ArticleAnesthesiology2011
A Single phenylalanine residue in the main intracellular loop of α1 γ-aminobutyric acid type A and glycine receptors influences their sensitivity to propofol.
Article in Anesthesiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Mechanism of human α3β GlyR regulation by intracellular M3/M4 loop phosphorylation and 2,6-di-tert-butylphenol interaction.Nature communications · 2025Article
- Allosteric modulation and direct activation of glycine receptors by a tricyclic sulfonamide.Scientific reports · 2025Article
- Schisandrin B, a dual positive allosteric modulator of GABAActa pharmacologica Sinica · 2024Article
- Modulation of GABAFrontiers in molecular neuroscience · 2022Article
- Glycine Receptors in Spinal Nociceptive Control-An Update.Biomolecules · 2021Review
- Modulatory Actions of the Glycine Receptor β Subunit on the Positive Allosteric Modulation of Ethanol in α2 Containing Receptors.Frontiers in molecular neuroscience · 2021Article
- Modulation of glycine receptor single-channel conductance by intracellular phosphorylation.Scientific reports · 2020Article
- The Effects of General Anesthetics on Synaptic Transmission.Current neuropharmacology · 2020Review
- The effects of insecticides on two splice variants of the glutamate-gated chloride channel receptor of the major malaria vector, Anopheles gambiae.British journal of pharmacology · 2020Article
- Triple arginines as molecular determinants for pentameric assembly of the intracellular domain of 5-HTThe Journal of general physiology · 2019Article
- Identifying Drugs that Bind Selectively to Intersubunit General Anesthetic Sites in theMolecular pharmacology · 2019Article
- Identification of binding sites contributing to volatile anesthetic effects on GABA type A receptors.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Glycine receptors and glycine transporters: targets for novel analgesics?Cellular and molecular life sciences : CMLS · 2018Review
- Presence of Inhibitory Glycinergic Transmission in Medium Spiny Neurons in the Nucleus Accumbens.Frontiers in molecular neuroscience · 2018Article
- Curcumol allosterically modulates GABA(A) receptors in a manner distinct from benzodiazepines.Scientific reports · 2017Article
- Structure and Pharmacologic Modulation of Inhibitory Glycine Receptors.Molecular pharmacology · 2016Review
- Phosphorylation state-dependent modulation of spinal glycine receptors alleviates inflammatory pain.The Journal of clinical investigation · 2016Article
- Direct interaction of the resistance to inhibitors of cholinesterase type 3 protein with the serotonin receptor type 3A intracellular domain.Journal of neurochemistry · 2016Article
- Structural Studies of GABAA Receptor Binding Sites: Which Experimental Structure Tells us What?Frontiers in molecular neuroscience · 2016Article
- Ethanol effects on glycinergic transmission: From molecular pharmacology to behavior responses.Pharmacological research · 2015Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundThe intravenous anesthetic propofol acts as a positive allosteric modulator of glycine (GlyRs) and γ-aminobutyric acid type A (GABAARs) receptors. Although the role of transmembrane residues is recognized, little is known about the involvement of other regions in the modulatory effects of propofol. Therefore, the influence of the large intracellular loop in propofol sensitivity of both receptors was explored.
methodsThe large intracellular loop of α1 GlyRs and α1β2 GABAARs was screened using alanine replacement. Sensitivity to propofol was studied using patch-clamp recording in HEK293 cells transiently transfected with wild type or mutant receptors.
resultsAlanine mutation of a conserved phenylalanine residue within the α1 large intracellular loop significantly reduced propofol enhancement in both GlyRs (360 ± 30 vs. 75 ± 10%, mean ± SEM) and GABAARs (361 ± 49% vs. 80 ± 23%). Remarkably, propofol-hyposensitive mutant receptors retained their sensitivity to other allosteric modulators such as alcohols, etomidate, trichloroethanol, and isoflurane. At the single-channel level, the ability of propofol to increase open probability was significantly reduced in both α1 GlyR (189 ± 36 vs. 22 ± 13%) and α1β2 GABAAR (279 ± 29 vs. 29 ± 11%) mutant receptors.
conclusionIn this study, it is demonstrated that the large intracellular loop of both GlyR and GABAAR has a conserved single phenylalanine residue (F380 and F385, respectively) that influences its sensitivity to propofol. Results suggest a new role of the large intracellular loop in the allosteric modulation of two members of the Cys-loop superfamily. Thus, these data provide new insights into the molecular framework behind the modulation of inhibitory ion channels by propofol.
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