Identification of a highly conserved sequence at the N-terminus of the epithelial Na+ channel alpha subunit involved in gating

Détails

ID Serval
serval:BIB_9952B5D6D49C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Identification of a highly conserved sequence at the N-terminus of the epithelial Na+ channel alpha subunit involved in gating
Périodique
Pflügers Archiv : European Journal of Physiology
Auteur(s)
Grunder  S., Jaeger  N. F., Gautschi  I., Schild  L., Rossier  B. C.
ISSN
0031-6768
Statut éditorial
Publié
Date de publication
10/1999
Peer-reviewed
Oui
Volume
438
Numéro
5
Pages
709-715
Résumé
The epithelial Na+ channel (ENaC) is responsible for Na+ reabsorption in aldosterone target tissues such as distal nephron and colon. ENaC is a heterotetramer composed of three homologous subunits, alpha, beta, and gammaENaC. Mutations leading to loss of function or reduced channel activity have been identified in all three subunits in patients with pseudohypoaldosteronism type-1. One missense mutation substituting a glycine (G95S) which is completely conserved throughout the gene family reduced ENaC open probability, Po. In this study we have performed systematic alanine substitutions of 28 residues of alphaENaC encompassing the glycine (G95). This screen identified a stretch of ten consecutive amino acids (alphaT92-alphaC101) which, when mutated, lead to a decrease in Na+ current (I(Na)) expressed with no significant changes in channel surface expression. This inhibitory effect was strongest for G95 and for two additional highly conserved amino acids--H94 and R98. The R98A mutant led to an important reduction in channel Po with no change in single-channel conductance, indicating that the segment encompassing H94, G95 and R98 is involved in modulation of channel gating kinetics.
Mots-clé
Alanine Amino Acid Sequence Animals *Conserved Sequence Electric Conductivity Epithelium/chemistry Female Gene Expression Glycine Humans Ion Channel Gating/*physiology Molecular Sequence Data Mutagenesis Oocytes/metabolism Point Mutation Rats Sequence Alignment Sodium Channels/*chemistry/genetics/*physiology Xenopus laevis
Pubmed
Web of science
Création de la notice
24/01/2008 14:00
Dernière modification de la notice
20/08/2019 16:00
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