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. This transport is a major metabolic activity of osteoclasts requiring an electrogenic H(+)-ATPase, a conductive chloride channel, a chloride-bicarbonate exchanger, carbonic anhydrase, and functional/morphological polarization of the cell. The osteoclast H(+)-ATPase is electrically coupled to a chloride channel in the ruffled membrane as are similar transport activities found in acidic intracellular vesicles, but the vanadate sensitivity of the osteoclast proton pump is intermediated between that of the E- and v-type proton pumps. The carbonic anhydrase and chloride-bicarbonate exchange provide an interface with pH regulation and integrate bone resorption into systemic acid-base balance. With the molecular mediators of bone resorption being known we may consider the control of bone resorption with an eye to mechanism and specificity that has not previously been possible. The effects of systemic acidosis to increase bone resorption and the effects of carbonic anhydrase deficiency are consistent with our mechanism of osteoclast ion transport.
Schlesinger
P H
PH
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Mo. 63110.
Mattsson
J P
JP
Blair
H C
HC
D000143:Acids / Q000493:pharmacokinetics*; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology*; D008566:Membranes / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D017494:Proton Pumps / Q000502:physiology
D000143:Acids; D017494:Proton Pumps