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1 Physiology, Dartmouth School of Medicine, Lebanon, New Hampshire, United States
2 Physiology and Biophysics, Weill Medical College of Cornell U., New York, New York, United States
3 Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire, United States
* To whom correspondence should be addressed. E-mail: lgpalm{at}med.cornell.edu.
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 Na+ channel (ENaC) protein. Neither SGK1-/- mice nor paired SGK1+/+ animals expressed detectable channel activity, measured as amiloride-sensitive whole-current (INa), under control conditions with standard chow. Administration of aldosterone (0.5 µg/hour 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 
ENaC, was more pronounced in the 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 did the wild-type mice. Under these conditions, INa was enhanced in the SGK1-/- (94 ±14 pA/cell) compared with SGK+/+ (23± 5 pA/cell). Despite the larger currents, the ratio of cleaved/full length ENaC was lower in the knock-out animals. The mice also expressed a smaller amount of the 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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