ReviewCurrent neuropharmacology2016
Multiple Non-Equivalent Interfaces Mediate Direct Activation of GABAA Receptors by Propofol.
Review in Current neuropharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
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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.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Median effective dose and 95% effective dose of oliceridine combined with ciprofol for painless gastroscopy: a dose-finding study based on Dixon's up-and-down method.Frontiers in pharmacology · 2026Article
- Neural Circuit Mechanisms of General Anaesthesia Induction: Current Advances and Future Directions.Current neuropharmacology · 2026Review
- Direct measurements of neurosteroid binding to specific sites on GABABritish journal of pharmacology · 2024Article
- A bupropion modulatory site in the Gloeobacter violaceus ligand-gated ion channel.Biophysical journal · 2024Article
- Potentiation of the GABABiophysical journal · 2024Article
- Tabernanthalog and ibogainalog inhibit the α7 and α9α10 nicotinic acetylcholine receptors via different mechanisms and with higher potency than the GABABiochemical pharmacology · 2024Article
- Chemical, Pharmacological, and Structural Characterization of Novel Acrylamide-Derived Modulators of the GABAMolecular pharmacology · 2023Article
- Mutational Analysis of Anesthetic Binding Sites and Their Effects on GABABiomolecules · 2023Article
- Modulation of the mammalian GABABritish journal of pharmacology · 2022Article
- Activation of the Rat α1β2ε GABABiomolecules · 2022Article
- Perspective on the Relationship between GABAA Receptor Activity and the Apparent Potency of an Inhibitor.Current neuropharmacology · 2022Article
- Enhancement of Muscimol Binding and Gating by Allosteric Modulators of the GABAMolecular pharmacology · 2020Article
- Analysis of Modulation of theMolecular pharmacology · 2020Article
- Site-specific effects of neurosteroids on GABAeLife · 2020Article
- Article
- The Effects of General Anesthetics on Synaptic Transmission.Current neuropharmacology · 2020Review
- Steady-state activation of the high-affinity isoform of the α4β2δ GABAScientific reports · 2019Article
- Steady-state activation and modulation of the synaptic-type α1β2γ2L GABAPhysiological reports · 2019Article
- Steady-State Activation and Modulation of the ConcatemericMolecular pharmacology · 2019Article
- Multiple functional neurosteroid binding sites on GABAA receptors.PLoS biology · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPropofol is a sedative agent that at clinical concentrations acts by allosterically activating or potentiating the γ-aminobutyric acid type A (GABAA) receptor. Mutational, modeling, and photolabeling studies with propofol and its analogues have identified potential interaction sites in the transmembrane domain of the receptor. At the "+" of the β subunit, in the β-α interface, meta-azipropofol labels the M286 residue in the third transmembrane domain. Substitution of this residue with tryptophan results in loss of potentiation by propofol. At the "-" side of the β subunit, in the α-β interface (or β-β interface, in the case of homomeric β receptors), ortho-propofol diazirine labels the H267 residue in the second transmembrane domain. Structural modeling indicates that the β(H267) residue lines a cavity that docks propofol with favorable interaction energy.
methodWe used two-electrode voltage clamp to determine the functional effects of mutations to the "+" and "-" sides of the β subunit on activation of the α1β3 GABAA receptor by propofol.
resultsWe found that while the individual mutations had a small effect, the combination of the M286W mutation with tryptophan mutations of selected residues at the α-β interface leads to strong reduction in gating efficacy for propofol.
conclusionWe conclude that α1β3 GABAA receptors can be activated by propofol interactions with the β-β, α-β, and β-α interfaces, where distinct, non-equivalent regions control channel gating. Any interface can mediate activation, hence substitutions at all interfaces are required for loss of activation by propofol.
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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.