ArticleJournal of neurochemistry2014
GABA(A) receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites.
Article in Journal of neurochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Substituted Cysteine Modification and Protection with n-Alkyl-MTS Reagents Quantifies Steric Changes Induced by a Mutation in Anesthetic Binding Sites on GABA Type A Receptors.Molecular pharmacology · 2023Article
- Mobility of Lower MA-Helices for Ion Conduction through Lateral Portals in 5-HTBiophysical journal · 2020Article
- Molecular basis for potentiation of Cx36 gap junction channel conductance byBioscience reports · 2018Article
- Alphaxalone Binds in Inner Transmembrane β+-α- Interfaces of α1β3γ2 γ-Aminobutyric Acid Type A Receptors.Anesthesiology · 2018Article
- Combining Mutations and Electrophysiology to Map Anesthetic Sites on Ligand-Gated Ion Channels.Methods in enzymology · 2018Review
- Novel Molecule Exhibiting Selective Affinity for GABAScientific reports · 2017Article
- Titrating Tipsy Targets: The Neurobiology of Low-Dose Alcohol.Trends in pharmacological sciences · 2017Review
- 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
- Alcohol modulation of BK channel gating depends on β subunit composition.The Journal of general physiology · 2016Article
- Inter- and Intra-Subunit Butanol/Isoflurane Sites of Action in the Human Glycine Receptor.Frontiers in molecular neuroscience · 2016Article
- Early life stress is a risk factor for excessive alcohol drinking and impulsivity in adults and is mediated via a CRF/GABA(A) mechanism.Stress (Amsterdam, Netherlands) · 2016Article
- Cysteine substitution of transmembrane domain amino acids alters the ethanol inhibition of GluN1/GluN2A N-methyl-D-aspartate receptors.The Journal of pharmacology and experimental therapeutics · 2015Article
- The molecular pharmacology of volatile anesthetics.International anesthesiology clinics · 2015Review
- Direct gating of ATP-activated ion channels (P2X2 receptors) by lipophilic attachment at the outer end of the second transmembrane domain.The Journal of biological chemistry · 2014Article
- Mutations at beta N265 in γ-aminobutyric acid type A receptors alter both binding affinity and efficacy of potent anesthetics.PloS one · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Alcohols and inhaled anesthetics modulate GABA(A) receptor (GABA(A)R) function via putative binding sites within the transmembrane regions. The relative position of the amino acids lining these sites could be either inter- or intra-subunit. We introduced cysteines in relevant TM locations and tested the proximity of cysteine pairs using oxidizing and reducing agents to induce or break disulfide bridges between cysteines, and thus change GABA-mediated currents in wild-type and mutant α1β2γ2 GABA(A)Rs expressed in Xenopus laevis oocytes. We tested for: (i) inter-subunit cross-linking: a cysteine located in α1TM1 [either α1(Q229C) or α1(L232C)] was paired with a cysteine in different positions of β2TM2 and TM3; (ii) intra-subunit cross-linking: a cysteine located either in β2TM1 [β2(T225C)] or in TM2 [β2(N265C)] was paired with a cysteine in different locations along β2TM3. Three inter-subunit cysteine pairs and four intra-subunits cross-linked. In three intra-subunit cysteine combinations, the alcohol effect was reduced by oxidizing agents, suggesting intra-subunit alcohol binding. We conclude that the structure of the alcohol binding site changes during activation and that potentiation or inhibition by binding at inter- or intra-subunit sites is determined by the specific receptor and ligand.
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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.