Carbonic anhydrases (CAs), because they catalyze the interconversion of carbon dioxide (CO2) and water into bicarbonate (HCO3-) and protons (H+), thereby influencing pH, are near the core of virtually all physiological processes in the body. In the kidneys, soluble and membrane-associated CAs and their synergy with acid-base transporters play important roles in urinary acid secretion, the largest component of which is the reabsorption of HCO3- in specific nephron segments. Among these transporters are the Na+-coupled HCO3- transporters (NCBTs) and the Cl--HCO3- exchangers (AEs)-members of the "solute-linked carrier" 4 (SLC4) family. All of these transporters have traditionally been regarded as "HCO3-" transporters. However, recently our group has demonstrated that two of the NCBTs carry CO32- rather than HCO3- and has hypothesized that all NCBTs follow suit. In this review, we examine current knowledge on the role of CAs and "HCO3-" transporters of the SLC4 family in renal acid-base physiology and discuss how our recent findings impact renal acid secretion, including HCO3- reabsorption. Traditionally, investigators have associated CAs with producing or consuming solutes (CO2, HCO3-, and H+) and thus ensuring their efficient transport across cell membranes. In the case of CO32- transport by NCBTs, however, we hypothesize that the role of membrane-associated CAs is not the appreciable production or consumption of substrates but the minimization of pH changes in nanodomains near the membrane.
Keywords: acid–base homeostasis; bicarbonate; carbonate; cell membranes; renal tubules; transporters.