An external site controls closing of the epithelial Na+ channel ENaC.

Détails

ID Serval
serval:BIB_70B5630A042A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
An external site controls closing of the epithelial Na+ channel ENaC.
Périodique
Journal of Physiology
Auteur(s)
Kellenberger S., Gautschi I., Schild L.
ISSN
0022-3751[print], 0022-3751[linking]
Statut éditorial
Publié
Date de publication
2002
Volume
543
Numéro
Pt 2
Pages
413-424
Langue
anglais
Résumé
Members of the ENaC/degenerin family of ion channels include the epithelial sodium channel (ENaC), acid-sensing ion channels (ASICs) and the nematode Caenorhabditis elegans degenerins. These channels are activated by a variety of stimuli such as ligands (ASICs) and mechanical forces (degenerins), or otherwise are constitutively active (ENaC). Despite their functional heterogeneity, these channels might share common basic mechanisms for gating. Mutations of a conserved residue in the extracellular loop, namely the 'degenerin site' activate all members of the ENaC/degenerin family. Chemical modification of a cysteine introduced in the degenerin site of rat ENaC (betaS518C) by the sulfhydryl reagents MTSET or MTSEA, results in a approximately 3-fold increase in the open probability. This effect is due to an 8-fold shortening of channel closed times and an increase in the number of long openings. In contrast to the intracellular gating domain in the N-terminus which is critical for channel opening, the intact extracellular degenerin site is necessary for normal channel closing, as illustrated by our observation that modification of betaS518C destabilises the channel closed state. The modification by the sulfhydryl reagents is state- and size-dependent consistent with a conformational change of the degenerin site during channel opening and closing. We propose that the intracellular and extracellular modulatory sites act on a common channel gate and control the activity of ENaC at the cell surface.
Mots-clé
Animals, Epithelial Sodium Channel, Female, Ion Channel Gating/physiology, Kinetics, Membrane Potentials/physiology, Mutagenesis, Site-Directed, Oocytes/physiology, Patch-Clamp Techniques, Protein Structure, Quaternary, Protein Structure, Tertiary, Rats, Sodium Channels/chemistry, Sodium Channels/genetics, Structure-Activity Relationship, Xenopus laevis
Pubmed
Web of science
Création de la notice
24/01/2008 13:45
Dernière modification de la notice
20/08/2019 15:29
Données d'usage