Identification and characterization of a sodium/calcium exchanger, NCX-1, in osteoclasts and its role in bone resorption

Baljit S. Moonga, Robert Davidson, Li Sun, Olugbenga A. Adebanjo, James Moser, Mohammad Abedin, Neeha Zaidi, Christopher L.H. Huang, Mone Zaidi

Research output: Contribution to journalArticle

Abstract

We provide the first demonstration for a Na+/Ca2+ exchanger, NCX-1, in the osteoclast. We speculate that by using Na+ exchange, NCX-1 couples H+ extrusion with Ca2+ fluxes during bone resorption. Microspectrofluorimetry of fura-2-loaded osteoclasts revealed a rapid and sustained, but reversible, cytosolic Ca2+ elevation upon Na+ withdrawal. This elevation was abolished by the cytosolic introduction (by gentle permeabilization) of a highly specific Na+/Ca2+ exchange inhibitor peptide, XIP, but not its inactive analogue, sXIP. Confocal microscopy revealed intense plasma membrane immunofluorescence with an isoform-specific monoclonal anti-NCX-1 antibody applied to gently permeabilized osteoclasts. Electrophysiological studies using excised outside-in membrane patches showed a low-conductance, Na+-selective, dichlorobenzamil-sensitive, amiloride-insensitive channel that we tentatively assigned as being an NCX. Finally, to examine for physiological relevance, an osteoclast resorption (pit) assay was performed. There was a dramatic reduction of bone resorption following NCX-1 inhibition by dichloroben- zamil and XIP (but not with S-XIP). Together, the results suggest that a functional NCX, likely NCX-1, is involved in the regulation of osteoclast cytosolic Ca2+ and bone resorption.

Original languageEnglish (US)
Pages (from-to)770-775
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume283
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Bone resorption
  • Na/Ca exchange
  • Osteoclasts
  • Osteoporosis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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