Epithelial Na+ channel activation and processing in mice lacking SGK1.
Geza Fejes-Tóth1, Gustavo Frindt, Aniko Náray-Fejes-Tóth
1Dept. of Physiology, Dartmouth School of Medicine, Lebanon, NH, USA.
American Journal of Physiology. Renal Physiology
|April 4, 2008
Summary
Serum- and glucocorticoid-dependent protein kinase 1 (SGK1) is crucial for epithelial sodium channel (ENaC) maturation and proper renal sodium handling. SGK1 deficiency impairs ENaC processing, leading to salt wasting despite normal aldosterone response.
Area of Science:
- Nephrology
- Molecular Biology
- Physiology
Background:
- Epithelial sodium channels (ENaC) are critical for regulating sodium balance in the kidneys.
- Serum- and glucocorticoid-dependent protein kinase 1 (SGK1) is implicated in ENaC function, but its precise role in channel maturation and aldosterone responsiveness is not fully understood.
Purpose of the Study:
- To investigate the role of SGK1 in amiloride-sensitive sodium channel activity, renal sodium handling, and ENaC maturation in mice.
- To determine if SGK1 is required for aldosterone-induced ENaC activation.
Main Methods:
- Examined amiloride-sensitive Na(+) channel activity (I(Na)) in cortical collecting ducts of SGK1 knockout (SGK1(-/-)) and wild-type (SGK1(+/+)) mice.
- Assessed ENaC maturation by measuring the ratio of cleaved to full-length gamma-ENaC.
- Evaluated renal sodium handling and Na(+)-Cl(-) cotransporter expression under low-sodium diet conditions.
Main Results:
- Aldosterone increased I(Na) similarly in both SGK1(+/+) and SGK1(-/-) mice, indicating SGK1 is not required for aldosterone-induced channel activation.
- SGK1(-/-) mice showed impaired ENaC maturation (lower cleaved to full-length gamma-ENaC ratio) compared to wild-type mice.
- SGK1(-/-) mice exhibited a salt-wasting phenotype with increased urinary sodium loss and enhanced I(Na) under low-sodium diet, despite reduced ENaC maturation.
Conclusions:
- SGK1 is essential for the optimal processing and maturation of ENaC, but not for its activation by aldosterone.
- SGK1 plays a critical role in maintaining renal sodium balance, particularly under conditions of sodium depletion.
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