Evidence map›Paper›PMID 23408117›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2013

Ethanol activation of protein kinase A regulates GABAA α1 receptor function and trafficking in cultured cerebral cortical neurons.

Stephen L Carlson, Sandeep Kumar, David F Werner, Christopher E Comerford, A Leslie Morrow

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.8field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Review
  3. Regulation of GABAMembranes · 2021
    Review
  4. Article
  5. Histone deacetylases mediate GABANeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018
    Article
  6. Article
  7. Ethanol Exposure RegulatesThe Journal of pharmacology and experimental therapeutics · 2017
    Article
  8. Article
  9. Article
  10. Ethanol Regulation of Synaptic GABAA α4 Receptors Is Prevented by Protein Kinase A Activation.The Journal of pharmacology and experimental therapeutics · 2016
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Stephen L CarlsonBowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Sandeep Kumar
David F Werner
Christopher E Comerford
A Leslie Morrow
University of North Carolina at Chapel Hill · US

Funding

UNC ARC Information/Dissemination CoreP60AA011605 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Thomas L. Kash · 2003 to 2026
$46.3M
Supplement to Molecular and Cellular Studies on Alcohol's ActionsT32AA007573 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FULTON T CREWS, Thomas L. Kash · 1997 to 2026
$9.3M
MOLECULAR AND CELLULAR PATHOGENESIS IN ALCOHOLISMP50AA011605 · NIAAA · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI BREESE, GEORGE R · 1998 to 2002
$4.9M
Ethanol Regulation of GABAalpha receptorsK01AA015409 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KUMAR, SANDEEP · 2005 to 2009
$515k
NIAAA NIH HHS AA007573NIAAA NIH HHS AA011605NIAAA NIH HHS AA015409NIAAA NIH HHS K01 AA015409NIAAA NIH HHS P50 AA011605NIAAA NIH HHS P60 AA011605NIAAA NIH HHS T32 AA007573
6 · The paper itself

Abstract

Ethanol exposure produces alterations in GABAergic signaling that are associated with dependence and withdrawal. Previously, we demonstrated that ethanol-induced protein kinase C (PKC) γ signaling selectively contributes to changes in GABAA α1 synaptic receptor activity and surface expression. Here, we demonstrate that protein kinase A (PKA) exerts opposing effects on GABAA receptor adaptations during brief ethanol exposure. Cerebral cortical neurons from day 0-1 rat pups were tested after 18 days in culture. Receptor trafficking was assessed by Western blot analysis, and functional changes were measured using whole-cell patch-clamp recordings of evoked and miniature inhibitory postsynaptic current (mIPSC) responses. One-hour ethanol exposure increased membrane-associated PKC and PKA, but steady-state GABAA α1 subunit levels were maintained. Activation of PKA by Sp-adenosine 3',5'-cyclic monophosphothioate triethylamine alone increased GABAA α1 subunit surface expression and zolpidem potentiation of GABA responses, whereas coexposure of ethanol with the PKA inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate triethylamine decreased α1 subunit expression and zolpidem responses. Exposure to the PKC inhibitor calphostin-C with ethanol mimicked the effect of direct PKA activation. The effects of PKA modulation on mIPSC decay τ were consistent with its effects on GABA currents evoked in the presence of zolpidem. Overall, the results suggest that PKA acts in opposition to PKC on α1-containing GABAA receptors, mediating the GABAergic effects of ethanol exposure, and may provide an important target for the treatment of alcohol dependence/withdrawal.

Indexed as

ActinsAnimalsBiotinylationBlotting, WesternCells, CulturedCentral Nervous System DepressantsCerebral CortexCyclic AMP-Dependent Protein KinasesElectrophysiological PhenomenaEnzyme ActivationEnzyme InhibitorsEthanolExcitatory Postsynaptic PotentialsFemaleGABA AgonistsMaleActinsCentral Nervous System DepressantsCyclic AMP-Dependent Protein KinasesEnzyme InhibitorsEthanolGABA AgonistsGabra1 protein, ratProtein Kinase CPyridinesReceptors, GABA-AZolpidem

Identifiers

PMID23408117
PMCPMC3629799
OpenAlexW2142204999

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.