ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
The interface between extracellular and transmembrane domains of homomeric Cys-loop receptors governs open-channel lifetime and rate of desensitization.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Enhanced meta-analysis of acetylcholine binding protein structures reveals conformational signatures of agonism in nicotinic receptors.Protein science : a publication of the Protein Society · 2012Pooled it
- Hidden complexity of α7 nicotinic acetylcholine receptor desensitization revealed by MD simulations and Markov state modeling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Symmetry-adapted Markov state models of closing, opening, and desensitizing in α 7 nicotinic acetylcholine receptors.Nature communications · 2024Article
- Origin of acetylcholine antagonism in ELIC, a bacterial pentameric ligand-gated ion channel.Communications biology · 2022Article
- Differential interactions of resting, activated, and desensitized states of the α7 nicotinic acetylcholine receptor with lipidic modulators.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Cannabidiol as a modulator of α7 nicotinic receptors.Cellular and molecular life sciences : CMLS · 2022Article
- The nematode serotonin-gated chloride channel MOD-1: A novel target for anthelmintic therapy.The Journal of biological chemistry · 2022Article
- Recent Insight into Lipid Binding and Lipid Modulation of Pentameric Ligand-Gated Ion Channels.Biomolecules · 2022Review
- Probing the molecular basis for signal transduction through the Zinc-Activated Channel (ZAC).Biochemical pharmacology · 2021Article
- Unbalanced Regulation of α7 nAChRs by Ly6h and NACHO Contributes to Neurotoxicity in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor.Cellular and molecular life sciences : CMLS · 2021Article
- Article
- Structure, Function and Physiology of 5-Hydroxytryptamine Receptors Subtype 3.Sub-cellular biochemistry · 2021Review
- Orthosteric and Allosteric Activation of Human 5-HTBiophysical journal · 2020Article
- Nicotinic acetylcholine receptors: Conventional and unconventional ligands and signaling.Neuropharmacology · 2020Review
- A New Antagonist ofFrontiers in neuroscience · 2020Article
- Structural basis for α-bungarotoxin insensitivity of neuronal nicotinic acetylcholine receptors.Neuropharmacology · 2019Article
- α7 nicotinic acetylcholine receptor upregulation by anti-apoptotic Bcl-2 proteins.Nature communications · 2019Article
- Potentiation of a neuronal nicotinic receptor via pseudo-agonist site.Cellular and molecular life sciences : CMLS · 2019Article
- Article
16 more citing papers are in PubMed but not listed here.
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4 authors.
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Abstract
The lifetimes of activated postsynaptic receptor channels contribute to the efficiency of synaptic transmission. Here we show that structural differences within the interface dividing extracellular and transmembrane domains of homomeric alpha7 and 5-HT(3A) receptors account for the large differences in open-channel lifetime and time of desensitization onset between these contrasting members of the Cys-loop receptor superfamily. For alpha7 receptors, agonist-evoked single-channel currents appear mainly as isolated brief openings (tau(o) = 0.35 ms), whereas macroscopic currents after a step pulse of agonist desensitize rapidly (tau(d) = 0.4 ms). In contrast for 5-HT(3A) receptors, agonist-evoked single-channel currents appear as clusters of many long openings in quick succession (tau(cluster) = 1.2 s), whereas macroscopic currents desensitize slowly (tau(d) = 1.1 s). A chimeric alpha7-5HT(3A) receptor exhibits functional properties intermediate between those of the parent receptors, but the functional signatures of each parent are reconstituted after substituting the major loops within the interface of the extracellular and transmembrane domains from the corresponding parent receptor. Furthermore, these structural loops contribute to open-channel lifetime and time of desensitization onset in a nonadditive manner. The results suggest that desensitization is the major determinant of the lifetimes of activated alpha7 and 5-HT(3A) receptors and that functional differences between the two receptors arise primarily through structural differences at the interface between extracellular and transmembrane domains.
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