ArticleThe Journal of pharmacology and experimental therapeutics2016
Ethanol Regulation of Synaptic GABAA α4 Receptors Is Prevented by Protein Kinase A Activation.
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 15 papers.
What it found
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Who cites it
15 citing papers in PubMed, 16 citations in OpenAlex.
- The effect of neuroimmune modulation on subjective response to alcohol in the natural environment.Alcoholism, clinical and experimental research · 2022Trial
- Integrated Network and Transcriptomic Analyses Identify a Candidate Ethanol-ADAM17 Molecular Axis Associated with Glioblastoma Progression.International journal of molecular sciences · 2026Article
- Acute Ethanol Exposure Inhibits GABA Uptake in Embryonic Chicken Retina.Neurochemical research · 2026Article
- Chronic ethanol exposure reduces resting state functional connectivity and regional synchrony in male rats.Psychopharmacology · 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
- Targeting prefrontal cortex GABAergic microcircuits for the treatment of alcohol use disorder.Frontiers in synaptic neuroscience · 2022Review
- Regulation of GABAMembranes · 2021Review
- Investigation the Relationship of Autism Spectrum Disorder andNoro psikiyatri arsivi · 2021Article
- Histone deacetylases mediate GABANeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Apremilast Alters Behavioral Responses to Ethanol in Mice: II. Increased Sedation, Intoxication, and Reduced Acute Functional Tolerance.Alcoholism, clinical and experimental research · 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
- Single Ethanol Withdrawal Regulates Extrasynaptic δ-GABAFrontiers in molecular neuroscience · 2018Article
- Synaptic targets: Chronic alcohol actions.Neuropharmacology · 2017Review
- Screening and Identification of the Host Proteins Interacting withFrontiers in microbiology · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Ethanol alters GABAA receptor trafficking and function through activation of protein kinases, and these changes may underlie ethanol dependence and withdrawal. In this study, we used subsynaptic fraction techniques and patch-clamp electrophysiology to investigate the biochemical and functional effects of protein kinase A (PKA) and protein kinase C (PKC) activation by ethanol on synaptic GABAA α4 receptors, a key target of ethanol-induced changes. Rat cerebral cortical neurons were grown for 18 days in vitro and exposed to ethanol and/or kinase modulators for 4 hours, a paradigm that recapitulates GABAergic changes found after chronic ethanol exposure in vivo. PKA activation by forskolin or rolipram during ethanol exposure prevented increases in P2 fraction α4 subunit abundance, whereas inhibiting PKA had no effect. Similarly, in the synaptic fraction, activation of PKA by rolipram in the presence of ethanol prevented the increase in synaptic α4 subunit abundance, whereas inhibiting PKA in the presence of ethanol was ineffective. Conversely, PKC inhibition in the presence of ethanol prevented the ethanol-induced increases in synaptic α4 subunit abundance. Finally, we found that either activating PKA or inhibiting PKC in the presence of ethanol prevented the ethanol-induced decrease in GABA miniature inhibitory postsynaptic current decay τ1, whereas inhibiting PKA had no effect. We conclude that PKA and PKC have opposing effects in the regulation of synaptic α4 receptors, with PKA activation negatively modulating, and PKC activation positively modulating, synaptic α4 subunit abundance and function. These results suggest potential targets for restoring normal GABAergic functioning in the treatment of alcohol use disorders.
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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.