Cytosolic pH regulation in osteoblasts
Abstract
The process of bone formation depends on an optimal alkaline pH in the extracellular milieu surrounding the osteoblast. To the extent that ionic composition of an extracellular environment is determined by events taking place inside the cell, it is conceivable that the pH in the fluid outside the osteoblast is affected by cytosolic pH (pHi) regulation by these cells. Under HEPES-buffered conditions, the main pH regulatory mechanism is the ubiquitous acid-extruding mechanism, Na+/H+ exchange. However, under the more physiologic HCO3- environment, one can identify three additional acid-bone transporters: Na(+)-independent Cl-/HCO3- exchanger, Na+(HCO3-)3 cotransporter, and HCO(3-)-conductive pathway. In addition to their role in regulation of pHi in the osteoblast, these transporters also play a role in volume regulation of these cells both under hypertonic conditions (regulatory volume increase) and during osmotic swelling (regulatory volume decrease). Second messengers produced by calciotropic hormones (e.g. cytosolic Ca2+, cAMP) regulate the activity of Na+/H+ exchanger and Cl-/HCO3- exchanger.
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