The epithelial sodium channel and the control of sodium balance.

Détails

ID Serval
serval:BIB_F9F817B1C82F
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Titre
The epithelial sodium channel and the control of sodium balance.
Périodique
Biochimica et Biophysica Acta-Molecular Basis of Disease
Auteur(s)
Schild L.
ISSN
0925-4439
ISSN-L
1879-260X
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
1802
Numéro
12
Pages
1159-1165
Langue
anglais
Résumé
Studies aiming at the elucidation of the genetic basis of rare monogenic forms of hypertension have identified mutations in genes coding for the epithelial sodium channel ENaC, for the mineralocorticoid receptor, or for enzymes crucial for the synthesis of aldosterone. These genetic studies clearly demonstrate the importance of the regulation of Na(+) absorption in the aldosterone-sensitive distal nephron (ASDN), for the maintenance of the extracellular fluid volume and blood pressure. Recent studies aiming at a better understanding of the cellular and molecular basis of ENaC-mediated Na(+) absorption in the distal part of nephron, have essentially focused on the regulation ENaC activity and on the aldosterone-signaling cascade. ENaC is a constitutively open channel, and factors controlling the number of active channels at the cell surface are likely to have profound effects on Na(+) absorption in the ASDN, and in the amount of Na(+) that is excreted in the final urine. A number of membrane-bound proteases, kinases, have recently been identified that increase ENaC activity at the cell surface in heterologous expressions systems. Ubiquitylation is a general process that regulates the stability of a variety of target proteins that include ENaC. Recently, deubiquitylating enzymes have been shown to increase ENaC activity in heterologous expressions systems. These regulatory mechanisms are likely to be nephron specific, since in vivo studies indicate that the adaptation of the renal excretion of Na(+) in response to Na(+) diet occurs predominantly in the early part (the connecting tubule) of the ASDN. An important work is presently done to determine in vivo the physiological relevance of these cellular and molecular mechanisms in regulation of ENaC activity. The contribution of the protease-dependent ENaC regulation in mediating Na(+) absorption in the ASDN is still not clearly understood. The signaling pathway that involves ubiquitylation of ENaC does not seem to be absolutely required for the aldosterone-mediated control of ENaC. These in vivo physiological studies presently constitute a major challenge for our understanding of the regulation of ENaC to maintain the Na(+) balance.
Mots-clé
Aldosterone/genetics, Aldosterone/metabolism, Animals, Blood Pressure/genetics, Epithelial Sodium Channel/genetics, Epithelial Sodium Channel/metabolism, Humans, Hypertension/genetics, Hypertension/urine, Nephrons/metabolism, Receptors, Mineralocorticoid/genetics, Receptors, Mineralocorticoid/metabolism, Signal Transduction/genetics, Sodium/urine, Ubiquitination/genetics, Water-Electrolyte Balance
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/02/2011 14:13
Dernière modification de la notice
20/08/2019 17:25
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