ArticleThe Journal of physiology2011
Conformational changes in the M2 muscarinic receptor induced by membrane voltage and agonist binding.
Article in The Journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- Charge Movements and Conformational Changes: Biophysical Properties and Physiology of Voltage-Dependent GPCRs.Biomolecules · 2024Review
- The Role of KCells · 2024Review
- Voltage Sensors Embedded in G Protein-Coupled Receptors.International journal of molecular sciences · 2024Review
- Article
- 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
- Insights into intercellular receptor-ligand binding kinetics in cell communication.Frontiers in bioengineering and biotechnology · 2022Review
- 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
- G protein-coupled receptors of class A harness the energy of membrane potential to increase their sensitivity and selectivity.Biochimica et biophysica acta. Biomembranes · 2019Article
- Harnessing Ion-Binding Sites for GPCR Pharmacology.Pharmacological reviews · 2019Review
- Article
- The voltage-sensitive cardiac MPflugers Archiv : European journal of physiology · 2018Article
- Modeling effects of voltage dependent properties of the cardiac muscarinic receptor on human sinus node function.PLoS computational biology · 2018Article
- Determining the molecular basis of voltage sensitivity in membrane proteins.The Journal of general physiology · 2018Article
- Intracellular Transfer of NaStructure (London, England : 1993) · 2018Article
- Structural determinants at the M2 muscarinic receptor modulate the RGS4-GIRK response to pilocarpine by impairment of the receptor voltage sensitivity.Scientific reports · 2017Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability to sense transmembrane voltage is a central feature of many membrane proteins, most notably voltage-gated ion channels. Gating current measurements provide valuable information on protein conformational changes induced by voltage. The recent observation that muscarinic G-protein-coupled receptors (GPCRs) generate gating currents confirms their intrinsic capacity to sense the membrane electrical field. Here, we studied the effect of voltage on agonist activation of M2 muscarinic receptors (M2R) in atrial myocytes and how agonist binding alters M2R gating currents. Membrane depolarization decreased the potency of acetylcholine (ACh), but increased the potency and efficacy of pilocarpine (Pilo), as measured by ACh-activated K+ current, I(KACh). Voltage-induced conformational changes in M2R were modified in a ligand-selective manner: ACh reduced gating charge displacement while Pilo increased the amount of charge displaced. Thus, these ligands manifest opposite voltage-dependent I(KACh) modulation and exert opposite effects on M2R gating charge displacement. Finally, mutations in the putative ligand binding site perturbed the movement of the M2R voltage sensor. Our data suggest that changes in voltage induce conformational changes in the ligand binding site that alter the agonist–receptor interaction in a ligand-dependent manner. Voltage-dependent GPCR modulation has important implications for cellular signalling in excitable tissues. Gating current measurement allows for the tracking of subtle conformational changes in the receptor that accompany agonist binding and changes in membrane voltage.
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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.