The AE4 transporter mediates kidney acid-base sensing.
H Vitzthum1, M Koch1, L Eckermann1
1Center for Experimental Medicine, Institute of Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Nature Communications
|May 26, 2023
Summary
The kidney
Area of Science:
- Nephrology
- Physiology
- Molecular Biology
Background:
- The kidney is crucial for maintaining systemic acid-base balance.
- Intercalated cells in the distal nephron regulate acid-base status by secreting ions.
- The sensing mechanism of these cells for acid-base disturbances remains unclear.
Purpose of the Study:
- To investigate the role of the Na+-dependent Cl-/HCO3- exchanger AE4 (Slc4a9) in renal acid-base sensing.
- To elucidate the mechanism by which AE4 contributes to acid-base homeostasis.
Main Methods:
- Utilized AE4-deficient mice models.
- Employed molecular, imaging, biochemical, and integrative approaches.
- Assessed acid-base balance regulation in response to metabolic disturbances.
Main Results:
- AE4-deficient mice displayed significant acid-base balance dysregulation.
- These mice were unable to appropriately correct metabolic acidosis and alkalosis.
- A key cellular defect identified was the lack of adaptive base secretion via pendrin (Slc26a4).
Conclusions:
- AE4 is essential for the renal sensing of acid-base status.
- AE4 deficiency impairs the kidney's ability to correct acid-base imbalances.
- Dysfunctional AE4 leads to impaired pendrin-mediated base secretion, causing acid-base derangement.
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