ArticleThe Journal of physiology2006
Modes and models of GABA(A) receptor gating.
Article in The Journal of physiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- The relationship between apparent potentiation and the magnitude of the control response.The Journal of general physiology · 2026Article
- Null method to estimate the maximal PA at subsaturating concentrations of agonist.The Journal of general physiology · 2025Article
- Potentiation of the GABABiophysical journal · 2024Article
- Shisa7-Dependent Regulation of GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- αACS chemical neuroscience · 2022Article
- Computational models of neurotransmission at cerebellar synapses unveil the impact on network computation.Frontiers in computational neuroscience · 2022Review
- Mutations at the M2 and M3 Transmembrane Helices of the GABAACS chemical neuroscience · 2021Article
- αACS chemical neuroscience · 2021Article
- Heterogeneous expression of GABA receptor-like subunits LCCH3 and GRD reveals functional diversity of GABA receptors in the honeybee Apis mellifera.British journal of pharmacology · 2020Article
- Applying the Monod-Wyman-Changeux Allosteric Activation Model to Pseudo-Steady-State Responses from GABAMolecular pharmacology · 2019Review
- GABA Type A Receptor Activation in the Allosteric Coagonist Model Framework: Relationship between ECMolecular pharmacology · 2018Article
- The Actions of Drug Combinations on the GABAMolecular pharmacology · 2017Article
- Effects of glutamate and ivermectin on single glutamate-gated chloride channels of the parasitic nematode H. contortus.PLoS pathogens · 2017Article
- Comparison of Steroid Modulation of Spontaneous Inhibitory Postsynaptic Currents in Cultured Hippocampal Neurons and Steady-State Single-Channel Currents from Heterologously Expressed α1β2γ2L GABA(A) Receptors.Molecular pharmacology · 2016Article
- Modal gating of endplate acetylcholine receptors: A proposed mechanism.The Journal of general physiology · 2015Article
- Contrasting actions of a convulsant barbiturate and its anticonvulsant enantiomer on the α1 β3 γ2L GABAA receptor account for their in vivo effects.The Journal of physiology · 2015Article
- Modal affinities of endplate acetylcholine receptors caused by loop C mutations.The Journal of general physiology · 2015Article
- Zolpidem and eszopiclone prime α1β2γ2 GABAA receptors for longer duration of activity.British journal of pharmacology · 2015Article
- Exploring the mechanism of general anesthesia: kinetic analysis of GABAA receptor electrophysiology.Biophysical journal · 2015Article
- Co-expression of γ2 subunits hinders processing of N-linked glycans attached to the N104 glycosylation sites of GABAA receptor β2 subunits.Neurochemical research · 2014Article
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2 authors.
Funding
Abstract
Upon activation by agonist, the type A gamma-aminobutyric acid receptor (GABAR) 'gates', allowing chloride ions to permeate membranes and produce fast inhibition of neurons. There is no consensus kinetic model for the GABAR gating mechanism. We expressed human alpha(1)beta(1)gamma(2S) GABARs in HEK 293 cells and recorded single channel currents in the cell-attached configuration using various GABA concentrations (50-5000 microm). Closed and open events occurred individually and in clusters that had at least three different modes that were distinguishable by open probability (P(O)): High (P(O)= 0.73), Mid (P(O)= 0.50), and Low (P(O)= 0.21). We used a critical time to isolate shorter bursts of openings and to thus eliminate long-lived, desensitized events. Bursts from all three modes contained three closed and three open components. We employed maximum likelihood fitting, autocorrelation analysis and macroscopic current simulation to distinguish kinetic schemes. The 'core' gating scheme for most models contained two closed states that preceded an open state (C(1) C(2) O(1)). The two best-fitting models had a third closed state connected to C(1) and a second open state (O(2)) connected to C(2). The third open state, whose occupancy varied greatly between modes, could be connected either to O(2) or C(2). We estimated rate constants for two identical, independent GABA binding steps by globally fitting data across GABA concentrations ranging from 50 to 1000 microm. For the most highly ranked model the binding rate constants were: k(+)= 3 microm(-1) s(-1) and k(-)= 272 s(-1) (K(D)= 91 microm).
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