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

Details

Serval ID
serval:BIB_70B5630A042A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
An external site controls closing of the epithelial Na+ channel ENaC.
Journal
Journal of Physiology
Author(s)
Kellenberger S., Gautschi I., Schild L.
ISSN
0022-3751[print], 0022-3751[linking]
Publication state
Published
Issued date
2002
Volume
543
Number
Pt 2
Pages
413-424
Language
english
Abstract
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.
Keywords
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
Create date
24/01/2008 12:45
Last modification date
20/08/2019 14:29
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