Colon-specific deletion of epithelial sodium channel causes sodium loss and aldosterone resistance.

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Etat: Public
Version: Final published version
Document(s) secondaire(s)
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ID Serval
serval:BIB_6A776DBC5063
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Colon-specific deletion of epithelial sodium channel causes sodium loss and aldosterone resistance.
Périodique
Journal of the American Society of Nephrology
Auteur(s)
Malsure S., Wang Q., Charles R.P., Sergi C., Perrier R., Christensen B.M., Maillard M., Rossier B.C., Hummler E.
ISSN
1533-3450 (Electronic)
ISSN-L
1046-6673
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
25
Numéro
7
Pages
1453-1464
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
Aldosterone promotes electrogenic sodium reabsorption through the amiloride-sensitive epithelial sodium channel (ENaC). Here, we investigated the importance of ENaC and its positive regulator channel-activating protease 1 (CAP1/Prss8) in colon. Mice lacking the αENaC subunit in colonic superficial cells (Scnn1a(KO)) were viable, without fetal or perinatal lethality. Control mice fed a regular or low-salt diet had a significantly higher amiloride-sensitive rectal potential difference (∆PDamil) than control mice fed a high-salt diet. In Scnn1a(KO) mice, however, this salt restriction-induced increase in ∆PDamil did not occur, and the circadian rhythm of ∆PDamil was blunted. Plasma and urinary sodium and potassium did not change with regular or high-salt diets or potassium loading in control or Scnn1a(KO) mice. However, Scnn1a(KO) mice fed a low-salt diet lost significant amounts of sodium in their feces and exhibited high plasma aldosterone and increased urinary sodium retention. Mice lacking the CAP1/Prss8 in colonic superficial cells (Prss8(KO)) were viable, without fetal or perinatal lethality. Compared with controls, Prss8(KO) mice fed regular or low-salt diets exhibited significantly reduced ∆PDamil in the afternoon, but the circadian rhythm was maintained. Prss8(KO) mice fed a low-salt diet also exhibited sodium loss through feces and higher plasma aldosterone levels. Thus, we identified CAP1/Prss8 as an in vivo regulator of ENaC in colon. We conclude that, under salt restriction, activation of the renin-angiotensin-aldosterone system in the kidney compensated for the absence of ENaC in colonic surface epithelium, leading to colon-specific pseudohypoaldosteronism type 1 with mineralocorticoid resistance without evidence of impaired potassium balance.
Pubmed
Web of science
Open Access
Oui
Création de la notice
05/08/2014 18:43
Dernière modification de la notice
20/08/2019 15:25
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