Collecting Duct Intercalated Cell Function and Regulation

Abstract

Intercalated cells are kidney tubule epithelial cells with important roles in the regulation of acid-base homeostasis. However, in recent years the understanding of the function of the intercalated cell has become greatly enhanced and has shaped a new model for how the distal segments of the kidney tubule integrate salt and water reabsorption, potassium homeostasis, and acid-base status. These cells appear in the late distal convoluted tubule or in the connecting segment, depending on the species. They are most abundant in the collecting duct, where they can be detected all the way from the cortex to the initial part of the inner medulla. Intercalated cells are interspersed among the more numerous segment-specific principal cells. There are three types of intercalated cells, each having distinct structures and expressing different ensembles of transport proteins that translate into very different functions in the processing of the urine. This review includes recent findings on how intercalated cells regulate their intracellular milieu and contribute to acid-base regulation and sodium, chloride, and potassium homeostasis, thus highlighting their potential role as targets for the treatment of hypertension. Their novel regulation by paracrine signals in the collecting duct is also discussed. Finally, this article addresses their role as part of the innate immune system of the kidney tubule.

Acid-Base Homeostasis

“…A significant portion of this increased H 1 secretion is through insertion of additional H 1 -ATPase by fusion of subapical vesicles (containing H 1 -ATPase) with the plasma membrane. These processes are mediated, in part, by a variety of signal transduction systems (cAMP, cGMP, and PLC/protein kinase C) (39,41). A role for soluble adenyl cyclase, G protein-coupled receptor 4, and other mechanisms in sensing pH changes or acid-base loads has also been proposed in type A ICs and previously discussed in this series (39,41).…”

“…There are at least three types of ICs: type A or a ICs, which secrete H 1 ; type B or b ICs, which secrete HCO 3 2 ; and non-A, non-B ICs, with a range of function that remains under investigation. These have been recently reviewed in this series (39) (Figure 4).…”

“…In the cortical collecting duct, in addition to HCO 3 2 reabsorption by type A ICs, simultaneous HCO 3 2 secretion occurs in separate cells, the type B ICs (39,50). This process involves an apical chloride-bicarbonate exchanger and a basolateral H 1 -ATPase (51).…”

“…In animal studies, HCO 3 2 secretion is stimulated by alkali loading and inhibited by low luminal chloride. The basolateral H 1 -ATPase is the same pump as in the apical membrane of type A IC, but the apical Cl 2 / HCO 3 2 exchanger has been identified as pendrin, a protein first identified as being abnormal in some patients with hereditary deafness (39,52,53). The importance of HCO 3 2 secretion in human pathophysiologic circumstances is not well characterized but may be important in the maintenance and/or repair of metabolic alkalosis.…”

“…These processes are mediated, in part, by a variety of signal transduction systems (cAMP, cGMP, and PLC/protein kinase C) (39,41). A role for soluble adenyl cyclase, G protein-coupled receptor 4, and other mechanisms in sensing pH changes or acid-base loads has also been proposed in type A ICs and previously discussed in this series (39,41). Although the response to acidosis begins with these fairly rapid changes, chronic acidosis leads to a variety of changes in mRNA and protein levels of various transporters.…”