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Birgitte Mønster Christensen

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

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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 already on a standard diet. In the present study, we further examined the importance of αENaC in the CNT. Knock-out mice with αENaC deleted primarily in a part of the CNT (CNT-KO) were generated using Scnn1a(lox/lox) mice and Atp6v1b1::Cre mice. On a standard diet, plasma [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 day 3-5, and after 7 days plasma [Na(+)] and [K(+)] were unaffected. By 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, NCC. In conclusion, reducing ENaC expression in CNT induces clear PHA-1 symptoms during high dietary K(+) loading.

TidsskriftAmerican Journal of Physiology: Renal Physiology
Sider (fra-til)F300-F310
Antal sider11
StatusUdgivet - 2016

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