Proton and non-proton activation of ASIC channels.
Details
Download: journal.pone.0175293.pdf (5023.66 [Ko])
State: Public
Version: Final published version
State: Public
Version: Final published version
Serval ID
serval:BIB_CE061D1AF63A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Proton and non-proton activation of ASIC channels.
Journal
PloS one
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
12
Number
4
Pages
e0175293
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
The Acid-Sensing Ion Channels (ASIC) exhibit a fast desensitizing current when activated by pH values below 7.0. By contrast, non-proton ligands are able to trigger sustained ASIC currents at physiological pHs. To analyze the functional basis of the ASIC desensitizing and sustained currents, we have used ASIC1a and ASIC2a mutants with a cysteine in the pore vestibule for covalent binding of different sulfhydryl reagents. We found that ASIC1a and ASIC2a exhibit two distinct currents, a proton-induced desensitizing current and a sustained current triggered by sulfhydryl reagents. These currents differ in their pH dependency, their sensitivity to the sulfhydryl reagents, their ionic selectivity and their relative magnitude. We propose a model for ASIC1 and ASIC2 activity where the channels can function in two distinct modes, a desensitizing mode and a sustained mode depending on the activating ligands. The pore vestibule of the channel represents a functional site for binding non-proton ligands to activate ASIC1 and ASIC2 at neutral pH and to prevent channel desensitization.
Pubmed
Web of science
Open Access
Yes
Create date
25/04/2017 18:16
Last modification date
17/09/2020 9:17