Aarhus Universitet

Birgitte Mønster Christensen

Colon-Specific Deletion of Epithelial Sodium Channel Causes Sodium Loss and Aldosterone Resistance

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Sumedha Malsure, Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland;
  • ,
  • Qing Wang
  • ,
  • Roch-Philippe Charles
  • ,
  • Chloe Sergi
  • ,
  • Romain Perrier
  • ,
  • Birgitte Mønster Christensen
  • Marc Maillard
  • ,
  • Bernard C Rossier
  • ,
  • Edith Hummler
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.
OriginalsprogEngelsk
TidsskriftJournal of the American Society of Nephrology
ISSN1046-6673
DOI
StatusAccepteret/In press - 30 jan. 2014

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