Intercalated cell H+/OH- transporter expression is reduced in Slc26a4 null mice

Slc26a4 ( Pds) encodes pendrin, a Cl-/HCO3- 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 P-CO2 were much lower in Slc26a4 null relative to wild-type mice due to reduced urinary buffering of secreted H+ by HCO3- . 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.