Similarities and Contrasts in Ryanodine Receptor Localization and Function in Osteoclasts and Striated Muscle Cells

doi:10.1196/annals.1402.064

This review compares ryanodine receptor (RyR)-mediated Ca²⁺signaling processes in muscle and osteoclast cells. In muscle,RyR-mediated release of an intracellularly stored, sarcoplasmicreticular (SR), Ca²⁺ is triggered by voltage-sensitive dihydropyridinereceptor (DHPR)-L-type Ca²⁺ channels either through an allostericcoupling 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⁺-inducedSR Ca²⁺ release with cardiac muscle additionally showing a storeoverload-induced Ca²⁺ release (SOICR) driven by SR luminal Ca²⁺under some pathological conditions. Osteoclasts similarly showcytosolic Ca²⁺ elevations driven by release of intracellularCa²⁺ stores that culminate in motile activity in turn modifyingbone resorptive activity. However, such triggering is controlledby ambient Ca²⁺ rather than membrane potential with featuresstrongly suggestive of control by a surface membrane Ca²⁺ receptor.Yet common actions of the RyR-specific agents perchlorate, dantroleneNa, ryanodine, caffeine, adenosine 3',5'-cyclic diphosphateribose (cADPr) and ruthenium red implicate RyR in signalingin all these cell types. These findings were reconciled by reportsconfirming and uniquely localizing a cell surface rather thanmicrosomal osteoclastic RyR that might itself detect ambientCa²⁺ possibly through its otherwise intraluminal positionedlow-affinity Ca²⁺-binding site in parallel with the SOICR mechanismin cardiac muscle. Such a mechanism could interact with otherosteoclast processes transferring Ca²⁺ between cytosol, intracellularstores and extracellular space and be integrated with systemicprocesses regulating Ca²⁺ homeostasis.

Part II. Formation, Function, and Fate of Bone Cells