Colon-specific deletion of epithelial sodium channel causes sodium loss and aldosterone resistance.
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State: Public
Version: Final published version
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State: Public
Version: author
Serval ID
serval:BIB_6A776DBC5063
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Colon-specific deletion of epithelial sodium channel causes sodium loss and aldosterone resistance.
Journal
Journal of the American Society of Nephrology
ISSN
1533-3450 (Electronic)
ISSN-L
1046-6673
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
25
Number
7
Pages
1453-1464
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
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
Yes
Create date
05/08/2014 18:43
Last modification date
20/10/2020 9:19