Epithelial Na+ channel activation and processing in mice lacking SGK1

Am J Physiol Renal Physiol. 2008 Jun;294(6):F1298-305. doi: 10.1152/ajprenal.00579.2007. Epub 2008 Apr 2.

Abstract

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 (0.5 microg/h via osmotic minipump for 7 days) increased I(Na) 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 gamma-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, I(Na) 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 gamma-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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aldosterone / metabolism
  • Animals
  • Epithelial Sodium Channels / metabolism*
  • Female
  • Heterozygote
  • Homozygote
  • Hyperaldosteronism / genetics
  • Hyperaldosteronism / metabolism
  • Hyperaldosteronism / physiopathology*
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / metabolism*
  • Kidney Tubules, Collecting / metabolism*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Natriuresis / physiology
  • Pregnancy
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Sodium, Dietary / pharmacokinetics*

Substances

  • Epithelial Sodium Channels
  • Immediate-Early Proteins
  • Scnn1g protein, mouse
  • Sodium, Dietary
  • Aldosterone
  • Protein-Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase