ROLE OF ION-EXCHANGERS IN MEDIATING NACL TRANSPORT IN THE PROXIMAL TUBULE

The reabsorption of NaCl in the proximal tubule occurs passively throu gh the paracellular pathway, and actively by a transcellular route. Tr anscellular NaCl transport involves Na+-coupled Cl- entry across the a pical membrane by two mechanisms involving Cl--organic anion exchange. One mechanism is Cl--formate exchange with recycling of formate from lumen to cell by H+-coupled formate transport in parallel with Na+-Hexchange. A second mechanism is Cl--oxalate exchange with recycling of oxalate from lumen to cell by oxalate-sulfate exchange in parallel wi th Na+-sulfate cotransport. Cl- exit across the basolateral membrane i s most likely mediated by Cl- channels. Apical membrane Na+-H+ exchang e is involved in mediating both NaHCO3 and NaCl reabsorption in the pr oximal tubule. Immunocytochemical studies indicate that NHE3 is the pr incipal Na+-H+ exchanger isoform expressed on the brush border membran e. Detection of NHE3 in a subapical, intracellular, vesicular compartm ent in proximal tubule cells is consistent with its possible regulatio n by membrane trafficking. That NHE3 is the isoform responsible for ap ical membrane Na+-H+ exchange activity is supported by studies of inhi bitor sensitivity, and by studies demonstrating increased expression o f NHE3 protein in association with enhanced Na+-H+ exchange activity d uring renal maturation and in response to glucocorticoids and metaboli c acidosis.