ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Enhanced tonic inhibition influences the hypnotic and amnestic actions of the intravenous anesthetics etomidate and propofol.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Propofol regulates arousal by enhancing inhibitory synaptic transmission of noradrenergic neurons in the locus coeruleus of adult male mice.Scientific reports · 2025Article
- Preventing Phosphorylation of the GABAFrontiers in molecular neuroscience · 2022Article
- Metabotropic, but not allosteric, effects of neurosteroids on GABAergic inhibition depend on the phosphorylation of GABAThe Journal of biological chemistry · 2019Article
- Identification of a Core Amino Acid Motif within the α Subunit of GABACell reports · 2019Article
- Etomidate Effects on Desensitization and Deactivation ofThe Journal of pharmacology and experimental therapeutics · 2019Article
- Neuroactive Steroids Reverse Tonic Inhibitory Deficits in Fragile X Syndrome Mouse Model.Frontiers in molecular neuroscience · 2019Article
- GABA type a receptor trafficking and the architecture of synaptic inhibition.Developmental neurobiology · 2018Review
- Zebrafish: A Pharmacogenetic Model for Anesthesia.Methods in enzymology · 2018Article
- Endogenous and synthetic neuroactive steroids evoke sustained increases in the efficacy of GABAergic inhibition via a protein kinase C-dependent mechanism.Neuropharmacology · 2017Article
- Clarithromycin increases neuronal excitability in CA3 pyramidal neurons through a reduction in GABAergic signaling.Journal of neurophysiology · 2017Article
- The Influence of Regional Distribution and Pharmacologic Specificity of GABAFrontiers in systems neuroscience · 2017Review
- General Anesthetic Binding Sites in Human α4β3δ γ-Aminobutyric Acid Type A Receptors (GABAARs).The Journal of biological chemistry · 2016Article
- Neonatal Propofol and Etomidate Exposure Enhance Inhibitory Synaptic Transmission in Hippocampal Cornus Ammonis 1 Pyramidal Neurons.Chinese medical journal · 2016Article
- Regulating the Efficacy of Inhibition Through Trafficking of γ-Aminobutyric Acid Type A Receptors.Anesthesia and analgesia · 2016Review
- Genetic Deletion of the Clathrin Adaptor GGA3 Reduces Anxiety and Alters GABAergic Transmission.PloS one · 2016Article
- Compromising the phosphodependent regulation of the GABAAR β3 subunit reproduces the core phenotypes of autism spectrum disorders.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Propofol inhibits SIRT2 deacetylase through a conformation-specific, allosteric site.The Journal of biological chemistry · 2015Article
- Study of GABAergic extra-synaptic tonic inhibition in single neurons and neural populations by traversing neural scales: application to propofol-induced anaesthesia.Journal of computational neuroscience · 2014Article
- Thalamic δ-subunit containing GABAA receptors promote electrocortical signatures of deep non-REM sleep but do not mediate the effects of etomidate at the thalamus in vivo.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Phosphorylation of GABAA receptors influences receptor trafficking and neurosteroid actions.Psychopharmacology · 2014Review
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Authors and funding
9 authors.
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Abstract
Intravenous anesthetics exert a component of their actions via potentiating inhibitory neurotransmission mediated by γ-aminobutyric type-A receptors (GABAARs). Phasic and tonic inhibition is mediated by distinct populations of GABAARs, with the majority of phasic inhibition by subtypes composed of α1-3βγ2 subunits, whereas tonic inhibition is dependent on subtypes assembled from α4-6βδ subunits. To explore the contribution that these distinct forms of inhibition play in mediating intravenous anesthesia, we have used mice in which tyrosine residues 365/7 within the γ2 subunit are mutated to phenyalanines (Y365/7F). Here we demonstrate that this mutation leads to increased accumulation of the α4 subunit containing GABAARs in the thalamus and dentate gyrus of female Y365/7F but not male Y365/7F mice. Y365/7F mice exhibited a gender-specific enhancement of tonic inhibition in the dentate gyrus that was more sensitive to modulation by the anesthetic etomidate, together with a deficit in long-term potentiation. Consistent with this, female Y365/7F, but not male Y365/7F, mice exhibited a dramatic increase in the duration of etomidate- and propofol-mediated hypnosis. Moreover, the amnestic actions of etomidate were selectively potentiated in female Y365/7F mice. Collectively, these observations suggest that potentiation of tonic inhibition mediated by α4 subunit containing GABAARs contributes to the hypnotic and amnestic actions of the intravenous anesthetics, etomidate and propofol.
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