Evidence that a ryanodine receptor triggers signal transduction in the osteoclast.
We have investigated the effect of the alkaloid ryanodine on the release of intracellularly stored Ca2+ in response to activation of the osteoclast Ca2+ receptor by the surrogate agonist, Ni2+, Ni2+ (6 mM) in the presence of ethylene-glycol bis-(aminoethyl ether) tetraacetic acid (EGTA) (1.2 mM) and valinomycin (5 microM) induced a transient elevation of cytosolic [Ca2+] in fura 2-loaded osteoclasts. This transient was superimposed upon a small steady elevation of cytosolic [Ca2+] induced by the initial application of valinomycin alone. Ryanodine (10 microM) completely abolished such responsiveness. However, cytosolic [Ca2+] transients were restored when osteoclasts were depolarized by the extracellular inclusion of 100 mM-[K+] in the same solution. Thus, we demonstrate a sensitivity of the osteoclast signal transduction system to ryanodine for the first time to our knowledge.
Zaidi
M
M
Bone and Mineral Metabolism Unit, St. George's Hospital Medical School, London, U.K.
Shankar
V S
VS
Towhidul Alam
A S
AS
Moonga
B S
BS
Pazianas
M
M
Huang
C L
CL
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D010010:Osteoclasts / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel; D015398:Signal Transduction / Q000187:drug effects; D014634:Valinomycin / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D011950:Receptors, Cholinergic; D019837:Ryanodine Receptor Calcium Release Channel; D014634:Valinomycin; D009532:Nickel; D002118:Calcium