title: Intercalated cell H+/OH- transporter expression is reduced in Slc26a4 null mice.
abstract: Slc26a4 (Pds) encodes pendrin, a Cl(-)/HCO(3)(-) exchanger expressed in the apical region of type B and non-A, non-B cells, which mediates secretion of OH(-) equivalents. Thus genetic disruption of Slc26a4 leads to systemic alkalosis in some treatment models. However, humans and mice with genetic disruption of Slc26a4 have normal acid-base balance under basal conditions. Thus we asked: 1) Is net acid excretion altered in Slc26a4 (-/-) mice under basal conditions? 2) In the absence of pendrin-mediated OH(-) secretion, are increases in intracellular and systemic pH minimized through changes in intercalated cell subtype abundance or intercalated cell H(+)/OH(-) transporter expression? To answer these questions, net acid excretion and H(+)/OH(-) transporter expression were examined in Slc26a4 (-/-) and Slc26a4 (+/+) mice using balance studies, immunolocalization, and immunoblotting. Excretion of ammonium, titratable acid, and citrate were the same in Slc26a4 null and wild-type mice. However, urinary pH and Pco(2) were much lower in Slc26a4 null relative to wild-type mice due to reduced urinary buffering of secreted H(+) by HCO(3)(-). Abundance of non-A, but not type A intercalated cells, was reduced within the cortical collecting ducts of Slc26a4 null mice. Moreover, kidneys from Slc26a4 null mice had reduced H(+)-ATPase, NBC3 and RhBG total protein expression, particularly within type B and non-A, non-B intercalated cells, although RhCG protein expression was unchanged. Reduced intercalated cell H(+)/OH(-) transporter expression is observed in Slc26a4 null mice, which likely attenuates the rise in intracellular and systemic pH expected with genetic disruption of Slc26a4.
authors.affiliation: Department of Medicine, Emory University, Atlanta, Georgia, USA.
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Jill W
authors.initials: JW
authors.lastname: Verlander
authors.forename: Sharon W
authors.initials: SW
authors.lastname: Matthews
authors.forename: Ira
authors.initials: I
authors.lastname: Kurtz
authors.forename: Wonkyong
authors.initials: W
authors.lastname: Shin
authors.forename: I David
authors.initials: ID
authors.lastname: Weiner
authors.forename: Lorraine A
authors.initials: LA
authors.lastname: Everett
authors.forename: Eric D
authors.initials: ED
authors.lastname: Green
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Susan M
authors.initials: SM
authors.lastname: Wall
mesh_terms: D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D027321:Anion Transport Proteins / Q000172:deficiency* / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D006180:Proton-Translocating ATPases / Q000096:biosynthesis* / Q000378:metabolism; D027982:Sodium-Bicarbonate Symporters / Q000096:biosynthesis*; D000076988:Sulfate Transporters
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D027321:Anion Transport Proteins; C494849:Slc26a4 protein, mouse; C498904:Slc4a7 protein, mouse; D027982:Sodium-Bicarbonate Symporters; D000076988:Sulfate Transporters; D006180:Proton-Translocating ATPases