CHARACTERIZATION OF THE OSTEOCLAST RUFFLED BORDER CHLORIDE CHANNEL AND ITS ROLE IN BONE-RESORPTION

Bone resorption by osteoclasts requires massive transcellular acid tra nsport, which is accomplished by the parallel action of a V-type proto n pump and a chloride channel in the osteoclast ruffled border. We hav e studied the molecular basis for the appearance of acid transport as avian bone marrow mononuclear cells acquire a bone resorptive phenotyp e in vitro. We demonstrate a critical role for regulated expression of a ruffled border chloride channel as the cells become competent to re sorb bone. Molecular characterization of the chloride channel shows th at it is related to the renal microsomal chloride channel, p64. In pla nar bilayers, the ruffled border channel is a stilbene sulfonate-inhib itable, outwardly rectifying chloride channel. A mechanism by which ou tward rectification of the single channel chloride current could allow efficient regulation of acidification by the channel is discussed.