ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Benzodiazepines modulate GABAA receptors by regulating the preactivation step after GABA binding.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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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
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Use of Drugs Affecting GABAMolecular neurobiology · 2025Pooled it
- Computational investigation of circuit mechanisms underlying short-latency responses to cortical stimulation.bioRxiv : the preprint server for biology · 2026Article
- Synaptic correlates of benzodiazepine tolerance.Molecular psychiatry · 2026Review
- The relationship between apparent potentiation and the magnitude of the control response.The Journal of general physiology · 2026Article
- Long-term treatment with benzodiazepines and related Z-drugs exacerbates breast cancer: clinical evidence and molecular mechanisms.Cellular & molecular biology letters · 2025Article
- Chronic benzodiazepine treatment triggers gephyrin scaffold destabilization and GABAFrontiers in cellular neuroscience · 2025Article
- GABAJournal of neurochemistry · 2024Review
- State-dependent energetics of GABABiophysical journal · 2024Article
- Potentiation of the GABABiophysical journal · 2024Article
- Inhibitory and excitatory synaptic neuroadaptations in the diazepam tolerant brain.Neurobiology of disease · 2023Article
- Delayed tezampanel and caramiphen treatment but not midazolam protects against long-term neuropathology after soman exposure.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Effect of Preoperative Antianxiety Medications on Blood Pressure and Blood Loss in Total Knee Arthroplasty: A Case-Control Study.Advances in orthopedics · 2023Article
- Benzodiazepine Modulation of GABABiomolecules · 2022Review
- Shisa7-Dependent Regulation of GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
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- Computational models of neurotransmission at cerebellar synapses unveil the impact on network computation.Frontiers in computational neuroscience · 2022Review
- A Comparison of Epileptogenic Effect of Status Epilepticus Treated With Diazepam, Midazolam, and Pentobarbital in the Mouse Pilocarpine Model of Epilepsy.Frontiers in neurology · 2022Article
- Electrophysiology of ionotropic GABA receptors.Cellular and molecular life sciences : CMLS · 2021Review
- Direct Structural Insights into GABATrends in biochemical sciences · 2021Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
GABA(A) receptors (GABA(A)Rs) composed of αβγ subunits are allosterically modulated by the benzodiazepines (BDZs). Agonists at the BDZ binding site potentiate submaximal GABA responses by increasing the apparent affinity of GABA(A)Rs for GABA. Although BDZs were initially thought to affect the binding of GABA agonists, recent studies suggest an effect on receptor gating; however, the involvement of preactivation steps in the modulation by BDZs has not been considered. Consequently, we examined whether BDZ agonists could exert their modulatory effect by displacing the equilibrium between resting and preactivated states of recombinant α1β2γ2 GABA(A)Rs expressed in Xenopus oocytes. For GABA and the partial agonists 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol and piperidine-4-sulfonic acid, we examined BDZ modulation using a simple three-step model incorporating agonist binding, receptor preactivation, and channel opening. The model accounted for diazepam modulation simply by increasing the preactivation constant by approximately fourfold. To assess whether BDZs preferentially affected a specific GABA binding site, pentameric concatamers were used. This demonstrated that single GABA-binding site mutant receptors were equally sensitive to modulation by BDZs compared with wild-type counterparts. Overall, our results suggest that BDZs affect the preactivation step to cause a global conformational rearrangement of GABA(A)Rs, thereby modulating receptor function.
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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.