ArticleNeuropharmacology2009
Etomidate, propofol and the neurosteroid THDOC increase the GABA efficacy of recombinant alpha4beta3delta and alpha4beta3 GABA A receptors expressed in HEK cells.
Article in Neuropharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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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Who cites it
37 citing papers in PubMed, 53 citations in OpenAlex.
- The human GABAbioRxiv : the preprint server for biology · 2026Article
- The human GABAmicroPublication biology · 2026Article
- Guanidino compounds with native GABA(A) δ receptor selectivity: a tale of homeostatic compensation in δ-KO mice.BMC neuroscience · 2025Article
- Neurosteroids: mechanistic considerations and clinical prospects.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- GABAFrontiers in pharmacology · 2023Article
- Steady-state activation of the high-affinity isoform of the α4β2δ GABAScientific reports · 2019Article
- 2-(4-methyl-thiazol-5-yl) ethyl nitrate maleate-potentiated GABACNS neuroscience & therapeutics · 2018Article
- Comparison of αβδ and αβγ GABAPharmacological research · 2018Review
- Modulation of Tonic GABA Currents by Anion Channel and Connexin Hemichannel Antagonists.Neurochemical research · 2017Article
- Methylene blue inhibits GABANeuropharmacology · 2017Article
- Assessment of subunit-dependent direct gating and allosteric modulatory effects of carisoprodol at GABA(A) receptors.Neuropharmacology · 2015Article
- Etomidate uniquely modulates the desensitization of recombinant α1β3δ GABA(A) receptors.Neuroscience · 2015Article
- A Multifaceted GABAA Receptor Modulator: Functional Properties and Mechanism of Action of the Sedative-Hypnotic and Recreational Drug Methaqualone (Quaalude).Molecular pharmacology · 2015Article
- In vitro gamma oscillations following partial and complete ablation of δ subunit-containing GABAA receptors from parvalbumin interneurons.Neuropharmacology · 2015Article
- The general anesthetic propofol induces ictal-like seizure activity in hippocampal mouse brain slices.SpringerPlus · 2015Article
- Probing α4βδ GABAA receptor heterogeneity: differential regional effects of a functionally selective α4β1δ/α4β3δ receptor agonist on tonic and phasic inhibition in rat brain.The Journal of neuroscience : the official journal of the Society for 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
- GABAA-R α4 subunits are required for the low dose locomotor stimulatory effect of alphaxalone, but not for several other behavioral responses to alphaxalone, etomidate or propofol.Neurochemical research · 2014Article
- Altered localization of the δ subunit of the GABAA receptor in the thalamus of α4 subunit knockout mice.Neurochemical research · 2014Article
- Etomidate produces similar allosteric modulation in α1β3δ and α1β3γ2L GABA(A) receptors.British journal of pharmacology · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
General anesthetics, once thought to exert their effects through non-specific membrane effects, have highly specific ion channel targets that can silence neuronal populations in the nervous system, thereby causing unconsciousness and immobility, characteristic of general anesthesia. Inhibitory GABA(A) receptors (GABA(A)Rs), particularly highly GABA-sensitive extrasynaptic receptor subtypes that give rise to sustained inhibitory currents, are uniquely sensitive to GABA(A)R-active anesthetics. A prominent population of extrasynaptic GABA(A)Rs is made up of alpha4, beta2 or beta3, and delta subunits. Considering the demonstrated importance of GABA receptor beta3 subunits for in vivo anesthetic effects of etomidate and propofol, we decided to investigate the effects of GABA anesthetics on "extrasynaptic" alpha4beta3delta and also binary alpha4beta3 receptors expressed in human embryonic kidney (HEK) cells. Consistent with previous work on similar receptor subtypes we show that maximal GABA currents through "extrasynaptic" alpha4beta3delta receptors, receptors defined by sensitivity to EtOH (30mM) and the beta-carboline beta-CCE (1microM), are enhanced by the GABA(A)R-active anesthetics etomidate, propofol, and the neurosteroid anesthetic THDOC. Furthermore, we show that receptors formed by alpha4beta3 subunits alone also show high GABA sensitivity and that saturating GABA responses of alpha4beta3 receptors are increased to the same extent by etomidate, propofol, and THDOC as are alpha4beta3delta receptors. Therefore, both alpha4beta3 and alpha4beta3delta receptors show low GABA efficacy, and GABA is also a partial agonist on certain binary alphabeta receptor subtypes. Increasing GABA efficacy on alpha4/6beta3delta and alpha4beta3 receptors is likely to make an important contribution to the anesthetic effects of etomidate, propofol and the neurosteroid THDOC.
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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.