Carbonic anhydrase-dependent bicarbonate transport in the kidney

Carbonic anhydrase is abundantly distributed in renal tissue and functions, as in other epithelia, to catalyze the hydration-dehydration reaction of CO2. The proximal tubule is responsible for at least 80% of whole kidney bicarbonate transport and is mediated by proton secretion. Membrane-bound carbonic anhydrase appears to function primarily to prevent the rapid development of limiting pH gradients in this segment, and contributes importantly to the ability of this "leaky" epithelium to transport bicarbonate at high rates. Bicarbonate transport beyond the proximal tubule occurs in the loop of Henle and the medullary collecting tubule. After complete inhibition of the enzyme, bicarbonate appears to be transported passively as a result of favorable outwardly directed bicarbonate concentration gradients that are generated in the tubule lumen of more distal segments by water abstraction. This finding explains the widely appreciated, but seemingly paradoxical, view that complete inhibition of the renal enzyme results in excretion of only 30% of the filtered bicarbonate load. Although an additional role of carbonic anhydrase in mediating NaCl transport in the cortical thick ascending limb of Henle has been proposed, further investigation regarding the significance of this process is in order.