Evidence map›Paper›PMID 25238745›Full record

ArticleMolecular pharmacology2014

γ-aminobutyric acid type A α4, β2, and δ subunits assemble to produce more than one functionally distinct receptor type.

Megan M Eaton, John Bracamontes, Hong-Jin Shu, Ping Li, Steven Mennerick, Joe Henry Steinbach, Gustav Akk

Open access · bronzeAbstract read
In one paragraph

Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

27 citing papers in PubMed, 37 citations in OpenAlex.

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  13. Chemogenetic Isolation Reveals Synaptic Contribution of δ GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018
    Article
  14. Article
  15. Comparison of αβδ and αβγ GABAPharmacological research · 2018
    Review
  16. Article
  17. Article
  18. Article
  19. Immunochemical Localization of GABANeurochemical research · 2016
    Article
  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

7 authors at 1 institution.

Megan M EatonDepartment of Anesthesiology (M.M.E., J.B., P.L., J.H.S., G.A.), Department of Psychiatry (H.-J.S., S.M.), and Taylor Family Institute for Innovative Psychiatric Research (S.M., J.H.S., G.A.), Washington University School of Medicine, St. Louis, Missouri.
John BracamontesDepartment of Anesthesiology (M.M.E., J.B., P.L., J.H.S., G.A.), Department of Psychiatry (H.-J.S., S.M.), and Taylor Family Institute for Innovative Psychiatric Research (S.M., J.H.S., G.A.), Washington University School of Medicine, St. Louis, Missouri.
Hong-Jin ShuDepartment of Anesthesiology (M.M.E., J.B., P.L., J.H.S., G.A.), Department of Psychiatry (H.-J.S., S.M.), and Taylor Family Institute for Innovative Psychiatric Research (S.M., J.H.S., G.A.), Washington University School of Medicine, St. Louis, Missouri.
Ping LiDepartment of Anesthesiology (M.M.E., J.B., P.L., J.H.S., G.A.), Department of Psychiatry (H.-J.S., S.M.), and Taylor Family Institute for Innovative Psychiatric Research (S.M., J.H.S., G.A.), Washington University School of Medicine, St. Louis, Missouri.
Steven MennerickDepartment of Anesthesiology (M.M.E., J.B., P.L., J.H.S., G.A.), Department of Psychiatry (H.-J.S., S.M.), and Taylor Family Institute for Innovative Psychiatric Research (S.M., J.H.S., G.A.), Washington University School of Medicine, St. Louis, Missouri.
Joe Henry SteinbachDepartment of Anesthesiology (M.M.E., J.B., P.L., J.H.S., G.A.), Department of Psychiatry (H.-J.S., S.M.), and Taylor Family Institute for Innovative Psychiatric Research (S.M., J.H.S., G.A.), Washington University School of Medicine, St. Louis, Missouri.
Gustav AkkDepartment of Anesthesiology (M.M.E., J.B., P.L., J.H.S., G.A.), Department of Psychiatry (H.-J.S., S.M.), and Taylor Family Institute for Innovative Psychiatric Research (S.M., J.H.S., G.A.), Washington University School of Medicine, St. Louis, Missouri akk@morpheus.wustl.edu.
Taylor Family Institute for Innovative Psychiatric Research

Funding

STRUCTURE/ACTIVITY STUDIES OF NEUROSTEROID ANALOGUESP01GM047969 · NIGMS · WASHINGTON UNIVERSITY · PI COVEY, DOUGLAS F · 1992 to 2011
$18.7M
CONTROL OF SYNAPTIC GLUTAMATE RELEASER01MH078823 · NIMH · WASHINGTON UNIVERSITY · PI MENNERICK, STEVEN J · 2006 to 2015
$3.2M
SYNERGISTIC ACTIONS OF INTRAVENOUS ANESTHETICSR01GM108580 · NIGMS · WASHINGTON UNIVERSITY · PI AKK, GUSTAV · 2014 to 2021
$2.4M
RECEPTOR POPULATIONS UNDERLYING TONIC GABA CURRENTS IN HIPPOCAMPUSR21MH099658 · NIMH · WASHINGTON UNIVERSITY · PI MENNERICK, STEVEN J · 2013 to 2014
$418k
NIGMS NIH HHS P01 GM047969NIGMS NIH HHS P01-GM047969NIGMS NIH HHS R01 GM108580NIGMS NIH HHS R01-GM108580NIMH NIH HHS R01 MH078823NIMH NIH HHS R01-MH078823NIMH NIH HHS R21 MH099658NIMH NIH HHS R21-MH099658
6 · The paper itself

Abstract

Native γ-aminobutyric acid (GABA)A receptors consisting of α4, β1-3, and δ subunits mediate responses to the low, tonic concentration of GABA present in the extracellular milieu. Previous studies on heterologously expressed α4βδ receptors have shown a large degree of variability in functional properties, including sensitivity to the transmitter. We studied properties of α4β2δ receptors employing free subunits and concatemeric constructs, expressed in Xenopus oocytes, HEK 293 cells, and cultured hippocampal neurons. The expression system had a strong effect on the properties of receptors containing free subunits. The midpoint of GABA activation curve was 10 nM for receptors in oocytes versus 2300 nM in HEK cells. Receptors activated by the steroid alfaxalone had an estimated maximal open probability of 0.6 in oocytes and 0.01 in HEK cells. Irrespective of the expression system, receptors resulting from combining the tandem construct β2-δ and a free α4 subunit exhibited large steroid responses. We propose that free α4, β2, and δ subunits assemble in different configurations with distinct properties in oocytes and HEK cells, and that subunit linkage can overcome the expression system-dependent preferential assembly of free subunits. Hippocampal neurons transfected with α4 and the picrotoxin-resistant δ(T269Y) subunit showed large responses to alfaxalone in the presence of picrotoxin, suggesting that α4βδ receptors may assemble in a similar configuration in neurons and oocytes.

Indexed as

AnimalsDose-Response Relationship, Druggamma-Aminobutyric AcidHEK293 CellsHippocampusHumansPregnanedionesProtein SubunitsRatsRats, Sprague-DawleyReceptors, GABA-AXenopus laevisalphaxalonegamma-Aminobutyric AcidPregnanedionesProtein SubunitsReceptors, GABA-A

Identifiers

PMID25238745
PMCPMC4244592
OpenAlexW2313915838

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.