A new member of the HCO3- transporter superfamily is an apical anion exchanger of beta-intercalated cells in the kidney

The kidneys play pivotal roles in acid-base homeostasis, and the acid-secre ting (alpha -type) and bicarbonate-secreting (beta -type) intercalated cell s in the collecting ducts are major sites for the final modulation of urina ry acid secretion. Since the H+-ATPase and anion exchanger activities in th ese two types of intercalated cells exhibit opposite polarities, it has bee n suggested that the alpha- and beta -intercalated cells are interchangeabl e via a cell polarity change. Immunohistological studies, however, have fai led to confirm that the apical anion exchanger of beta -intercalated cells is the band 3 protein localized to the basolateral membrane of alpha -inher calated cells. In the present study, we show the evidence that a novel memb er of the anion exchanger and sodium bicarbonate cotransporter superfamily is an apical anion exchanger of beta -intercalated cells. Cloned cDNA from the beta -intercalated cells shows about 30% homology with anion exchanger types 1-3, and functional expression of this protein in COS-7 cells and Xen opus oocytes showed sodium-independent and 4,4' -diisothiocyanostilbene-2,2 '-disulfonic acid-insensitive anion exchanger activity. Furthermore, immuno histological studies revealed that this novel anion exchanger is present on the apical membrane of beta -intercalated cells, although some beta -inter calated cells were negative for AE4 staining. We conclude that our newly cl oned transporter is an apical anion exchanger of the beta -intercalated cel ls, whereas our data do not exclude the possibility that there may be anoth er form of anion exchanger in these cells.