ArticleThe Journal of pharmacology and experimental therapeutics2010
A transmembrane amino acid in the GABAA receptor β2 subunit critical for the actions of alcohols and anesthetics.
Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- GABA system as the cause and effect in early development.Neuroscience and biobehavioral reviews · 2024Review
- Circulating MicroRNA Expression Levels Associated With Internet Gaming Disorder.Frontiers in psychiatry · 2018Article
- Novel Molecule Exhibiting Selective Affinity for GABAScientific reports · 2017Article
- Tryptophan and Cysteine Mutations in M1 Helices of α1β3γ2L γ-Aminobutyric Acid Type A Receptors Indicate Distinct Intersubunit Sites for Four Intravenous Anesthetics and One Orphan Site.Anesthesiology · 2016Article
- Mapping General Anesthetic Sites in Heteromeric γ-Aminobutyric Acid Type A Receptors Reveals a Potential For Targeting Receptor Subtypes.Anesthesia and analgesia · 2016Review
- A Cysteine Substitution Probes β3H267 Interactions with Propofol and Other Potent Anesthetics in α1β3γ2L γ-Aminobutyric Acid Type A Receptors.Anesthesiology · 2016Article
- Structural Studies of GABAA Receptor Binding Sites: Which Experimental Structure Tells us What?Frontiers in molecular neuroscience · 2016Article
- GABA(A) receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites.Journal of neurochemistry · 2014Article
- Mutations at beta N265 in γ-aminobutyric acid type A receptors alter both binding affinity and efficacy of potent anesthetics.PloS one · 2014Article
- Proteomic approaches and identification of novel therapeutic targets for alcoholism.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Review
- Functional validation of virtual screening for novel agents with general anesthetic action at ligand-gated ion channels.Molecular pharmacology · 2013Article
- Ethanol inhibition of a T-type Ca²+ channel through activity of protein kinase C.Alcoholism, clinical and experimental research · 2013Article
- Allyl m-trifluoromethyldiazirine mephobarbital: an unusually potent enantioselective and photoreactive barbiturate general anesthetic.Journal of medicinal chemistry · 2012Article
- Patterned expression of ion channel genes in mouse dorsal raphe nucleus determined with the Allen Mouse Brain Atlas.Brain research · 2012Article
- The TM2 6' position of GABA(A) receptors mediates alcohol inhibition.The Journal of pharmacology and experimental therapeutics · 2012Article
- GABA(A) receptors as molecular targets of general anesthetics: identification of binding sites provides clues to allosteric modulation.Canadian journal of anaesthesia = Journal canadien d'anesthesie · 2011Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Alcohols and inhaled anesthetics enhance the function of GABA(A) receptors containing α, β, and γ subunits. Molecular analysis has focused on the role of the α subunits; however, there is evidence that the β subunits may also be important. The goal of our study was to determine whether Asn265, which is homologous to the site implicated in the α subunit (Ser270), contributes to an alcohol and volatile anesthetic binding site in the GABA(A) receptor β(2) subunit. We substituted cysteine for Asn265 and exposed the mutant to the sulfhydryl-specific reagent octyl methanethiosulfonate (OMTS). We used two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes and found that, after OMTS application, GABA-induced currents were irreversibly potentiated in mutant α(1)β(2)(N265C)γ(2S) receptors [but not α(1)β(2)(I264C)γ(2S)], presumably because of the covalent linking of octanethiol to the thiol group in the substituted cysteine. It is noteworthy that this effect was blocked when OMTS was applied in the presence of octanol. We found that potentiation by butanol, octanol, or isoflurane in the N265C mutant was nearly abolished after the application of OMTS, suggesting that an alcohol and volatile anesthetic binding site at position 265 of the β(2) subunit was irreversibly occupied by octanethiol and consequently prevented butanol or isoflurane from binding and producing their effects. OMTS did not affect modulation or direct activation by pentobarbital, but there was a partial reduction of allosteric modulation by flunitrazepam and alphaxalone in mutant α(1)β(2)(N265C)γ(2S) receptors after OMTS was applied. Our findings provide evidence that Asn265 may contribute to an alcohol and anesthetic binding site.
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