Characterization of the osteoclast ruffled border chloride channel and its role in bone resorption

Paul H. Schlesinger, Harry C. Blair, Steven L. Teitelbaum, John C. Edwards

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

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.

Original languageEnglish
Pages (from-to)18636-18643
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number30
DOIs
StatePublished - 1997

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