ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Unraveling the high- and low-sensitivity agonist responses of nicotinic acetylcholine receptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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90 citing papers in PubMed, 153 citations in OpenAlex.
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- Enantiospecific Positive Allosteric Modulation of α4β2 Nicotinic Receptor Subtypes.ACS chemical neuroscience · 2025Article
- Structural Determinants of Oxantel Analogs Reveal Modulatory Selectivity of α3β2 and α4β2 Neuronal Nicotinic Acetylcholine Receptors.ACS omega · 2025Article
- SR9883 is a novel small-molecule enhancer of α4β2* nicotinic acetylcholine receptor signaling that decreases intravenous nicotine self-administration in rats.Frontiers in molecular neuroscience · 2024Article
- A potential cost of evolving epibatidine resistance in poison frogs.BMC biology · 2023Article
- Stoichiometry-selective modulation of α4β2 nicotinic ACh receptors by divalent cations.British journal of pharmacology · 2022Article
- The α9α10 nicotinic acetylcholine receptor: a compelling drug target for hearing loss?Expert opinion on therapeutic targets · 2022Review
- Neurobiological Mechanisms of Nicotine Reward and Aversion.Pharmacological reviews · 2022Review
- Acute effects of the imidacloprid metabolite desnitro-imidacloprid on human nACh receptors relevant for neuronal signaling.Archives of toxicology · 2021Article
- Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons.Archives of toxicology · 2021Article
- Loss of Choline Agonism in the Inner Ear Hair Cell Nicotinic Acetylcholine Receptor Linked to the α10 Subunit.Frontiers in molecular neuroscience · 2021Article
- Delineation of molecular determinants for FR900359 inhibition of GThe Journal of biological chemistry · 2020Article
- Article
- Heterologous expression of concatenated nicotinic ACh receptors: Pros and cons of subunit concatenation and recommendations for construct designs.British journal of pharmacology · 2020Article
- A novel fast-channel myasthenia caused by mutation in β subunit of AChR reveals subunit-specific contribution of the intracellular M1-M2 linker to channel gating.Experimental neurology · 2020Article
- Cotinine and 6-Hydroxy-L-Nicotine Reverses Memory Deficits and Reduces Oxidative Stress in AβAntioxidants (Basel, Switzerland) · 2020Article
- Interactions of the α3β2 Nicotinic Acetylcholine Receptor Interfaces with α-Conotoxin LsIA and its Carboxylated C-terminus Analogue: Molecular Dynamics Simulations.Marine drugs · 2020Article
- Progress in nicotinic receptor structural biology.Neuropharmacology · 2020Review
- The α5 Nicotinic Acetylcholine Receptor Subunit Differentially Modulates α4β2Frontiers in synaptic neuroscience · 2020Review
30 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neuronal α4β2 nicotinic acetylcholine receptors exist as two distinct subtypes, (α4)(2)(β2)(3) and (α4)(3)(β2)(2), and biphasic responses to acetylcholine and other agonists have been ascribed previously to coexistence of these two receptor subtypes. We offer a novel and radical explanation for the observation of two distinct agonist sensitivities. Using different expression ratios of mammalian α4 and β2 subunits and concatenated constructs, we demonstrate that a biphasic response is an intrinsic functional property of the (α4)(3)(β2)(2) receptor. In addition to two high-sensitivity sites at α4β2 interfaces, the (α4)(3)(β2)(2) receptor contains a third low-sensitivity agonist binding site in the α4α4 interface. Occupation of this site is required for full activation and is responsible for the widened dynamic response range of this receptor subtype. By site-directed mutagenesis, we show that three residues, which differ between the α4β2 and α4α4 sites, control agonist sensitivity. The results presented here provide a basic insight into the function of pentameric ligand-gated ion channels, which enables modulation of the receptors with hitherto unseen precision; it becomes possible to rationally design therapeutics targeting subpopulations of specific receptor subtypes.
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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.