Characterization of the Osteoclast Ruffled Border Chloride Channel and Its Role in Bone Resorption*
- From the Departments of ‡Cell Biology and Physiology,‖Pathology, and **Medicine, Washington University School of Medicine, St. Louis, Missouri 63110 and the ¶Department of Pathology, University of Alabama at Birmingham and Laboratory Service, Veterans Administration Medical Center, Birmingham, Alabama 35294
Abstract
Bone resorption by osteoclasts requires massive transcellular acid transport, which is accomplished by the parallel action of a V-type proton pump and a chloride channel in the osteoclast ruffled border. We have studied the molecular basis for the appearance of acid transport as avian bone marrow mononuclear cells acquire a bone resorptive phenotype in vitro. We demonstrate a critical role for regulated expression of a ruffled border chloride channel as the cells become competent to resorb bone. Molecular characterization of the chloride channel shows that it is related to the renal microsomal chloride channel, p64. In planar bilayers, the ruffled border channel is a stilbene sulfonate-inhibitable, outwardly rectifying chloride channel. A mechanism by which outward rectification of the single channel chloride current could allow efficient regulation of acidification by the channel is discussed.
Footnotes
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↵* This work was supported in part by National Institutes of Health Grant AR42370, by the Monsanto-Searle/Washington University Biomedical Program (to P. H. S. and J. C. E.), and by Grant R29DK46212 (to J. C. E.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵§ To whom correspondence should be addressed: Dept. of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110. Tel.: 314-362-2223; Fax: 314-362-7463; E-mail: paul{at}cellbio.wustl.edu.
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↵1 The abbreviations used are: PBS, phosphate-buffered saline; PAGE, polyacrylamide gel electrophoresis; DNDS, 4,4′-dinitrostilbene-2,2′-disulfonic acid; DIDS, 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid; kb, kilobase(s).
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- Received January 21, 1997.
- Revision received April 29, 1997.
