Evidence map›Paper›PMID 25887256›Full record

ArticleBMC neuroscience2015

Pharmacological characterisation of murine α4β1δ GABAA receptors expressed in Xenopus oocytes.

Inge S Villumsen, Petrine Wellendorph, Trevor G Smart

Abstract read
In one paragraph

Article in BMC neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Copper signalling: causes and consequences.Cell communication and signaling : CCS · 2018
    Review
  2. Zinc Selectively Blocks Neurosteroid-Sensitive Extrasynaptic δGABAA Receptors in the Hippocampus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016
    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

3 authors.

Inge S VillumsenDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK. inge_villumsen@hotmail.com.
Petrine WellendorphDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Fruebjergvej 3, 2100, Copenhagen, Denmark. pw@sund.ku.dk.
Trevor G SmartDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK. t.smart@ucl.ac.uk.

Funding

Medical Research Council MR/K005537/1
6 · The paper itself

Abstract

backgroundGABAA receptor subunit composition has a profound effect on the receptor's physiological and pharmacological properties. The receptor β subunit is widely recognised for its importance in receptor assembly, trafficking and post-translational modifications, but its influence on extrasynaptic GABAA receptor function is less well understood. Here, we examine the pharmacological properties of a potentially native extrasynaptic GABAA receptor that incorporates the β1 subunit, specifically composed of α4β1δ and α4β1 subunits.

resultsGABA activated concentration-dependent responses at α4β1δ and α4β1 receptors with EC50 values in the nanomolar to micromolar range, respectively. The divalent cations Zn(2+) and Cu(2+), and the β1-selective inhibitor salicylidine salicylhydrazide (SCS), inhibited GABA-activated currents at α4β1δ receptors. Surprisingly the α4β1 receptor demonstrated biphasic sensitivity to Zn(2+) inhibition that may reflect variable subunit stoichiometries with differing sensitivity to Zn(2+). The neurosteroid tetrahydro-deoxycorticosterone (THDOC) significantly increased GABA-initiated responses in concentrations above 30 nM for α4β1δ receptors.

conclusionsWith this study we report the first pharmacological characterisation of various GABAA receptor ligands acting at murine α4β1δ GABAA receptors, thereby improving our understanding of the molecular pharmacology of this receptor isoform. This study highlights some notable differences in the pharmacology of murine and human α4β1δ receptors. We consider the likelihood that the α4β1δ receptor may play a role as an extrasynaptic GABAA receptor in the nervous system.

Indexed as

AnimalsCations, DivalentCopperDesoxycorticosteroneDose-Response Relationship, DrugGABA-A Receptor AgonistsGABA-A Receptor Antagonistsgamma-Aminobutyric AcidMiceOocytesPatch-Clamp TechniquesRatsReceptors, GABA-AXenopus laevisZincCations, DivalentCopperDesoxycorticosteroneGABA-A Receptor AgonistsGABA-A Receptor AntagonistsGabra4 protein, mouseGabrb1 protein, mouseGabrd protein, ratgamma-Aminobutyric AcidReceptors, GABA-AtetrahydrodeoxycorticosteroneZinc

Identifiers

PMID25887256
PMCPMC4359537

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.