抄録
Osteoclasts resolve calcified tissue by secreting a massive amount of protons and play significant roles in bone remodeling and bodily Ca2+ metabolism. Osteoclasts express two distinct types of acid-secreting pathways, the vacuolar type H+-ATPase (V-ATPase) and the voltage-gated proton channel (H+ channel). Both could acidify the extracellular space, but would work differently in cellular functions. The V-ATPase is rich at the plasma membrane faced to bone surface (the ruffled membrane) and serves as the primary mechanism responsible for H+ secretion into the resorption pit. Inadequate control of the H+ pump may impair bone remodeling and cause pathological states like osteoporosis. We for the first time recorded the proton currents mediated by plasmalemmal V-ATPases in murine osteoclast-like cells. The H+ pump current was tiny as compared to that of the H+ channel, but continued to carry protons uphill against large negative electrochemical gradients. The V-ATPase activity was also regulated by the concentration of intracellular ATP, interaction with the actin cytoskeleton, recruitment from the internal vesicles, the membrane potential and pH gradients across the membrane. In addition, we found an elevation of extracellular calcium reduced the V-ATPase activity. Accumulation of acids and calcium in the resorption pit might serve as a negative feedback mechanism for the V-ATPase in osteoclasts. H+ releasing ability of the plasmalemmal V-ATPase could change over a wide range in response to variable cellular conditions. [J Physiol Sci. 2007;57 Suppl:S49]
