Physiology and molecular biology of renal carbonic anhydrase

Carbonic anhydrase (CA) is an important enzyme in the kidney and facilitates renal acidification by catalvzing the reversible hydration of CO2 and the dehydration of bicarbonate. Currently, 14 isoforms of CA have been identified, of which CA II, CA IV, CA XII and possibly CA XIV are expressed by the kidney. Cytosolic CA II comprises -95% of renal CA, with the remainder being membrane-associated. CA II, while being nearly ubiquitous in the body, is also expressed by a large number of nephron segments, including proximal convoluted and straight tubules, thin descending limbs of Henle's loop, thick ascending limbs of Henle's loop in some species, intercalated cells of the cortical and medullary collecting ducts, and weakly in principal cells and inner medullary collecting ducts of some species; CA II is not found in glomeruli. Most membrane-associated CA is attributed to isoform IV, which is linked to the apical membrane via a glycosylphosphatidylinositol anchor; however, there is data showing that CA IV is also localized on the basolateral membranes of proximal tubule cells. How the basolateral form is linked to the membrane is not yet understood. CA IV is expressed on the luminal membrane of proximal convoluted and straight tubules, alpha-intercalated cells of cortical and medullary collecting ducts, and all cells of initial inner medullary collecting ducts. Another membrane isoform, CA XII, is also present in the kidney and probably situated in the basolateral membrane as a single-pass transmembrane protein. One study localizes CA XII to the distal nephron, while another places it in proximal tubules and inner medullary collecting ducts; confirmatory studies are needed for CA XII. The localization of CA XIV in the kidney is still under investigation. Functional studies clearly show the importance of apical and basolateral membrane CAs in mediating bicarbonate and fluid absorption in proximal tubules and of the apical membrane CA activity in mediating H+ secretion in the collecting duct. To establish other roles for CA in the kidney will require further kinetic, functional, immunolocalization and cloning studies.