ArticleThe Journal of physiology2006
The pre-M1 segment of the alpha1 subunit is a transduction element in the activation of the GABAA receptor.
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 19 papers.
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19 citing papers in PubMed, 45 citations in OpenAlex.
- A release of local subunit conformational heterogeneity underlies gating in a muscle nicotinic acetylcholine receptor.Nature communications · 2024Article
- Effects of glutamate and ivermectin on single glutamate-gated chloride channels of the parasitic nematode H. contortus.PLoS pathogens · 2017Article
- Mutational Analysis at Intersubunit Interfaces of an Anionic Glutamate Receptor Reveals a Key Interaction Important for Channel Gating by Ivermectin.Frontiers in molecular neuroscience · 2017Article
- Article
- Zolpidem and eszopiclone prime α1β2γ2 GABAA receptors for longer duration of activity.British journal of pharmacology · 2015Article
- GABAA receptor α and γ subunits shape synaptic currents via different mechanisms.The Journal of biological chemistry · 2014Article
- Cysteine substitutions define etomidate binding and gating linkages in the α-M1 domain of γ-aminobutyric acid type A (GABAA) receptors.The Journal of biological chemistry · 2013Article
- An outline of desensitization in pentameric ligand-gated ion channel receptors.Cellular and molecular life sciences : CMLS · 2013Review
- Agonist-specific conformational changes in the α1-γ2 subunit interface of the GABA A receptor.Molecular pharmacology · 2012Article
- Discrete M3-M4 intracellular loop subdomains control specific aspects of γ-aminobutyric acid type A receptor function.The Journal of biological chemistry · 2011Article
- Contributions of conserved residues at the gating interface of glycine receptors.The Journal of biological chemistry · 2011Article
- A mutant residue in the third transmembrane region of the GABA(A) alpha1 subunit causes increased agonistic neurosteroid responses.Neurochemistry international · 2011Article
- Higher susceptibility to halothane modulation in open- than in closed-channel alpha4beta2 nAChR revealed by molecular dynamics simulations.The journal of physical chemistry. B · 2010Article
- Gating mechanisms in Cys-loop receptors.European biophysics journal : EBJ · 2009Review
- Inverse effects on gating and modulation caused by a mutation in the M2-M3 Linker of the GABA(A) receptor gamma subunit.Molecular pharmacology · 2009Article
- Cross-linking of sites involved with alcohol action between transmembrane segments 1 and 3 of the glycine receptor following activation.Journal of neurochemistry · 2008Article
- Agonist-dependent single channel current and gating in alpha4beta2delta and alpha1beta2gamma2S GABAA receptors.The Journal of general physiology · 2008Article
- Acetylcholine receptor gating at extracellular transmembrane domain interface: the "pre-M1" linker.The Journal of general physiology · 2007Article
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3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The binding of the neurotransmitter GABA induces conformational changes in the GABAA receptor (GABAAR), leading to the opening of a gate that controls ion permeation through an integral transmembrane pore. A number of structural elements within each subunit, located near the membrane interface, are believed to undergo relative movements during this activation process. In this study, we explored the functional role of the beta-10 strand (pre-M1 segment), which connects the extracellular domain to the transmembrane domain. In alpha1beta2gamma2s GABAARs, analysis of the 12 residues of the beta-10 strand in the alpha1 subunit proximal to the first transmembrane domain identified two residues, alpha1V212 and alpha1K220, in which mutations produced rightward shifts in the GABA concentration-response relationship and also reduced the relative efficacy of the partial agonist, piperidine-4-sulphonic acid. Ultra-fast agonist techniques were applied to mutant alpha1(K220A)beta2gamma2s GABAARs and revealed that the macroscopic functional deficit in this mutant could be attributed to a slowing of the opening rate constant, from approximately 1500 s(-1) in wild-type (WT) channels to approximately 730 s(-1) in the mutant channels, and a reduction in the time spent in the active state for the mutant. These changes were accompanied by a decrease in agonist affinity, with half-maximal activation rates achieved at 0.77 mM GABA in WT and 1.4 mM GABA in the alpha1(K220A)beta2gamma2s channels. The beta-10 strand (pre-M1 segment) emerges, from this and other studies, as a key functional component in the activation of the GABAAR.
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