ArticleProceedings of the National Academy of Sciences of the United States of America2012
Depolarization induces a conformational change in the binding site region of the M2 muscarinic receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
24 citing papers in PubMed, 37 citations in OpenAlex.
- Action Potential Firing Patterns Regulate Dopamine Release via Voltage-Sensitive Dopamine D2 Autoreceptors in Mouse Striatum In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Different fluorescent labels report distinct components of spHCN channel voltage sensor movement.The Journal of general physiology · 2024Article
- Voltage Sensors Embedded in G Protein-Coupled Receptors.International journal of molecular sciences · 2024Review
- Are Voltage Sensors Really Embedded in Muscarinic Receptors?International journal of molecular sciences · 2023Article
- Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands.International journal of molecular sciences · 2023Review
- G Protein-Coupled Receptors Regulated by Membrane Potential.International journal of molecular sciences · 2022Review
- The activity of the serotonergic 5-HTThe Journal of biological chemistry · 2022Article
- Differential voltage-dependent modulation of the ACh-gated K+ current by adenosine and acetylcholine.PloS one · 2022Article
- Voltage dependence of the cannabinoid CB1 receptor.Frontiers in pharmacology · 2022Article
- Article
- Voltage modulates the effect of μ-receptor activation in a ligand-dependent manner.British journal of pharmacology · 2020Article
- Sodium ions allosterically modulate the M2 muscarinic receptor.Scientific reports · 2020Article
- Article
- Regulation of heterologously expressed 5-HTBritish journal of pharmacology · 2019Article
- Site-Directed Fluorescence Approaches for Dynamic Structural Biology of Membrane Peptides and Proteins.Frontiers in molecular biosciences · 2019Review
- Gating currents.The Journal of general physiology · 2018Review
- Structural determinants at the M2 muscarinic receptor modulate the RGS4-GIRK response to pilocarpine by impairment of the receptor voltage sensitivity.Scientific reports · 2017Article
- A Novel Voltage Sensor in the Orthosteric Binding Site of the M2 Muscarinic Receptor.Biophysical journal · 2016Article
- Structural Mechanisms of Voltage Sensing in G Protein-Coupled Receptors.Structure (London, England : 1993) · 2016Article
- Distance mapping in proteins using fluorescence spectroscopy: tyrosine, like tryptophan, quenches bimane fluorescence in a distance-dependent manner.Biochemistry · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
G protein-coupled receptors play a central role in signal transduction and were only known to be activated by agonists. Recently it has been shown that membrane potential also affects the activity of G protein-coupled receptors. For the M(2) muscarinic receptor, it was further shown that depolarization induces charge movement. A tight correlation was found between the voltage-dependence of the charge movement and the voltage-dependence of the agonist binding. Here we examine whether depolarization-induced charge movement causes a conformational change in the M(2) receptor that may be responsible for the voltage-dependence of agonist binding. Using site-directed fluorescence labeling we show a voltage-dependent fluorescence signal, reflecting a conformational change, which correlates with the voltage-dependent charge movement. We further show that selected mutations in the orthosteric site abolish the fluorescence signal and concomitantly, the voltage-dependence of the agonist binding. Surprisingly, mutations in the allosteric site also abolished the voltage-dependence of agonist binding but did not reduce the fluorescence signal. Finally, we show that treatments, which reduced the charge movement or hindered the coupling between the charge movement and the voltage-dependent binding, also reduced the fluorescence signal. Our results demonstrate that depolarization-induced conformational changes in the orthosteric binding site underlie the voltage-dependence of agonist binding. Our results are also unique in suggesting that the allosteric site is also involved in controlling the voltage-dependent agonist binding.
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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.