Accelerated Current Decay Kinetics of a Rare Human Acid-Sensing ion Channel 1a Variant That Is Used in Many Studies as Wild Type.

Détails

Ressource 1Télécharger: Vaithia-212-fnmol-12-00133.pdf (3910.67 [Ko])
Etat: Public
Version: de l'auteur
Licence: CC BY 4.0
ID Serval
serval:BIB_B5989FB7B33D
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Compte-rendu: analyse d'une oeuvre publiée.
Collection
Publications
Titre
Accelerated Current Decay Kinetics of a Rare Human Acid-Sensing ion Channel 1a Variant That Is Used in Many Studies as Wild Type.
Périodique
Frontiers in molecular neuroscience
Auteur(s)
Vaithia A., Vullo S., Peng Z., Alijevic O., Kellenberger S.
ISSN
1662-5099 (Print)
ISSN-L
1662-5099
Statut éditorial
Publié
Date de publication
2019
Peer-reviewed
Oui
Volume
12
Pages
133
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Acid-sensing ion channels (ASICs) are neuronal Na <sup>+</sup> -permeable ion channels that are activated by extracellular acidification and are involved in fear sensing, learning, neurodegeneration after ischemia, and in pain sensation. We have recently found that the human ASIC1a (hASIC1a) wild type (WT) clone which has been used by many laboratories in recombinant expression studies contains a point mutation that occurs with a very low frequency in humans. Here, we compared the function and expression of ASIC1a WT and of this rare variant, in which the highly conserved residue Gly212 is substituted by Asp. Residue 212 is located at a subunit interface that undergoes changes during channel activity. We show that the modulation of channel function by commonly used ASIC inhibitors and modulators, and the pH dependence, are the same or only slightly different between hASIC1a-G212 and -D212. hASIC1a-G212 has however a higher current amplitude per surface-expressed channel and considerably slower current decay kinetics than hASIC1a-D212, and its current decay kinetics display a higher dependency on the type of anion present in the extracellular solution. We demonstrate for a number of channel mutants previously characterized in the hASIC1a-D212 background that they have very similar effects in the hASIC1a-G212 background. Taken together, we show that the variant hASIC1a-D212 that has been used as WT in many studies is, in fact, a mutant and that the properties of hASIC1a-D212 and hASIC1a-G212 are sufficiently close that the conclusions made in previous pharmacology and structure-function studies remain valid.
Mots-clé
Molecular Biology, Cellular and Molecular Neuroscience, ASIC, kinetics, mutation, patch-clamp, variant, voltage-clamp fluorometry
Pubmed
Web of science
Open Access
Oui
Financement(s)
Fonds national suisse / Projets / 31003A_172968
Création de la notice
28/05/2019 7:38
Dernière modification de la notice
21/08/2019 6:10
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