Severe hyperkalemia is rescued by low-potassium diet in renal βENaC-deficient mice.

Détails

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Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_4EC29369905D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Severe hyperkalemia is rescued by low-potassium diet in renal βENaC-deficient mice.
Périodique
Pflugers Archiv
Auteur(s)
Boscardin E., Perrier R., Sergi C., Maillard M., Loffing J., Loffing-Cueni D., Koesters R., Rossier B.C., Hummler E.
ISSN
1432-2013 (Electronic)
ISSN-L
0031-6768
Statut éditorial
Publié
Date de publication
10/2017
Peer-reviewed
Oui
Volume
469
Numéro
10
Pages
1387-1399
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
In adulthood, an induced nephron-specific deficiency of αENaC (Scnn1a) resulted in pseudohypoaldosteronism type 1 (PHA-1) with sodium loss, hyperkalemia, and metabolic acidosis that is rescued through high-sodium/low-potassium (HNa <sup>+</sup> /LK <sup>+</sup> ) diet. In the present study, we addressed whether renal βENaC expression is required for sodium and potassium balance or can be compensated by remaining (α and γ) ENaC subunits using adult nephron-specific knockout (Scnn1b <sup>Pax8/LC1</sup> ) mice. Upon induction, these mice present a severe PHA-1 phenotype with weight loss, hyperkalemia, and dehydration, but unlike the Scnn1a <sup>Pax8/LC1</sup> mice without persistent salt wasting. This is followed by a marked downregulation of STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) and Na <sup>+</sup> /Cl <sup>-</sup> co-transporter (NCC) protein expression and activity. Most of the experimental Scnn1b <sup>Pax8/LC1</sup> mice survived with a HNa <sup>+</sup> /LK <sup>+</sup> diet that partly normalized NCC phosphorylation, but not total NCC expression. Since salt loss was minor, we applied a standard-sodium/LK <sup>+</sup> diet that efficiently rescued these mice resulting in normokalemia and normalization of NCC phosphorylation, but not total NCC expression. A further switch to LNa <sup>+</sup> /standard-K <sup>+</sup> diet induced again a severe PHA-1-like phenotype, but with only transient salt wasting indicating that low-K <sup>+</sup> intake is critical to decrease hyperkalemia in a NCC-dependent manner. In conclusion, while the βENaC subunit plays only a minor role in sodium balance, severe hyperkalemia results in downregulation of NCC expression and activity. Our data demonstrate the importance to primarily correct the hyperkalemia with a low-potassium diet that normalizes NCC activity.
Mots-clé
Animals, Diet, Sodium-Restricted, Epithelial Sodium Channels/metabolism, Hyperkalemia/metabolism, Kidney/metabolism, Mice, Transgenic, Nephrons/metabolism, Phenotype, Potassium/metabolism, Potassium Channels, Inwardly Rectifying/metabolism, Sodium/metabolism, Epithelial sodium channel, Hyperkalemia, Pseudohypoaldosteronism type 1, STE20/SPS1-related proline-alanine-rich protein kinase, Thiazide-sensitive Na+/Cl− co-transporter
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/06/2017 8:46
Dernière modification de la notice
20/08/2019 14:04
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