Linkage of extracellular and intracellular control of cytosolic Ca2+ in rat osteoclasts in the presence of thapsigargin

Mone Zaidi, Vijai S. Shankar, Christopher M.R. Bax, Bridget E. Bax, Peter J.R. Bevis, Michael Pazianas, A. S.M.Towhidul Alam, Baljit S. Moonga, Christopher L.‐H Huang

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Abstract

Cytosolic [Ca2+] was measured in single osteoclasts using fura‐2 in experiments investigating the effects of Ca2+ “receptor” activation using thapsigargin as a means of depleting intracellular Ca2+ stores. Application of 4 μM thapsigargin to osteoclasts in Ca2+‐free solutions resulted in an elevation of cytosolic [Ca2+]. Under similar conditions, activation of the osteoclast Ca2+ receptor by the substitute divalent cation agonist, Ni2+, resulted in a transient elevation of cytosolic [Ca2+]. In both instances, restoration of extracellular [Ca2+] to 1.25 mM resulted in an “overshoot” of cytosolic [Ca2+]. Prior depletion of intracellular Ca2+ stores by thapsigargin markedly reduced the magnitude of the cytosolic [Ca2+] response to a subsequent application of 5 mM Ni2+. The application of 2 μM thapsigargin to intercept the falling phase of the Ni2+‐induced cytosolic Ca2+ signal resulted in a sustained elevation of cytosolic [Ca2+], which was terminated by a second application of the same Ni2+. Furthermore, the sustained elevation of cytosolic [Ca2+] induced by thapsigargin application alone was abolished by late application of Ni2+. We conclude that activation of the surface membrane Ca2+ receptor on the osteoclast results in the cytosolic release of Ca2+ from intracellular storage organelles; the refilling of such stores depends upon a thapsigargin‐sensitive Ca2+‐ATPase; store depletion induces capacitative Ca2+ influx; and the Ca2+ influx pathway is sensitive to blockade by Ni2+.

Original languageEnglish
Pages (from-to)961-967
Number of pages7
JournalJournal of Bone and Mineral Research
Volume8
Issue number8
DOIs
StatePublished - Aug 1993
Externally publishedYes

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