ArticleThe Journal of physiology2009
Agonist and blocking actions of choline and tetramethylammonium on human muscle acetylcholine receptors.
Article in The Journal of physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
- Ancestral acetylcholine receptor β-subunit forms homopentamers that prime before opening spontaneously.eLife · 2022Article
- Interplay between Gating and Block of Ligand-Gated Ion Channels.Brain sciences · 2020Review
- The dual-gate model for pentameric ligand-gated ion channels activation and desensitization.The Journal of physiology · 2018Review
- Full and partial agonists evoke distinct structural changes in opening the muscle acetylcholine receptor channel.The Journal of general physiology · 2018Article
- Molecular recognition at cholinergic synapses: acetylcholine versus choline.The Journal of physiology · 2017Article
- Muscle-Type Nicotinic Receptor Modulation by 2,6-Dimethylaniline, a Molecule Resembling the Hydrophobic Moiety of Lidocaine.Frontiers in molecular neuroscience · 2016Article
- Mechanism of activation of the prokaryotic channel ELIC by propylamine: a single-channel study.The Journal of general physiology · 2015Article
- The kinetic properties of the α3 rat glycine receptor make it suitable for mediating fast synaptic inhibition.The Journal of physiology · 2013Article
- Energy for wild-type acetylcholine receptor channel gating from different choline derivatives.Biophysical journal · 2013Article
- Nicotinic receptor transduction zone: invariant arginine couples to multiple electron-rich residues.Biophysical journal · 2013Article
- Energetic contributions to channel gating of residues in the muscle nicotinic receptor β1 subunit.PloS one · 2013Article
- Perspectives on: conformational coupling in ion channels: allosteric coupling in ligand-gated ion channels.The Journal of general physiology · 2012Article
- End-plate acetylcholine receptor: structure, mechanism, pharmacology, and disease.Physiological reviews · 2012Review
- The α1K276E startle disease mutation reveals multiple intermediate states in the gating of glycine receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- The long activations of α2 glycine channels can be described by a mechanism with reaction intermediates ("flip").The Journal of general physiology · 2011Article
- Probing pore constriction in a ligand-gated ion channel by trapping a metal ion in the pore upon agonist dissociation.The Journal of biological chemistry · 2010Article
- The activation mechanism of alpha1beta2gamma2S and alpha3beta3gamma2S GABAA receptors.The Journal of general physiology · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Choline has been used widely as an agonist for the investigation of gain-of-function mutants of the nicotinic acetylcholine receptor. It is useful because it behaves like a partial agonist. The efficacy of choline is difficult to measure because choline blocks the channel at concentrations about four times lower than those that activate it. We have fitted activation mechanisms to single-channel activity elicited from HEK-expressed human recombinant muscle nicotinic receptors by choline and by tetramethylammonium (TMA). Channel block by the agonist was incorporated into the mechanisms that were fitted, and block was found not to be selective for the open state. The results also suggest that channel block is very fast and that the channel can shut almost as fast as normal when the blocker was bound. Single-channel data are compatible with a mechanism in which choline is actually a full agonist, its maximum response being limited only by channel block. However, they are also compatible with a mechanism incorporating a pre-opening conformation change ('flip') in which choline is a genuine partial agonist. The latter explanation is favoured by concentration jump experiments, and by the fact that only this mechanism fits the TMA data. We propose that choline, like TMA, is a partial agonist because it is very ineffective (approximately 600-fold less than acetylcholine) at eliciting the initial, pre-opening conformation change. Once flipping has occurred, all agonists, even choline, open the channel with similar efficiency.
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What OpenQuestion holds
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.