SLC26A7: a basolateral Cl^-/HCO₃^-exchanger specific to intercalated cells of the outer medullary collecting duct

Abstract

The outer medullary collecting duct (OMCD) plays an important role in bicarbonate reabsorption and acid-base regulation. An apical V-type H+-ATPase and a basolateral [Formula: see text] exchanger, located in intercalated cells of OMCD, mediate the bicarbonate reabsorption. Here we report the identification of a new basolateral [Formula: see text] exchanger in OMCD intercalated cells in rat kidney. Northern hybridizations demonstrated the predominant expression of this transporter, also known as SLC26A7, in the outer medulla, with lower expression levels in the inner medulla. SLC26A7 was recognized as a ∼90-kDa band in the outer medulla by immunoblot analysis and was localized on the basolateral membrane of a subset of OMCD cells by immunocytochemical staining. No labeling was detected in the cortex. Double-immunofluorescence labeling with the aquaporin-2 and SLC26A7 antibodies or anion exchanger-1 and SLC26A7 antibodies identified the SLC26A7-expressing cells as α-intercalated cells. Functional studies in oocytes demonstrated that increasing the osmolality of the media (to simulate the physiological milieu in the medulla) increased the [Formula: see text] exchanger activity mediated via SLC26A7 by about threefold ( P < 0.02 vs. normal condition). We propose that SLC26A7 is a basolateral [Formula: see text] exchanger in intercalated cells of the OMCD and may play an important role in bicarbonate reabsorption in medullary collecting duct.

Chloride/Bicarbonate Exchanger SLC26A7 Is Localized in Endosomes in Medullary Collecting Duct Cells and Is Targeted to the Basolateral Membrane in Hypertonicity and Potassium Depletion

“…BB666404) and an antibody raised against human SLC26A7 were used for immunofluorescence labeling (8,19).…”

“…Functional and molecular studies from our laboratory demonstrated that SLC26A7 is a chloride/bicarbonate exchanger (7). In the stomach, SLC26A7 is expressed on the basolateral membrane of the acid-secreting gastric parietal cells (7), whereas in the kidney, it localizes on the basolateral membrane of acid-secreting A-intercalated (A-IC) cells of the outer medullary collecting duct (OMCD) (8,19). OMCD has the highest rate of acid secretion among the collecting duct segments (20).…”

“…Proton (acid) secretion across the apical membrane of A-IC cells in OMCD via vacuolar H ϩ -ATPase (and to some extent via H ϩ /K ϩ ATPase) results in the generation of intracellular bicar-bonate, which will be transported across the basolateral membrane into the peritubular space via basolateral Cl Ϫ /HCO 3 Ϫ exchanger (20,21). SLC26A7 co-localizes with AE1 (SLC4A1) on the basolateral membrane of A-IC cells of OMCD, indicating possible distinct roles for these two Cl Ϫ /HCO 3 Ϫ exchangers in acid secretion and bicarbonate absorption (8,19). A recent study indicated that SLC26A7 can function as a Cl Ϫ channel that is regulated by intracellular pH in the heterologous expression system (22).…”

Role of tubular secretion and carbonic anhydrase in vertebrate renal sulfate excretion

“…In addition to Cl Ϫ and formate, SLC26A6 has affinities for oxalate, HCO 3 Ϫ , and SO 4 2Ϫ (39,93). SLC26A7 has been localized to the BLM of rat outer medullary collecting duct cells where it has been hypothesized to function in HCO 3 Ϫ reabsorption (63). When expressed in Xenopus oocytes, SLC26A7 exhibits HCO 3 Ϫ , Cl Ϫ , oxalate, and SO 4 2Ϫ transport activity (47,63).…”

“…SLC26A7 has been localized to the BLM of rat outer medullary collecting duct cells where it has been hypothesized to function in HCO 3 Ϫ reabsorption (63). When expressed in Xenopus oocytes, SLC26A7 exhibits HCO 3 Ϫ , Cl Ϫ , oxalate, and SO 4 2Ϫ transport activity (47,63). SLC26A11 mRNA transcript is present in the mammalian kidney and displays DIDS-sensitive Na ϩ -independent SO 4 2Ϫ transport when expressed in insect Sf9 cells (92).…”