Reducing [alpha]ENaC expression in the kidney connecting tubule induces pseudohypoaldosteronism type 1 symptoms during K+ loading

• Published in: American journal of physiology. Renal physiology 2016-02, Vol.310 (4), p.F300
• Main Authors: Poulsen, Søren Brandt, Praetorius, Jeppe, Damkier, Helle H, Miller, Lance, Nelson, Raoul D, Hummler, Edith, Christensen, Birgitte Mønster
• Format: Article
• Language: English
• Subjects: Diet; Homeostasis; Kidneys; Phosphorylation; Rodents
• ISSN: 1931-857X; 1522-1466

Genetic inactivation of the epithelial Na... channel α-subunit (αENaC) in the renal collecting duct (CD) does not interfere with Na... and K... homeostasis in mice. However, inactivation in the CD and a part of the connecting tubule (CNT) induces autosomal recessive pseudohypoaldosteronism type 1 (PHA-1) symptoms in subjects already on a standard diet. In the present study, we further examined the importance of αENaC in the CNT. Knockout mice with αENaC deleted primarily in a part of the CNT (CNT-KO) were generated using Scnn1a... mice and Atp6v1b1:Cre mice. With a standard diet, plasma Na... concentration ([Na...]) and [K...], and urine Na... and K... output were unaffected. Seven days of Na... restriction (0.01% Na...) led to a higher urine Na... output only on days 3-5, and after 7 days plasma [Na...] and [K...] were unaffected. In contrast, the CNT-KO mice were highly susceptible to a 2-day 5% K... diet and showed lower food intake and relative body weight, lower plasma [Na...], higher fractional excretion (FE) of Na..., higher plasma [K...], and lower FE of K... The higher FE of Na... coincided with lower abundance and phosphorylation of the Na...-Cl... cotransporter. In conclusion, reducing ENaC expression in the CNT induces clear PHA-1 symptoms during high dietary K... loading. (ProQuest: ... denotes formulae/symbols omitted.)