Evidence map›Paper›PMID 25274824›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014

EAAT2 (GLT-1; slc1a2) glutamate transporters reconstituted in liposomes argues against heteroexchange being substantially faster than net uptake.

Yun Zhou, Xiaoyu Wang, Anastasios V Tzingounis, Niels C Danbolt, H Peter Larsson

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.1field-weighted citation impact, top 15% 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

22 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
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  5. TargetingInternational journal of molecular sciences · 2024
    Review
  6. Alterations in Astrocytic Regulation of Excitation and Inhibition by Stress Exposure and in Severe Psychopathology.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022
    Review
  7. Review
  8. Control of complex behavior by astrocytes and microglia.Neuroscience and biobehavioral reviews · 2022
    Review
  9. Review
  10. Review
  11. Allosteric gate modulation confers KThe EMBO journal · 2019
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Astroglial Glutamate Signaling and Uptake in the Hippocampus.Frontiers in molecular neuroscience · 2017
    Review
  17. GLT-1: The elusive presynaptic glutamate transporter.Neurochemistry international · 2016
    Review
  18. Review
  19. 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

5 authors at 3 institutions in 2 countries.

Yun ZhouDepartment of Anatomy, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
Xiaoyu WangDepartment of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, Florida 33136, and.
Anastasios V TzingounisDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269.ORCID http://orcid.org/0000-0002-4605-3437
Niels C DanboltDepartment of Anatomy, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway, PLarsson@med.miami.edu n.c.danbolt@medisin.uio.no.
H Peter LarssonDepartment of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, Florida 33136, and PLarsson@med.miami.edu n.c.danbolt@medisin.uio.no.
University of Miami · USUniversity of Oslo · NOUniversity of Connecticut · US

Funding

Modulation of KCNQ1 channel activityR01GM109762 · NIGMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI KASS, ROBERT S, LARSSON, HANS PETER · 2014 to 2022
$3.1M
Cellular physiology of epilepsy-associated KCNQ2 channelsR01NS073981 · NINDS · UNIVERSITY OF CONNECTICUT STORRS · PI TZINGOUNIS, ANASTASIOS · 2011 to 2015
$1.6M
Molecular mechanisms of voltage-gated proton channelsR01HL095920 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI LARSSON, HANS PETER · 2010 to 2013
$1.5M
Molecular mechanisms of glutamate transportersR01NS051169 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI LARSSON, HANS PETER · 2005 to 2008
$1.2M
CELLULAR PHYSIOLOGY OF EPILEPSY-ASSOCIATED KCNQ2 and KCNQ3 CHANNELSR56NS073981 · NINDS · UNIVERSITY OF CONNECTICUT STORRS · PI TZINGOUNIS, ANASTASIOS · 2016 to 2016
$388k
NHLBI NIH HHS R01 HL095920NHLBI NIH HHS R01-HL095920NIGMS NIH HHS R01 GM109762NINDS NIH HHS NS073981NINDS NIH HHS R01 NS051169NINDS NIH HHS R01 NS073981NINDS NIH HHS R56 NS073981
6 · The paper itself

Abstract

The EAAT2 glutamate transporter, accounts for >90% of hippocampal glutamate uptake. Although EAAT2 is predominantly expressed in astrocytes, ∼10% of EAAT2 molecules are found in axon terminals. Despite the lower level of EAAT2 expression in glutamatergic terminals, when hippocampal slices are incubated with low concentration of d-aspartate (an EAAT2 substrate), axon terminals accumulate d-aspartate as quickly as astroglia. This implies an unexplained mismatch between the distribution of EAAT2 protein and of EAAT2-mediated transport activity. One hypothesis is that (1) heteroexchange of internal substrate with external substrate is considerably faster than net uptake and (2) terminals favor heteroexchange because of high levels of internal glutamate. However, it is currently unknown whether heteroexchange and uptake have similar or different rates. To address this issue, we used a reconstituted system to compare the relative rates of the two processes in rat and mice. Net uptake was sensitive to changes in the membrane potential and was stimulated by external permeable anions in agreement with the existence of an uncoupled anion conductance. By using the latter, we also demonstrate that the rate of heteroexchange also depends on the membrane potential. Additionally, our data further suggest the presence of a sodium leak in EAAT2. By incorporating the new findings in our previous model of glutamate uptake by EAAT2, we predict that the voltage sensitivity of exchange is caused by the voltage-dependent third Na(+) binding. Further, both our experiments and simulations suggest that the relative rates of net uptake and heteroexchange are comparable in EAAT2.

Indexed as

Amino AcidsAnimalsBrainCattleComputer SimulationExcitatory Amino Acid Transporter 2Glutamic AcidIn Vitro TechniquesIonophoresLiposomesMembrane PotentialsMiceMice, Inbred C57BLMice, TransgenicModels, BiologicalPotassiumAmino AcidsExcitatory Amino Acid Transporter 2Glutamic AcidIonophoresLiposomesPotassiumValinomycinglutamate uptakeliposomesmembrane protein purificationneuronal glutamate uptakeneurotransmitter transporttransport kinetics

Identifiers

PMID25274824
PMCPMC4180478
OpenAlexW2038845814

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.