such triggering is controlled by ambient Ca2+ rather than membrane potential with features strongly suggestive of control by a surface membrane Ca2+ receptor. Yet common actions of the RyR-specific agents perchlorate, dantrolene Na, ryanodine, caffeine, adenosine 3?,5?-cyclic diphosphate ribose (cADPr) and ruthenium red implicate RyR in signaling in all these cell types. These findings were reconciled by reports confirming and uniquely localizing a cell surface rather than microsomal osteoclastic RyR that might itself detect ambient Ca2+ possibly through its otherwise intraluminal positioned low-affinity Ca2+-binding site in parallel with the SOICR mechanism in cardiac muscle. Such a mechanism could interact with other osteoclast processes transferring Ca2+ between cytosol, intracellular stores and extracellular space and be integrated with systemic processes regulating Ca2+ homeostasis
ryanodine receptor osteoclasts skeletal muscle cardiac muscle calcium