Sodium self-inhibition of human epithelial sodium channel: selectivity and affinity of the extracellular sodium sensing site

Détails

ID Serval
serval:BIB_87EAF9EE0871
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Sodium self-inhibition of human epithelial sodium channel: selectivity and affinity of the extracellular sodium sensing site
Périodique
American Journal of Physiology. Renal Physiology
Auteur(s)
Bize  V., Horisberger  J. D.
ISSN
0363-6127 (Print)
Statut éditorial
Publié
Date de publication
10/2007
Volume
293
Numéro
4
Pages
F1137-46
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct
Résumé
The epithelial Na(+) channel (ENaC) is present in the apical membrane of "tight" epithelia in the distal nephron, distal colon, and airways. Its activity controls the rate of transepithelial sodium transport. Among other regulatory factors, ENaC activity is controlled by the concentration of extracellular Na(+), a phenomenon named self-inhibition. The molecular mechanism by which extracellular Na(+) concentration is detected is not known. To investigate the properties of the extracellular Na(+) sensing site, we studied the effects of extracellular cations on steady-state amiloride-sensitive outward currents in Na(+)-loaded oocytes expressing human ENaC and compared them with self-inhibition of inward current after fast solution changes. About half of the inhibition of outward Na(+) currents was due to self-inhibition itself and the rest might be attributed to conduction site saturation. Self-inhibition by extracellular Li(+) was similar to that of Na(+) except for slightly slower kinetics. Ionic selectivity of the inhibition for steady-state outward current was Na(+) > or = Li(+) > K(+). We estimated an apparent inhibitory constant (K(I)) of approximately 40 mM for extracellular Na(+) and Li(+) and found no evidence for a voltage dependence of the K(I). Protease treatment induced the expected increase of the amiloride-sensitive current measured in high-Na(+) concentrations which was due, at least in part, to abolition of self-inhibition. These results demonstrate that both self-inhibition and saturation play a significant role in the inhibition of ENaC by extracellular Na(+) and that Na(+) and Li(+) interact in a similar way with the extracellular cation sensing site.
Pubmed
Web of science
Création de la notice
24/01/2008 13:38
Dernière modification de la notice
03/03/2018 19:03
Données d'usage