Impaired regulation of renal K+ elimination in the sgk1-knockout mouse.
Serum- and glucocorticoid-regulated kinase 1 (Sgk1) contributes to Na+ reabsorption in the aldosterone-sensitive distal nephron. Sgk1-knockout (sgk1-/-) and littermate wild-type mice (sgk1+/+) were used to test the importance of Sgk1 in renal elimination of K+ . Intravenous application of K+ load under anesthesia increased plasma K+ concentration by 1.3 to 1.4 mM in both sgk1-/- (n = 6) and sgkl+/+ (n = 7) mice. However, the increase of absolute and fractional renal K+ excretion observed in sgk1+/+ was significantly blunted in sgk1-/- animals. Both groups of mice decreased or increased renal K+ excretion to a similar extent after a low (<0.03%) or high (5%) K+ diet for 6 d, respectively. In sgk1+/+, plasma K+ concentration was not significantly modified by either high or low K+ diet. In sgk1-/-, however, high K+ diet enhanced plasma K+ concentration by about 1.6 mM, despite an excessive increase of plasma aldosterone concentration reaching values about sixfold higher than in sgk1+/+. Electrophysiological and immunohistochemical studies under high K+ diet indicated that reduced epithelial Na+ channel ENaC and/or Na+/K+-ATPase activity in the aldosterone-sensitive distal nephron accounted for the impaired response in sgk1-/- and that an enhanced apical abundance of renal outer medullary K+ channel ROMK partly compensated for the defect. The acute and chronic regulation of renal K+ elimination involves Sgk1.
Huang
Dan Yang
DY
Department of Pharmacology, University of Tübingen, Germany.
Wulff
Peer
P
Völkl
Harald
H
Loffing
Johannes
J
Richter
Kerstin
K
Kuhl
Dietmar
D
Lang
Florian
F
Vallon
Volker
V
D000818:Animals; D005260:Female; D017874:Immediate-Early Proteins; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins; D011188:Potassium / Q000008:administration & dosage / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D011188:Potassium; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases