Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC Knockout.

Détails

ID Serval
serval:BIB_E4F46D8241F3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC Knockout.
Périodique
Journal of the American Society of Nephrology
Auteur(s)
Boscardin E., Perrier R., Sergi C., Maillard M.P., Loffing J., Loffing-Cueni D., Koesters R., Rossier B.C., Hummler E.
ISSN
1533-3450 (Electronic)
ISSN-L
1046-6673
Statut éditorial
Publié
Date de publication
03/2018
Peer-reviewed
Oui
Volume
29
Numéro
3
Pages
977-990
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the αENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of αENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa <sup>+</sup> )/low potassium (LK <sup>+</sup> ) rescue diet. Rescue reflects activation of NCC, which is suppressed at baseline by elevated plasma potassium concentration. In this study, we investigated the role of the γENaC subunit in the PHA-I phenotype. Nephron-specific γENaC knockout mice also presented with salt-wasting syndrome and severe hyperkalemia. Unlike mice lacking αENaC or βΕΝaC, an HNa <sup>+</sup> /LK <sup>+</sup> diet did not normalize plasma potassium (K <sup>+</sup> ) concentration or increase NCC activation. However, when K <sup>+</sup> was eliminated from the diet at the time that γENaC was deleted, plasma K <sup>+</sup> concentration and NCC activity remained normal, and progressive weight loss was prevented. Loss of the late distal convoluted tubule, as well as overall reduced βENaC subunit expression, may be responsible for the more severe hyperkalemia. We conclude that plasma K <sup>+</sup> concentration becomes the determining and limiting factor in regulating NCC activity, regardless of Na <sup>+</sup> balance in γENaC-deficient mice.
Mots-clé
Animals, Chelating Agents/therapeutic use, Dietary Supplements, Epithelial Sodium Channels/genetics, Hyperkalemia/blood, Hyperkalemia/drug therapy, Hyperkalemia/genetics, Mice, Mice, Knockout, Nephrons, Polystyrenes/therapeutic use, Potassium/blood, Potassium, Dietary/administration & dosage, Pseudohypoaldosteronism/blood, Pseudohypoaldosteronism/genetics, Sodium, Dietary/administration & dosage, Solute Carrier Family 12, Member 3/metabolism, Na+/Cl- co-transporter, Pseudohypoaldosteronism, SPAK, epithelial sodium channel, thiazide-sensitive
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/02/2018 20:18
Dernière modification de la notice
24/09/2019 5:11
Données d'usage