Hydroxylated residues influence desensitization behaviour of recombinant alpha3 glycine receptor channels.

Détails

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Etat: Supprimée
Version: de l'auteur⸱e
ID Serval
serval:BIB_1DD42597E823
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Hydroxylated residues influence desensitization behaviour of recombinant alpha3 glycine receptor channels.
Périodique
Journal of Neurochemistry
Auteur⸱e⸱s
Breitinger H.G., Villmann C., Rennert J., Ballhausen D., Becker C.M.
ISSN
0022-3042 (Print)
ISSN-L
0022-3042
Statut éditorial
Publié
Date de publication
2002
Peer-reviewed
Oui
Volume
83
Numéro
1
Pages
30-36
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
The human glycine receptor subunit alpha3 exists in two splice variants (alpha3K/L), with alpha3L bearing an additional segment of 15 amino acids within the cytoplasmic TM3-4 loop. Homomeric alpha3K glycine receptors show faster desensitization than alpha3L receptors. Ion channel properties were compared of alpha3L, alpha3K, and of the triple mutant alpha3LDeltaOH = alpha3L(T358A/Y367F/S370A), where hydroxyl functions of the spliced insert had been removed by site-directed mutagenesis. Upon recombinant expression in HEK 293 cells, patch-clamp recording experiments revealed that removal of hydroxyl functions primarily affected receptor desensitization. The fraction of non-desensitizing current was 68 +/- 13% for alpha3L, 21 +/- 13% for alpha3K, and 48 +/- 16% for alpha3LDeltaOH. Desensitization time constants at saturating glycine concentration were 8.4 +/- 2.8 s, 1.9 +/- 2.3 s, and 2.8 +/- 0.4 s, for alpha3L, alpha3K, and the triple mutant alpha3LDeltaOH, respectively. In contrast, single-channel and whole-cell properties were similar for all three constructs. Thus, ion channel activation, desensitization, and conductance properties are independently controlled by distinct structural elements. Hydroxyl functions within the M3-4 loop of the glycine receptor alpha3 subunit are crucial, but not exclusive, determinants of receptor desensitization.
Mots-clé
Alternative Splicing, Biological Transport/physiology, Blotting, Western, Cell Line, Dose-Response Relationship, Drug, Electrophysiology, Glycine/pharmacokinetics, Humans, Hydroxylation, Kidney/cytology, Kidney/metabolism, Mutagenesis, Site-Directed, Patch-Clamp Techniques, Protein Subunits, Receptors, Glycine/genetics, Receptors, Glycine/metabolism, Structure-Activity Relationship, Transfection
Pubmed
Web of science
Création de la notice
29/03/2010 13:21
Dernière modification de la notice
20/08/2019 13:54
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