ArticleBrain research2012
Regulation of the surface expression of α4β2δ GABAA receptors by high efficacy states.
Article in Brain research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Sex differences in resilience at puberty depend upon divergent effects of a stress steroid at α4βδ GABABrain research · 2025Article
- The role of the neuroinflammation and stressors in premenstrual syndrome/premenstrual dysphoric disorder: a review.Frontiers in endocrinology · 2025Review
- Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development.Frontiers in psychiatry · 2023Review
- The role of flumazenil in generalised anxiety disorder: a pilot naturalistic open-label study with a focus on treatment resistance.Therapeutic advances in psychopharmacology · 2023Article
- Long-Term Management of Generalised Anxiety Disorder with Low-Dose Continuous Infusions of Flumazenil: A Case Series.Behavioral sciences (Basel, Switzerland) · 2022Article
- Allopregnanolone in postpartum depression: Role in pathophysiology and treatment.Neurobiology of stress · 2020Review
- Pubertal hormones increase hippocampal expression of α4βδ GABANeuroscience letters · 2019Article
- Role of α4-containing GABABrain research · 2017Article
- Flumazenil decreases surface expression of α4β2δ GABAA receptors by increasing the rate of receptor internalization.Brain research bulletin · 2016Article
- Neurosteroid effects at α4βδ GABAA receptors alter spatial learning and synaptic plasticity in CA1 hippocampus across the estrous cycle of the mouse.Brain research · 2015Article
- The role of ovarian hormone-derived neurosteroids on the regulation of GABAA receptors in affective disorders.Psychopharmacology · 2014Review
- Characterization of neurosteroid effects on hyperpolarizing current at α4β2δ GABAA receptors.Psychopharmacology · 2014Article
- Effect of low doses of progesterone in the expression of the GABA(A) receptor α4 subunit and procaspase-3 in the hypothalamus of female rats.Endocrine · 2014Article
- The role of the δ GABA(A) receptor in ovarian cycle-linked changes in hippocampus-dependent learning and memory.Neurochemical research · 2014Article
- A stress steroid triggers anxiety via increased expression of α4βδ GABAA receptors in methamphetamine dependence.Neuroscience · 2013Article
- Neurosteroid interactions with synaptic and extrasynaptic GABA(A) receptors: regulation of subunit plasticity, phasic and tonic inhibition, and neuronal network excitability.Psychopharmacology · 2013Review
- The influence of stress at puberty on mood and learning: role of the α4βδ GABAA receptor.Neuroscience · 2013Review
- GABAA receptor membrane insertion rates are specified by their subunit composition.Molecular and cellular neurosciences · 2013Article
- Estrous cycle regulation of extrasynaptic δ-containing GABA(A) receptor-mediated tonic inhibition and limbic epileptogenesis.The Journal of pharmacology and experimental therapeutics · 2013Article
- Altered gamma oscillations during pregnancy through loss of δ subunit-containing GABA(A) receptors on parvalbumin interneurons.Frontiers in neural circuits · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
α4βδ GABA(A) receptors (GABARs) have low CNS expression, but their expression is increased by 48h exposure to the neurosteroid THP (3α-OH-5α[β]-pregnan-20-one). THP also increases the efficacy of δ-containing GABARs acutely, where GABA is a partial agonist. Thus, we examined effects of THP (100 nM) and full GABA agonists at α4β2δ (gaboxadol, 10 μM, and β-alanine, 10 μM-1mM), on surface expression of α4β2δ. To this end, we used an α4 construct tagged with a 3XFLAG (F) epitope or measured expression of native α4 and δ. HEK-293 cells or cultured hippocampal neurons were transfected with α4Fβ2δ and treated 24h later with GABA agonists, THP, GABA plus THP or vehicle (0.01% DMSO) for 0.5 h-48 h. Immunocytochemistry was performed under both non-permeabilized and permeabilized conditions to detect surface and intracellular labeling, respectively, using confocal microscopy. The high efficacy agonists and GABA (1 or 10 μM) plus THP increased α4β2δ surface expression up to 3-fold after 48h, an effect first seen by 0.5h. This effect was not dependent upon the polarity of GABAergic current, although expression was increased by KCC2. Intracellular labeling was decreased while functional expression was confirmed by whole cell patch clamp recordings of responses to GABA agonists. GABA plus THP treatment did not alter the rate of receptor removal from the surface membrane, suggesting that THP-induced α4β2δ expression is likely via receptor insertion. Surface expression of α4β2δ was decreased by rottlerin (10 μM), suggesting a role for PKC-δ. These results suggest that trafficking of α4β2δ GABARs is regulated by high efficacy states.
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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.