The epithelial sodium channel (ENaC) is of fundamental importance in the control of sodium fluxes in epithelial cells. Modulation of sodium reabsorption through the distal nephron ENaC is an important component in the overall control of sodium balance, blood volume and thereby of blood pressure. This is clearly demonstrated by rare genetic disorders of sodium-channel activity (Liddle's syndrome and pseudohypoaldosteronism type 1), associated with contrasting effects on blood pressure. The mineralocorticoid aldosterone is a well-established modulator of sodium-channel activity. Considerable insight has now been gained into the intracellular signalling pathways linking aldosterone-mediated changes in gene transcription with changes in ion transport. Activating pathways include aldosterone-induced proteins and especially the serum- and glucocorticoid-inducible kinase (SGK) and the small G-protein, K-Ras 2A. Targeting of the ENaC for endocytosis and degradation is now emerging as a major mechanism for the down-regulation of channel activity. Several proteins acting in concert are an intrinsic part of this process but Nedd4 (neural precursor cell expressed developmentally down-regulated 4) is of central importance. Other mechanisms known to interact with ENaC and affect sodium transport include channel-activating protease 1 (CAP-1), a membrane-anchored protein, and the cystic fibrosis transmembrane regulator. The implications of research on accessory factors controlling ENaC activity are wide-ranging. Understanding cellular mechanisms controlling ENaC activity may provide a more detailed insight not only of ion-channel abnormalities in cystic fibrosis but also of the link between abnormal renal sodium transport and essential hypertension.
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Review Article|
April 01 2003
Regulation of the epithelial sodium channel by accessory proteins
Kelly GORMLEY;
Kelly GORMLEY
∗Division of Neurosciences, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, U.K.,
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Yanbin DONG;
Yanbin DONG
∗Division of Neurosciences, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, U.K.,
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Giuseppe A. SAGNELLA
Giuseppe A. SAGNELLA
1
†Blood Pressure Unit, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, U.K.
1To whom correspondence should be addressed (e-mail g.sagnella@sghms.ac.uk).
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Publisher: Portland Press Ltd
Received:
September 02 2002
Revision Received:
November 27 2002
Accepted:
December 03 2002
Accepted Manuscript online:
December 03 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 371 (1): 1–14.
Article history
Received:
September 02 2002
Revision Received:
November 27 2002
Accepted:
December 03 2002
Accepted Manuscript online:
December 03 2002
Citation
Kelly GORMLEY, Yanbin DONG, Giuseppe A. SAGNELLA; Regulation of the epithelial sodium channel by accessory proteins. Biochem J 1 April 2003; 371 (1): 1–14. doi: https://doi.org/10.1042/bj20021375
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