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The AE4 transporter mediates kidney acid-base sensing

Author

Listed:
  • H. Vitzthum

    (University Medical Center Hamburg-Eppendorf)

  • M. Koch

    (University Medical Center Hamburg-Eppendorf)

  • L. Eckermann

    (University Medical Center Hamburg-Eppendorf)

  • S. L. Svendsen

    (Aarhus University)

  • P. Berg

    (Aarhus University)

  • C. A. Hübner

    (University Hospital Jena, Friedrich Schiller University)

  • C. A. Wagner

    (University of Zurich
    National Center of Competence in Research NCCR Kidney.CH)

  • J. Leipziger

    (Aarhus University)

  • C. Meyer-Schwesinger

    (University Medical Center Hamburg-Eppendorf)

  • H. Ehmke

    (University Medical Center Hamburg-Eppendorf
    Partner Site Hamburg/Kiel/Lübeck)

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−/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.

Suggested 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, 2023. "The AE4 transporter mediates kidney acid-base sensing," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38562-x
    DOI: 10.1038/s41467-023-38562-x
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