Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney.

Carbonic anhydrases (CAs), because they catalyze the interconversion of carbon dioxide (CO 2 ) and water into bicarbonate (HCO 3 - ) 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 HCO 3 - in specific nephron segments. Among these transporters are the Na + -coupled HCO 3 - transporters (NCBTs) and the Cl - -HCO 3 - exchangers (AEs)-members of the "solute-linked carrier" 4 (SLC4) family. All of these transporters have traditionally been regarded as "HCO 3 - " transporters. However, recently our group has demonstrated that two of the NCBTs carry CO 3 2- rather than HCO 3 - and has hypothesized that all NCBTs follow suit. In this review, we examine current knowledge on the role of CAs and "HCO 3 - " transporters of the SLC4 family in renal acid-base physiology and discuss how our recent findings impact renal acid secretion, including HCO 3 - reabsorption. Traditionally, investigators have associated CAs with producing or consuming solutes (CO 2 , HCO 3 - , and H + ) and thus ensuring their efficient transport across cell membranes. In the case of CO 3 2- 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.