The renal AE4 transporter (Slc4a9) is essential for the upregulation of pendrin (Slc26a4) and prevents life threatening hypochloremic metabolic alkalosis during base loading
Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
Medientyp:
E-Artikel
Titel:
The renal AE4 transporter (Slc4a9) is essential for the upregulation of pendrin (Slc26a4) and prevents life threatening hypochloremic metabolic alkalosis during base loading
Beschreibung:
<jats:p>The renal transporter AE4 (Slc4a9) is localized to the basolateral membrane of type B intercalated cells (β‐ICs) in the collecting duct. Recently, it has been shown that β‐ICs not only contribute to renal HCO<jats:sub>3</jats:sub><jats:sup>−</jats:sup> secretion, but also to renal sodium (Na<jats:sup>+</jats:sup>) reabsorption during dietary salt restriction. Currently it is generally assumed that AE4 constitutes the primary basolateral Na<jats:sup>+</jats:sup> extrusion pathway in β‐ICs, but there is still no <jats:italic>in vivo</jats:italic> evidence of such a role. To test this hypothesis, we subjected AE4 knockout mice and their wild‐type littermates (WT) to either a salt (NaCl) deficient diet alone (10 days) or a salt deficient diet combined with an additional base load (230 mM NaHCO<jats:sub>3</jats:sub>, 7 days), and analyzed the effects of each diet on plasma volume, renal Na<jats:sup>+</jats:sup> and Cl<jats:sup>−</jats:sup> handling, renal protein expression levels of NHE3, NCC, ENaC and pendrin, plasma renin and aldosterone levels, and acid‐base homeostasis. Surprisingly, AE4 knockout mice did not show any signs of Na<jats:sup>+</jats:sup> loss or volume contraction or compensatory activation of other renal Na<jats:sup>+</jats:sup> reabsorption pathways under salt deficient diet. However, we observed that AE4 knockout mice developed a mild hypochloremic metabolic alkalosis under these conditions, which severely aggravated when the animals were additionally subjected to a base load (NaHCO<jats:sub>3</jats:sub>). In contrast, WT littermates maintained normal Na<jats:sup>+</jats:sup> and acid‐base balance under both diet regimes. While WT mice increased pendrin expression within the first day of base loading, this response was absent in AE knockout animals. These findings indicate that AE4 is dispensable for Na<jats:sup>+</jats:sup> homeostasis during salt restriction, but is essential for the stimulatory effect of alkalosis on the expression of the apical Cl<jats:sup>−</jats:sup>/HCO<jats:sub>3</jats:sub><jats:sup>−</jats:sup> exchanger pendrin. An insufficient function of AE4 facilitates the development of a life‐threatening hypochloremic metabolic alkalosis.</jats:p>