ArticleNature2009
Detection and trapping of intermediate states priming nicotinic receptor channel opening.
Article in Nature, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
135 citing papers in PubMed.
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- Celebrating 50 Years of Single-Channel Recording with the Patch Clamp.The Journal of membrane biology · 2025Review
- Disentangling the mechanistic role of loop-C capping in Cys-loop receptor activation.Nature communications · 2025Article
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- Divergent mechanisms of steroid inhibition in the human ρ1 GABANature communications · 2024Article
- Dynamics of receptor activation by agonists.Biophysical journal · 2024Review
- The affinity-efficacy problem: an essential part of pharmacology education.Royal Society open science · 2024Review
- Mapping the molecular motions of 5-HTeLife · 2024Article
- Structural basis for partial agonism in 5-HTNature structural & molecular biology · 2024Article
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- Mechanistic basis of ligand efficacy in the calcium-activated chloride channel TMEM16A.The EMBO journal · 2023Article
- Impaired gating of γ- and ε-AChR respectively causes Escobar syndrome and fast-channel myasthenia.Annals of clinical and translational neurology · 2023Article
- Derepression may masquerade as activation in ligand-gated ion channels.Nature communications · 2023Article
- A Functional Interaction Between Y674-R685 Region of the SARS-CoV-2 Spike Protein and the Human α7 Nicotinic Receptor.Molecular neurobiology · 2022Article
- Ancestral acetylcholine receptor β-subunit forms homopentamers that prime before opening spontaneously.eLife · 2022Article
- Stoichiometry-selective modulation of α4β2 nicotinic ACh receptors by divalent cations.British journal of pharmacology · 2022Article
- Article
- Bibliometric analysis of nicotinic acetylcholine receptors channel research (2000-2020).Channels (Austin, Tex.) · 2021Review
- Article
- Dynamic closed states of a ligand-gated ion channel captured by cryo-EM and simulations.Life science alliance · 2021Article
75 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
In the course of synaptic transmission in the brain and periphery, acetylcholine receptors (AChRs) rapidly transduce a chemical signal into an electrical impulse. The speed of transduction is facilitated by rapid ACh association and dissociation, suggesting a binding site relatively non-selective for small cations. Selective transduction has been thought to originate from the ability of ACh, over that of other organic cations, to trigger the subsequent channel-opening step. However, transitions to and from the open state were shown to be similar for agonists with widely different efficacies. By studying mutant AChRs, we show here that the ultimate closed-to-open transition is agonist-independent and preceded by two primed closed states; the first primed state elicits brief openings, whereas the second elicits long-lived openings. Long-lived openings and the associated primed state are detected in the absence and presence of an agonist, and exhibit the same kinetic signatures under both conditions. By covalently locking the agonist-binding sites in the bound conformation, we find that each site initiates a priming step. Thus, a change in binding-site conformation primes the AChR for channel opening in a process that enables selective activation by ACh while maximizing the speed and efficiency of the biological response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.