Evidence map›Paper›PMID 25944186›Full record

ArticleGlia2015

Aquaporin-4 regulates the velocity and frequency of cortical spreading depression in mice.

Xiaoming Yao, Alex J Smith, Byung-Ju Jin, Zsolt Zador, Geoffrey T Manley, A S Verkman

Open access · greenAbstract read
In one paragraph

Article in Glia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

12 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
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  9. Microglia alter the threshold of spreading depolarization and related potassium uptake in the mouse brain.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020
    Article
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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

6 authors at 2 institutions in 1 country.

Xiaoming YaoDepartment of Medicine and Physiology, University of California, San Francisco, California, 94143.
Alex J SmithDepartment of Medicine and Physiology, University of California, San Francisco, California, 94143.
Byung-Ju JinDepartment of Medicine and Physiology, University of California, San Francisco, California, 94143.
Zsolt ZadorDepartment of Neurological Surgery, University of California, San Francisco, California, 94143.
Geoffrey T ManleyDepartment of Neurological Surgery, University of California, San Francisco, California, 94143.
A S VerkmanDepartment of Medicine and Physiology, University of California, San Francisco, California, 94143.
University of California, San Francisco · USNeurological Surgery · US

Funding

SynthesisP30DK072517 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2005 to 2022
$18.1M
Functional Role of Aquaporins in Eye PhysiologyR01EY013574 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2002 to 2022
$7.6M
MECHANISMS OF WATER TRANSPORT IN RENAL EPITHELIAR37DK035124 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 1999 to 2008
$4.2M
Application of Novel Optical Methods to Cell DynamicsR37EB000415 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2007 to 2016
$4.1M
Application of Novel Optical Methods to Cell DynamicsR01EB000415 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2002 to 2006
$1.7M
Role of Aquaporin-4 Water Channels in Cerebral EdemaR01NS050173 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MANLEY, GEOFFREY T · 2005 to 2009
$1.5M
WATER AND NON-ELECTROLYTE TRANSPORT IN RENAL VESICLESR01DK035124 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 1986 to 2014
$1.4M
APPLICATION OF NOVEL OPTICAL METHODS TO CELL DYNAMICSR01DK043840 · NIDDK · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI VERKMAN, ALAN S · 1993 to 2001
$494k
NEI NIH HHS EY13574NEI NIH HHS R01 EY013574NIBIB NIH HHS EB00415NIBIB NIH HHS R01 EB000415NIBIB NIH HHS R37 EB000415NIDDK NIH HHS DK35124NIDDK NIH HHS DK43840NIDDK NIH HHS DK72517NIDDK NIH HHS P30 DK072517NIDDK NIH HHS R01 DK035124NIDDK NIH HHS R37 DK035124NINDS NIH HHS NS50173NINDS NIH HHS R01 NS050173
6 · The paper itself

Abstract

The astrocyte water channel aquaporin-4 (AQP4) regulates extracellular space (ECS) K(+) concentration ([K(+)]e) and volume dynamics following neuronal activation. Here, we investigated how AQP4-mediated changes in [K(+)]e and ECS volume affect the velocity, frequency, and amplitude of cortical spreading depression (CSD) depolarizations produced by surface KCl application in wild-type (AQP4(+/+)) and AQP4-deficient (AQP4(-/-)) mice. In contrast to initial expectations, both the velocity and the frequency of CSD were significantly reduced in AQP4(-/-) mice when compared with AQP4(+/+) mice, by 22% and 32%, respectively. Measurement of [K(+)]e with K(+)-selective microelectrodes demonstrated an increase to ∼35 mM during spreading depolarizations in both AQP4(+/+) and AQP4(-/-) mice, but the rates of [K(+)]e increase (3.5 vs. 1.5 mM/s) and reuptake (t1/2 33 vs. 61 s) were significantly reduced in AQP4(-/-) mice. ECS volume fraction measured by tetramethylammonium iontophoresis was greatly reduced during depolarizations from 0.18 to 0.053 in AQP4(+/+) mice, and 0.23 to 0.063 in AQP4(-/-) mice. Analysis of the experimental data using a mathematical model of CSD propagation suggested that the reduced velocity of CSD depolarizations in AQP4(-/-) mice was primarily a consequence of the slowed increase in [K(+)]e during neuronal depolarization. These results demonstrate that AQP4 effects on [K(+)]e and ECS volume dynamics accelerate CSD propagation.

Indexed as

Analysis of VarianceAnimalsAquaporin 4BrainCell FractionationCortical Spreading DepressionElectric StimulationExtracellular SpaceIon-Selective ElectrodesMiceMice, TransgenicModels, TheoreticalPotassiumAquaporin 4PotassiumAQP4astrocyteCSDextracellular spacepotassium

Identifiers

PMID25944186
PMCPMC4743984
OpenAlexW1490831218

What OpenQuestion holds

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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.