Derepression may masquerade as activation in ligand-gated ion channels.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 04 2023
05 04 2023
Historique:
received:
26
08
2022
accepted:
16
02
2023
medline:
7
4
2023
entrez:
5
4
2023
pubmed:
6
4
2023
Statut:
epublish
Résumé
Agonists are ligands that bind to receptors and activate them. In the case of ligand-gated ion channels, such as the muscle-type nicotinic acetylcholine receptor, mechanisms of agonist activation have been studied for decades. Taking advantage of a reconstructed ancestral muscle-type β-subunit that forms spontaneously activating homopentamers, here we show that incorporation of human muscle-type α-subunits appears to repress spontaneous activity, and furthermore that the presence of agonist relieves this apparent α-subunit-dependent repression. Our results demonstrate that rather than provoking channel activation/opening, agonists may instead 'inhibit the inhibition' of intrinsic spontaneous activity. Thus, agonist activation may be the apparent manifestation of agonist-induced derepression. These results provide insight into intermediate states that precede channel opening and have implications for the interpretation of agonism in ligand-gated ion channels.
Identifiants
pubmed: 37019877
doi: 10.1038/s41467-023-36770-z
pii: 10.1038/s41467-023-36770-z
pmc: PMC10076327
doi:
Substances chimiques
Ligand-Gated Ion Channels
0
Receptors, Nicotinic
0
Ligands
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1907Informations de copyright
© 2023. The Author(s).
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