Reducing αENaC expression in kidney connecting tubule induces pseudohypoaldosteronism type 1 symptoms during K+ loading

Søren Brandt Poulsen, Jeppe Praetorius, Helle H Damkier, Lance Miller, Raoul D Nelson, Edith Hummler, Birgitte M Christensen

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

Abstract

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 lox/lox mice and Atp6v1b1::Cremice. 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.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology: Renal Physiology
Vol/bind310
Nummer4
Sider (fra-til)F300-F310
Antal sider11
ISSN1931-857X
DOI
StatusUdgivet - 2016

Fingeraftryk

Dyk ned i forskningsemnerne om 'Reducing αENaC expression in kidney connecting tubule induces pseudohypoaldosteronism type 1 symptoms during K+ loading'. Sammen danner de et unikt fingeraftryk.

Citationsformater