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Volume 272, Number 30, Issue of July 25, 1997 pp. 18636-18643
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Characterization of the Osteoclast Ruffled Border Chloride Channel and Its Role in Bone Resorption

(Received for publication, January 21, 1997, and in revised form, April 29, 1997)

Paul H. Schlesinger , Harry C. Blair ^¶ , Steven L. Teitelbaum and John C. Edwards ^**

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

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.

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