ArticleThe Journal of pharmacology and experimental therapeutics2016
Regulation of Extrasynaptic GABAA α4 Receptors by Ethanol-Induced Protein Kinase A, but Not Protein Kinase C Activation in Cultured Rat Cerebral Cortical Neurons.
Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Acute Ethanol Exposure Inhibits GABA Uptake in Embryonic Chicken Retina.Neurochemical research · 2026Article
- Divergent Population-Specific Effects of Chronic Ethanol Exposure on Excitability and Inhibitory Transmission in Male and Female Rat Central Amygdala.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Apremilast-induced increases in acute ethanol intoxication and decreases in ethanol drinking in mice involve PKA phosphorylation of GABANeuropharmacology · 2022Article
- Targeting prefrontal cortex GABAergic microcircuits for the treatment of alcohol use disorder.Frontiers in synaptic neuroscience · 2022Review
- Regulation of GABAMembranes · 2021Review
- GPR30 receptor promotes preoperative anxiety-induced postoperative hyperalgesia by up-regulating GABABMC anesthesiology · 2020Article
- A Rationale for Allopregnanolone Treatment of Alcohol Use Disorders: Basic and Clinical Studies.Alcoholism, clinical and experimental research · 2020Review
- The Functional Role of Spontaneously Opening GABAFrontiers in molecular neuroscience · 2019Article
- Feature Article: Selective modulation of tonically active GABAExperimental biology and medicine (Maywood, N.J.) · 2018Article
- Maternal care-related differences in males and females rats' sensitivity to ethanol and the associations between the GABAergic system and steroids in males.Developmental psychobiology · 2018Article
- GABA type a receptor trafficking and the architecture of synaptic inhibition.Developmental neurobiology · 2018Review
- The Mammalian Circadian Clock Exhibits Chronic Ethanol Tolerance and Withdrawal-Induced Glutamate Hypersensitivity, Accompanied by Changes in Glutamate and TrkB Receptor Proteins.Alcoholism, clinical and experimental research · 2018Article
- Single Ethanol Withdrawal Regulates Extrasynaptic δ-GABAFrontiers in molecular neuroscience · 2018Article
- Missense Gamma-Aminobutyric Acid Receptor Polymorphisms Are Associated with Reaction Time, Motor Time, and Ethanol EffectsFrontiers in cellular neuroscience · 2018Article
- Synaptic targets: Chronic alcohol actions.Neuropharmacology · 2017Review
- Differential regulation of synaptic and extrasynaptic α4 GABA(A) receptor populations by protein kinase A and protein kinase C in cultured cortical neurons.Neuropharmacology · 2016Article
- Ethanol Regulation of Synaptic GABAA α4 Receptors Is Prevented by Protein Kinase A Activation.The Journal of pharmacology and experimental therapeutics · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Ethanol produces changes in GABAA receptor trafficking and function that contribute to ethanol dependence symptomatology. Extrasynaptic γ-aminobutyric acid A receptors (GABAA-R) mediate inhibitory tonic current and are of particular interest because they are potentiated by physiologically relevant doses of ethanol. Here, we isolate GABAA α4δ receptors by western blotting in subsynaptic fractions to investigate protein kinase A (PKA) and protein kinase C (PKC) modulation of ethanol-induced receptor trafficking, while extrasynaptic receptor function is determined by measurement of tonic inhibition and responses evoked by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). Rat cerebral cortical neurons were grown for 18 days in vitro and exposed to ethanol and/or PKA/PKC modulators. Ethanol exposure (1 hour) did not alter GABAA α4 receptor abundance, but it increased tonic current amplitude, an effect that was prevented by inhibiting PKA, but not PKC. Direct activation of PKA, but not PKC, increased the abundance and tonic current of extrasynaptic α4δ receptors. In contrast, prolonged ethanol exposure (4 hours) reduced α4δ receptor abundance as well as tonic current, and this effect was also PKA dependent. Finally, PKC activation by ethanol or phorbol-12,13-dibutyrate (PdBu) had no effect on extrasynaptic α4δ subunit abundance or activity. We conclude that ethanol alters extrasynaptic α4δ receptor function and expression in cortical neurons in a PKA-dependent manner, but ethanol activation of PKC does not influence these receptors. These results could have clinical relevance for therapeutic strategies to restore normal GABAergic functioning for the treatment of alcohol use disorders.
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