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

Malsure, Sumedha; Wang, Qing; Charles, Roch-Philippe; Sergi, Chloe; Perrier, Romain; Christensen, Birgitte Mønster; Maillard, Marc; Rossier, Bernard C; Hummler, Edith (2014). Colon-specific deletion of epithelial sodium channel causes sodium loss and aldosterone resistance. Journal of the American Society of Nephrology, 25(7), pp. 1453-1464. Lippincott Williams & Wilkins 10.1681/ASN.2013090936

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Charles, Roch-Philippe

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1046-6673

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Roch-Philippe Charles

Date Deposited:

16 Mar 2015 13:36

Last Modified:

11 Nov 2015 13:41

Publisher DOI:

10.1681/ASN.2013090936

PubMed ID:

24480829

URI:

https://boris.unibe.ch/id/eprint/64732

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