Sodium and potassium balance depends on αENaC expression in connecting tubule.

Détails

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Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_FDBFEE3BAC47
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Sodium and potassium balance depends on αENaC expression in connecting tubule.
Périodique
Journal of the American Society of Nephrology : Jasn
Auteur(s)
Christensen B.M., Perrier R., Wang Q., Zuber A.M., Maillard M., Mordasini D., Malsure S., Ronzaud C., Stehle J.C., Rossier B.C., Hummler E.
ISSN
1533-3450
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
21
Numéro
11
Pages
1942-1951
Langue
anglais
Résumé
Mutations in α, β, or γ subunits of the epithelial sodium channel (ENaC) can downregulate ENaC activity and cause a severe salt-losing syndrome with hyperkalemia and metabolic acidosis, designated pseudohypoaldosteronism type 1 in humans. In contrast, mice with selective inactivation of αENaC in the collecting duct (CD) maintain sodium and potassium balance, suggesting that the late distal convoluted tubule (DCT2) and/or the connecting tubule (CNT) participates in sodium homeostasis. To investigate the relative importance of ENaC-mediated sodium absorption in the CNT, we used Cre-lox technology to generate mice lacking αENaC in the aquaporin 2-expressing CNT and CD. Western blot analysis of microdissected cortical CD (CCD) and CNT revealed absence of αENaC in the CCD and weak αENaC expression in the CNT. These mice exhibited a significantly higher urinary sodium excretion, a lower urine osmolality, and an increased urine volume compared with control mice. Furthermore, serum sodium was lower and potassium levels were higher in the genetically modified mice. With dietary sodium restriction, these mice experienced significant weight loss, increased urinary sodium excretion, and hyperkalemia. Plasma aldosterone levels were significantly elevated under both standard and sodium-restricted diets. In summary, αENaC expression within the CNT/CD is crucial for sodium and potassium homeostasis and causes signs and symptoms of pseudohypoaldosteronism type 1 if missing.
Mots-clé
Aldosterone/blood, Animals, Aquaporin 2/metabolism, Epithelial Sodium Channel/genetics, Epithelial Sodium Channel/metabolism, Female, Homeostasis/physiology, Kidney Cortex/cytology, Kidney Cortex/drug effects, Kidney Tubules/cytology, Kidney Tubules/drug effects, Kidney Tubules, Collecting/cytology, Kidney Tubules, Collecting/drug effects, Male, Mice, Mice, Knockout, Mice, Transgenic, Potassium/metabolism, Sodium/metabolism, Sodium, Dietary/pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/11/2010 14:21
Dernière modification de la notice
20/08/2019 16:28
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