Mechanisms of active H+ secretion in the proximal tubule

This Editorial Review describes the mechanisms that have been identified for mediating active H+ secretion across the luminal membrane of the proximal tubular cell. These include Na+-H+ exchange, Na+-phosphate cotransport, organic anion-OH- exchange, ATP-driven H+ transport, and redox-driven H+ transport. Of these, Na+-H+ exchange appears to be the most important. Indeed, there is no conclusive evidence against the concept that luminal membrane Na+-H+ exchange is the principal if not the sole mechanism for mediating active H+ secretion in the proximal tubule. The transport properties of the Na+-H+ exchanger, particularly its striking sensitivity to intracellular pH, can explain many aspects of how the rate of active H+ secretion in the proximal tubule is regulated in response to various physiologic stimuli. Certainly, important physiologic roles for other H+ secretory mechanisms, especially those involving primary active H+ secretion, have not been excluded. Nevertheless, there is not yet definitive proof that ATP-driven or redox-driven H+ pumps are located on the luminal membrane itself or that they significantly contribute to transtubular H+ secretion.