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One of the major tasks of the renal proximal tubule is to secrete acid into the tubule lumen, thereby reabsorbing approximately 80% of the filtered HCO3- as well as generating new HCO3- for regulating blood pH. This review summarizes the cellular and molecular events that underlie four major processes in HCO3- reabsorption. The first is CO2 entry across the apical membrane, which in large part occurs via a gas channel (aquaporin 1) and acidifies the cell. The second process is apical H+ secretion via Na-H exchange and H+ pumping, processes that can be studied using the NH4+ prepulse technique. The third process is the basolateral exit of HCO3- via the electrogenic Na/HCO3 co-transporter, which is the subject of at least 10 mutations that cause severe proximal renal tubule acidosis in humans. The final process is the regulation of overall HCO3- reabsorption by CO2 and HCO3- sensors at the basolateral membrane. Together, these processes ensure that the proximal tubule responds appropriately to acute acid-base disturbances and thereby contributes to the regulation of blood pH.

Acid-Base Transport by the Renal Proximal Tubule