Similarities and contrasts in ryanodine receptor localization and function in osteoclasts and striated muscle cells.
This review compares ryanodine receptor (RyR)-mediated Ca(2+) signaling processes in muscle and osteoclast cells. In muscle, RyR-mediated release of an intracellularly stored, sarcoplasmic reticular (SR), Ca(2+) is triggered by voltage-sensitive dihydropyridine receptor (DHPR)-L-type Ca(2+) channels either through an allosteric coupling with the RyR in skeletal muscle or a Ca(2+)-induced Ca(2+) release initiated by extracellular Ca(2+) entry in cardiac muscle. Both cell subtypes are nevertheless capable of Ca(2+)-induced SR Ca(2+) release with cardiac muscle additionally showing a store overload-induced Ca(2+) release (SOICR) driven by SR luminal Ca(2+) under some pathological conditions. Osteoclasts similarly show cytosolic Ca(2+) elevations driven by release of intracellular Ca(2+) stores that culminate in motile activity in turn modifying bone resorptive activity. However, such triggering is controlled by ambient Ca(2+) rather than membrane potential with features strongly suggestive of control by a surface membrane Ca(2+) 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 Ca(2+) possibly through its otherwise intraluminal positioned low-affinity Ca(2+)-binding site in parallel with the SOICR mechanism in cardiac muscle. Such a mechanism could interact with other osteoclast processes transferring Ca(2+) between cytosol, intracellular stores and extracellular space and be integrated with systemic processes regulating Ca(2+) homeostasis.
Huang
Christopher L-H
CL
Physiological Laboratory, University of Cambridge, Cambridge, UK. clh11@cam.ac.uk
Sun
Li
L
Fraser
James A
JA
Grace
Andrew A
AA
Zaidi
Mone
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D054792:Muscle, Striated / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium