A New Member of the HCO₃^- Transporter Superfamily Is an Apical Anion Exchanger of β-Intercalated Cells in the Kidney

The kidneys play pivotal roles in acid-base homeostasis, and the acid-secreting (α-type) and bicarbonate-secreting (β-type) intercalated cells in the collecting ducts are major sites for the final modulation of urinary acid secretion. Since the H⁺-ATPase and anion exchanger activities in these two types of intercalated cells exhibit opposite polarities, it has been suggested that the α- and β-intercalated cells are interchangeable via a cell polarity change. Immunohistological studies, however, have failed to confirm that the apical anion exchanger of β-intercalated cells is the band 3 protein localized to the basolateral membrane of α-intercalated cells. In the present study, we show the evidence that a novel member of the anion exchanger and sodium bicarbonate cotransporter superfamily is an apical anion exchanger of β-intercalated cells. Cloned cDNA from the β-intercalated cells shows about 30% homology with anion exchanger types 1-3, and functional expression of this protein in COS-7 cells and Xenopus oocytes showed sodium-independent and 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid-insensitive anion exchanger activity. Furthermore, immunohistological studies revealed that this novel anion exchanger is present on the apical membrane of β-intercalated cells, although some β-intercalated cells were negative for AE4 staining. We conclude that our newly cloned transporter is an apical anion exchanger of the β-intercalated cells, whereas our data do not exclude the possibility that there may be another form of anion exchanger in these cells.