On the molecular basis of ion permeation in the epithelial Na+ channel.

Détails

Ressource 1Télécharger: BIB_FD7CDFDF42D0.P001.pdf (362.00 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_FD7CDFDF42D0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
On the molecular basis of ion permeation in the epithelial Na+ channel.
Périodique
Journal of General Physiology
Auteur(s)
Kellenberger S., Hoffmann-Pochon N., Gautschi I., Schneeberger E., Schild L.
ISSN
0022-1295[print], 0022-1295[linking]
Statut éditorial
Publié
Date de publication
1999
Volume
114
Numéro
1
Pages
13-30
Langue
anglais
Résumé
The epithelial Na+ channel (ENaC) is highly selective for Na+ and Li+ over K+ and is blocked by the diuretic amiloride. ENaC is a heterotetramer made of two alpha, one beta, and one gamma homologous subunits, each subunit comprising two transmembrane segments. Amino acid residues involved in binding of the pore blocker amiloride are located in the pre-M2 segment of beta and gamma subunits, which precedes the second putative transmembrane alpha helix (M2). A residue in the alpha subunit (alphaS589) at the NH2 terminus of M2 is critical for the molecular sieving properties of ENaC. ENaC is more permeable to Li+ than Na+ ions. The concentration of half-maximal unitary conductance is 38 mM for Na+ and 118 mM for Li+, a kinetic property that can account for the differences in Li+ and Na+ permeability. We show here that mutation of amino acid residues at homologous positions in the pre-M2 segment of alpha, beta, and gamma subunits (alphaG587, betaG529, gammaS541) decreases the Li+/Na+ selectivity by changing the apparent channel affinity for Li+ and Na+. Fitting single-channel data of the Li+ permeation to a discrete-state model including three barriers and two binding sites revealed that these mutations increased the energy needed for the translocation of Li+ from an outer ion binding site through the selectivity filter. Mutation of betaG529 to Ser, Cys, or Asp made ENaC partially permeable to K+ and larger ions, similar to the previously reported alphaS589 mutations. We conclude that the residues alphaG587 to alphaS589 and homologous residues in the beta and gamma subunits form the selectivity filter, which tightly accommodates Na+ and Li+ ions and excludes larger ions like K+.
Mots-clé
Amiloride/pharmacology, Amino Acid Sequence/genetics, Animals, Binding, Competitive, Conserved Sequence/genetics, Electric Conductivity, Epithelial Sodium Channel, Female, Ions, Lithium/metabolism, Models, Biological, Mutation/physiology, Oocytes, Permeability, Rats, Sodium/metabolism, Sodium Channel Blockers, Sodium Channels/genetics, Sodium Channels/metabolism, Xenopus
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 12:45
Dernière modification de la notice
20/08/2019 16:28
Données d'usage