The contact region between three domains of the extracellular loop of ASIC1a is critical for channel function.

Détails

Ressource 1Télécharger: BIB_C46FFB5A7D3B.P001.pdf (4135.37 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_C46FFB5A7D3B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The contact region between three domains of the extracellular loop of ASIC1a is critical for channel function.
Périodique
Journal of Biological Chemistry
Auteur⸱e⸱s
Bargeton B., Kellenberger S.
ISSN
1083-351X[electronic], 0021-9258[linking]
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
285
Numéro
18
Pages
13816-13826
Langue
anglais
Résumé
Acid-sensing ion channels are members of the epithelial Na(+) channel/degenerin family. They are neuronal nonvoltage-gated Na(+) channels that are activated by extracellular acidification. In this study, we investigated the role of a highly conserved region of the extracellular part of ASIC1a that forms the contact between the finger domain, the adjacent beta-ball, and the upper palm domain in ASIC1a. The finger domain contributes to the pH-dependent gating and is linked via this contact zone to the rest of the protein. We found that mutation to Cys of residues in this region led to decreased channel expression and current amplitudes. Exposure of the engineered Cys residues to Cd(2+) or to charged methane thiosulfonate sulfhydryl reagents further reduced current amplitudes. This current inhibition was not due to changes in acid-sensing ion channel pH dependence or unitary conductance and was likely due to a decrease of the probability of channel opening. For some mutants, the effect of sulfhydryl reagents depended on the pH of exposure in the range 7.4 to 6.8, suggesting that this zone undergoes conformational changes during inactivation. Our study identifies a region in ASIC1a whose integrity is required for normal channel function.
Mots-clé
Animals, Humans, Hydrogen-Ion Concentration, Ion Channel Gating/physiology, Mesylates/chemistry, Mutation, Nerve Tissue Proteins/chemistry, Nerve Tissue Proteins/genetics, Peptide Mapping/methods, Protein Engineering, Protein Structure, Tertiary, Sodium Channels/chemistry, Sodium Channels/genetics, Xenopus laevis
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/03/2010 14:36
Dernière modification de la notice
20/10/2020 14:41
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