HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nordström, T. Articles by Grinstein, S. Search for Related Content PubMed PubMed Citation Articles by Nordström, T. Articles by Grinstein, S. Social Bookmarking                      What's this?

Volume 272, Number 10, Issue of March 7, 1997 pp. 6354-6360
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Chronic Extracellular Acidosis Induces Plasmalemmal Vacuolar Type H⁺ ATPase Activity in Osteoclasts

(Received for publication, October 30, 1996, and in revised form, December 22, 1996)

Tommy Nordström ^§ , Lamara D. Shrode , Ori D. Rotstein ^§ , Robert Romanek , Tetsuya Goto , Johannes N. M. Heersche , Morris F. Manolson , Guy F. Brisseau ^§ and Sergio Grinstein

From the  Division of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8, the ^§ Department of Surgery, Toronto Hospital, Toronto, Ontario, Canada M5G 2C4, and the  Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada M5G 1G6

Proton extrusion into an extracellular resorption compartment is an essential component of bone degradation by osteoclasts. Chronic metabolic acidosis is known to induce negative calcium balance and bone loss by stimulating osteoclastic bone resorption, but the underlying mechanism is not known. The present studies were undertaken to evaluate whether chronic acidosis affects proton extrusion mechanisms in osteoclasts cultured on glass coverslips. Acidosis, mimicked experimentally by maintaining the cells at extracellular pH 6.5, rapidly lowered intracellular pH to 6.8. However, after 2 hours, a proportion of cells demonstrated the capacity to restore intracellular pH to near normal levels. To define the mechanism responsible for this recovery, the activity of individual H⁺ transport pathways was analyzed. We found that chronic acid treatment for up to 6 h did not significantly affect the cellular buffering power or Na⁺/H⁺ antiport activity. In contrast, chronic acidosis activated vacuolar H⁺ pumps in the osteoclasts. Although only ~5% of the control cells displayed proton pump activity, about 40% of cells kept at extracellular pH 6.5 for 4-6 h were able to recover from the acute acid load by means of bafilomycin A₁-sensitive proton extrusion. Conversely, the H⁺-selective conductance recently described in the plasma membrane of osteoclasts was clearly inhibited in the cells exposed to chronic acidosis. Following acid treatment, the activation threshold of the H⁺ conductance was shifted to more positive potentials, and the current density was significantly reduced. Considered together, these results suggest that induction of plasmalemmal vacuolar type ATPase activity by chronic acidosis, generated either systemically due to metabolic disease or locally at sites of inflammation, is likely to stimulate osteoclastic bone resorption and thus to promote bone loss.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. E. DeCoursey Voltage-gated proton channels: what's next? J. Physiol., November 15, 2008; 586(22): 5305 - 5324. [Abstract] [Full Text] [PDF]

				T. R. Arnett Extracellular pH Regulates Bone Cell Function J. Nutr., February 1, 2008; 138(2): 415S - 418S. [Abstract] [Full Text] [PDF]

				S. V. Komarova, A. Pereverzev, J. W. Shum, S. M. Sims, and S. J. Dixon Convergent signaling by acidosis and receptor activator of NF-{kappa}B ligand (RANKL) on the calcium/calcineurin/NFAT pathway in osteoclasts PNAS, February 15, 2005; 102(7): 2643 - 2648. [Abstract] [Full Text] [PDF]

				T. E. Decoursey Voltage-Gated Proton Channels and Other Proton Transfer Pathways Physiol Rev, April 1, 2003; 83(2): 475 - 579. [Abstract] [Full Text] [PDF]

				M. Maurer, W. Riesen, J. Muser, H. N. Hulter, and R. Krapf Neutralization of Western diet inhibits bone resorption independently of K intake and reduces cortisol secretion in humans Am J Physiol Renal Physiol, January 1, 2003; 284(1): F32 - F40. [Abstract] [Full Text] [PDF]

				R. L. Lees and J. N. M. Heersche Differences in regulation of pHi in large (>= 10 nuclei) and small (<= 5 nuclei) osteoclasts Am J Physiol Cell Physiol, September 1, 2000; 279(3): C751 - C761. [Abstract] [Full Text] [PDF]

				N. Altan, Y. Chen, M. Schindler, and S. M. Simon Tamoxifen inhibits acidification in cells independent of the estrogen receptor PNAS, April 13, 1999; 96(8): 4432 - 4437. [Abstract] [Full Text] [PDF]

				H. Sakai, F. Nakamura, and M. Kuno Synergetic activation of outwardly rectifying Cl- currents by hypotonic stress and external Ca2+ in murine osteoclasts J. Physiol., February 15, 1999; 515(1): 157 - 168. [Abstract] [Full Text] [PDF]

				E. Roussa, F. Thevenod, I. Sabolic, C. M. Herak-Kramberger, W. Nastainczyk, R. Bock, and I. Schulz Immunolocalization of Vacuolar-type H+-ATPase in Rat Submandibular Gland and Adaptive Changes Induced by Acid-Base Disturbances J. Histochem. Cytochem., January 1, 1998; 46(1): 91 - 100. [Abstract] [Full Text]