Intracellular thiol-mediated modulation of epithelial sodium channel activity.

Détails

ID Serval
serval:BIB_F3F94846CFDF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Intracellular thiol-mediated modulation of epithelial sodium channel activity.
Périodique
Journal of Biological Chemistry
Auteur(s)
Kellenberger S., Gautschi I., Pfister Y., Schild L.
ISSN
0021-9258[print], 0021-9258[linking]
Statut éditorial
Publié
Date de publication
2005
Volume
280
Numéro
9
Pages
7739-7747
Langue
anglais
Résumé
The epithelial sodium channel ENaC is physiologically important in the kidney for the regulation of the extracellular fluid volume, and in the lungs for the maintenance of the appropriate airway surface liquid volume that lines the pulmonary epithelium. Besides the regulation of ENaC by hormones, intracellular factors such as Na(+) ions, pH, or Ca(2+) are responsible for fast adaptive responses of ENaC activity to changes in the intracellular milieu. In this study, we show that ENaC is rapidly and reversibly inhibited by internal sulfhydryl-reactive molecules such as methanethiosulfonate derivatives of different sizes, the metal cations Cd(2+) and Zn(2+), or copper(II) phenanthroline, a mild oxidizing agent that promotes the formation of disulfide bonds. At the single channel level, these agents applied intracellularly induce the appearance of long channel closures, suggesting an effect on ENaC gating. The intracellular reducing agent dithiothreitol fully reverses the rundown of ENaC activity in inside-out patches. Our observations suggest that changes in intracellular redox potential modulate ENaC activity and may regulate ENaC-mediated Na(+) transport in epithelia. Finally, substitution experiments reveal that multiple cysteine residues in the amino and carboxyl termini of ENaC subunits are responsible for this thiol-mediated inhibition of ENaC.
Mots-clé
Animals, Cadmium/chemistry, Calcium/chemistry, Cell Membrane/metabolism, Chelating Agents/pharmacology, Copper/chemistry, Cysteine/chemistry, Dithiothreitol/pharmacology, Edetic Acid/pharmacology, Egtazic Acid/analogs & derivatives, Egtazic Acid/pharmacology, Electrophysiology, Epithelial Sodium Channel, Female, Hydrogen-Ion Concentration, Ions, Mesylates/chemistry, Models, Biological, Mutagenesis, Site-Directed, Oocytes/metabolism, Oxygen/chemistry, Protein Conformation, Protein Structure, Tertiary, RNA, Complementary/metabolism, Sodium/chemistry, Sodium Channels/metabolism, Sodium Channels/physiology, Sulfhydryl Compounds/metabolism, Time Factors, Xenopus laevis, Zinc/chemistry
Pubmed
Web of science
Création de la notice
24/01/2008 13:45
Dernière modification de la notice
03/03/2018 22:43
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