The AE4 transporter mediates kidney acid-base sensing
Helga Vitzthum, Marianne Koch, Leya Eckermann, Samuel L. Svendsen, Peder Berg, Christian A. Hübner, Carsten A. Wagner, Jens Leipziger, Catherine Meyer‐Schwesinger, Heimo Ehmke
Abstract
Abstract The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which secrete acid or base into the urine. How these cells sense acid-base disturbances is a long-standing question. Intercalated cells exclusively express the Na + -dependent Cl − /HCO 3 − exchanger AE4 ( Slc4a9 ). Here we show that AE4-deficient mice exhibit a major dysregulation of acid-base balance. By combining molecular, imaging, biochemical and integrative approaches, we demonstrate that AE4-deficient mice are unable to sense and appropriately correct metabolic alkalosis and acidosis. Mechanistically, a lack of adaptive base secretion via the Cl − /HCO 3 − exchanger pendrin ( Slc26a4 ) is the key cellular cause of this derailment. Our findings identify AE4 as an essential part of the renal sensing mechanism for changes in acid-base status.