Regulation of acidification in the rat inner medullary collecting duct

The inner medullary collecting duct (IMCD) is the most distal portion of the nephron and plays an important role in urinary net acid excretion. The terminal or distal two thirds of the IMCD is lined by a single cell type, now termed the IMCD cell, which not only secretes protons, but transports sodium and potassium and responds to many hormones. The IMCD may account for greater than 50% of the excreted acid under control conditions and, during acidosis, absolute acid secretion may increase fivefold. Conversely, during alkalemia, acid secretion by this segment is abolished. Thus, the IMCD responds appropriately to perturbations in systemic acid-base balance. Furthermore, models of renal tubular acidosis have been demonstrated along this nephron segment. Three transporters that are important in acid-base control, the Na+/H+ and the Cl-/HCO3- exchanger and an active proton pump, presumably an H(+)-adenosine phosphatase (ATPase), have been demonstrated in IMCD cells. The former two are situated in the basolateral membrane, while the latter is situated in the apical membrane. Only the proton pump is responsible for actual acid addition to the urine. The intracellular mechanisms that modulate the proton pump are just beginning to be defined. It is likely that acid secretory activity involves exocytic insertion of additional pumps, and is dependent on cell pH changes, which are the primary signal, and on changes in intracellular calcium concentration and calmodulin activity, which are the second messengers.