The AE4 transporter mediates kidney acid-base sensing.

H Vitzthum, M Koch, L Eckermann, S L Svendsen, P Berg, C A Hübner, C A Wagner, J Leipziger, C Meyer-Schwesinger, H Ehmke

Nature communications 2023 May 26

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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-/HCO3- 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-/HCO3- 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. © 2023. The Author(s).

Citation

H Vitzthum, M Koch, L Eckermann, S L Svendsen, P Berg, C A Hübner, C A Wagner, J Leipziger, C Meyer-Schwesinger, H Ehmke. The AE4 transporter mediates kidney acid-base sensing. Nature communications. 2023 May 26;14(1):3051