Epithelial Na+ channel activation and processing in mice lacking SGK1

G Fejes-Toth, G Frindt… - American Journal of …, 2008 - journals.physiology.org
G Fejes-Toth, G Frindt, A Náray-Fejes-Tóth, LG Palmer
American Journal of Physiology-Renal Physiology, 2008journals.physiology.org
Amiloride-sensitive Na+ channel activity was examined in the cortical collecting ducts of a
mouse line (SGK1−/−) deficient in the serum-and glucocorticoid-dependent protein kinase
SGK1. This activity was correlated with changes in renal Na handling and in the maturation
of epithelial Na+ channel (ENaC) protein. Neither SGK1−/− mice nor paired SGK1+/+
animals expressed detectable channel activity, measured as amiloride-sensitive whole-cell
current (I Na), under control conditions with standard chow. Administration of aldosterone …
Amiloride-sensitive Na+ channel activity was examined in the cortical collecting ducts of a mouse line (SGK1−/−) deficient in the serum- and glucocorticoid-dependent protein kinase SGK1. This activity was correlated with changes in renal Na handling and in the maturation of epithelial Na+ channel (ENaC) protein. Neither SGK1−/− mice nor paired SGK1+/+ animals expressed detectable channel activity, measured as amiloride-sensitive whole-cell current (INa), under control conditions with standard chow. Administration of aldosterone (0.5 μg/h via osmotic minipump for 7 days) increased INa to a similar extent in SGK1+/+ (378 ± 61 pA/cell at −100 mV) and in SGK1−/− (350 ± 57 pA/cell) animals. However, the maturation of ENaC, assessed as the ratio of cleaved to full-length forms of γ-ENaC, was more pronounced in SGK+/+ mice. The SGK1−/− animals exhibited a salt-wasting phenotype when kept on a low-Na diet for up to 2 days, losing significantly more Na in the urine than wild-type mice. Under these conditions, INa was enhanced more in SGK1−/− (94 ± 14 pA/cell) than in SGK+/+ (23 ± 5 pA/cell) genotypes. Despite the larger currents, the ratio of cleaved to full-length γ-ENaC was lower in the knockout animals. The mice also expressed a smaller amount of Na+-Cl cotransporter protein under Na-depleted conditions. These results indicated that SGK1 is essential for optimal processing of ENaC but is not required for activation of the channel by aldosterone.
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