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

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