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 and H. Ehmke ()
Additional contact information
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
J. Leipziger: Aarhus University
C. Meyer-Schwesinger: University Medical Center Hamburg-Eppendorf
H. Ehmke: University Medical Center Hamburg-Eppendorf

Nature Communications, 2023, vol. 14, issue 1, 1-9

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−/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.

Date: 2023
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-38562-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38562-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-38562-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().