title: SGK1-dependent ENaC processing and trafficking in mice with high dietary K intake and elevated aldosterone.
abstract: We examined renal Na and K transporters in mice with deletions in the gene encoding the aldosterone-induced protein SGK1. The knockout mice were hyperkalemic, and had altered expression of the subunits of the epithelial Na channel (ENaC). The kidneys showed decreased expression of the cleaved forms of the γENaC subunit, and the fully glycosylated form of the βENaC subunits when animals were fed a high-K diet. Knockout animals treated with exogenous aldosterone also had reduced subunit processing and diminished surface expression of βENaC and γENaC. Expression of the three upstream Na transporters NHE3, NKCC2, and NCC was reduced in both wild-type and knockout mice in response to K loading. The activity of ENaC measured as whole cell amiloride-sensitive current (INa) in principal cells of the cortical collecting duct (CCD) was minimal under control conditions but was increased by a high-K diet to a similar extent in knockout and wild-type animals. INain the connecting tubule also increased similarly in the two genotypes in response to exogenous aldosterone administration. The activities of both ROMK channels in principal cells and BK channels in intercalated cells of the CCD were unaffected by the deletion of SGK1. Acute treatment of animals with amiloride produced similar increases in Na excretion and decreases in K excretion in the two genotypes. The absence of changes in ENaC activity suggests compensation for decreased surface expression. Altered K balance in animals lacking SGK1 may reflect defects in ENaC-independent K excretion.
authors.affiliation: Department of Physiology and Biophysics, Weill-Cornell Medical College, New York, New York.|Department of Physiology, Harbin Medical University, Harbin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Physiology and Biophysics, Weill-Cornell Medical College, New York, New York.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Frindt
authors.affiliation: Department of Cardiology, Vascular Medicine and Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Florian
authors.identifier: 0000-0003-2962-1540
authors.initials: F
authors.lastname: Lang
authors.affiliation: Institute for Molecular and Cellular Cognition, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; and.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kuhl
authors.affiliation: Departments of Medicine and Pharmacology, University of California San Diego and Veterans Affairs San Diego Healthcare System, San Diego, California.
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
authors.affiliation: Department of Physiology and Biophysics, Weill-Cornell Medical College, New York, New York; lgpalm@med.cornell.edu.
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Palmer
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000584:Amiloride / Q000378:metabolism*; D000818:Animals; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D018345:Mice, Knockout; D011188:Potassium / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D012982:Sodium, Dietary / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000450:Aldosterone; D000584:Amiloride; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D011188:Potassium; D017346:Protein Serine-Threonine Kinases; D012982:Sodium, Dietary; D000099184:Serum-Glucocorticoid Regulated Kinases
keywords: aldosterone-induced protein; amiloride-sensitive channels; connecting tubule; cortical collecting duct; surface expression