OSTEOCLASTIC ACID TRANSPORT - MECHANISM AND IMPLICATIONS FOR PHYSIOLOGICAL AND PHARMACOLOGICAL REGULATION

In order to solubilize bone mineral and degrade the organic matrix of bone osteoclasts must secrete 1-2 protons for every Ca2+ liberated. Th is transport is a major metabolic activity of osteoclasts requiring an electrogenic H+-ATPase, a conductive chloride channel, a chloride-bic arbonate exchanger, carbonic anhydrase, and functional/morphological p olarization of the cell. The osteoclast H+-ATPase is electrically coup led to a chloride channel in the ruffled membrane as are similar trans port activities found in acidic intracellular vesicles, but the vanada te sensitivity of the osteoclast proton pump is intermediated between that of the E- and v-type proton pumps. The carbonic anhydrase and chl oride-bicarbonate exchange provide an interface with pH regulation and integrate bone resorption into systemic acid-base balance. With the m olecular mediators of bone resorption being known we may consider the control of bone resorption with an eye to mechanism and specificity th at has not previously been possible. The effects of systemic acidosis to increase bone resorption and the effects of carbonic anhydrase defi ciency are consistent with our mechanism of osteoclast ion transport.