Evidence map›Paper›PMID 26489684›Full record

ArticleASN neuro

Osmotic Edema Rapidly Increases Neuronal Excitability Through Activation of NMDA Receptor-Dependent Slow Inward Currents in Juvenile and Adult Hippocampus.

Kelli Lauderdale, Thomas Murphy, Tina Tung, David Davila, Devin K Binder, Todd A Fiacco

Open access · goldAbstract read
In one paragraph

Article in ASN neuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

36 citing papers in PubMed, 52 citations in OpenAlex.

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  6. Five percent CONeuroprotection (Chichester, England) · 2024
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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 1 institution in 1 country.

Kelli LauderdaleDepartment of Cell Biology and Neuroscience, Riverside, CA, USA Center for Glial-Neuronal Interactions, University of California Riverside, CA, USA.
Thomas MurphyDepartment of Cell Biology and Neuroscience, Riverside, CA, USA Center for Glial-Neuronal Interactions, University of California Riverside, CA, USA.
Tina TungDepartment of Cell Biology and Neuroscience, Riverside, CA, USA.
David DavilaDepartment of Cell Biology and Neuroscience, Riverside, CA, USA.
Devin K BinderCenter for Glial-Neuronal Interactions, University of California Riverside, CA, USA Division of Biomedical Sciences, UC Riverside School of Medicine, CA, USA.
Todd A FiaccoDepartment of Cell Biology and Neuroscience, Riverside, CA, USA Center for Glial-Neuronal Interactions, University of California Riverside, CA, USA toddf@ucr.edu.
University of California, Riverside · US

Funding

Astrocyte volume-regulated control of neuronal excitabilityR01NS082570 · NINDS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI BINDER, DEVIN K, FIACCO, TODD A · 2013 to 2017
$1.7M
NINDS NIH HHS R01 NS082570NINDS NIH HHS R01NS082570
6 · The paper itself

Abstract

Cellular edema (cell swelling) is a principal component of numerous brain disorders including ischemia, cortical spreading depression, hyponatremia, and epilepsy. Cellular edema increases seizure-like activity in vitro and in vivo, largely through nonsynaptic mechanisms attributable to reduction of the extracellular space. However, the types of excitability changes occurring in individual neurons during the acute phase of cell volume increase remain unclear. Using whole-cell patch clamp techniques, we report that one of the first effects of osmotic edema on excitability of CA1 pyramidal cells is the generation of slow inward currents (SICs), which initiate after approximately 1 min. Frequency of SICs increased as osmolarity decreased in a dose-dependent manner. Imaging of real-time volume changes in astrocytes revealed that neuronal SICs occurred while astrocytes were still in the process of swelling. SICs evoked by cell swelling were mainly nonsynaptic in origin and NMDA receptor-dependent. To better understand the relationship between SICs and changes in neuronal excitability, recordings were performed in increasingly physiological conditions. In the absence of any added pharmacological reagents or imposed voltage clamp, osmotic edema induced excitatory postsynaptic potentials and burst firing over the same timecourse as SICs. Like SICs, action potentials were blocked by NMDAR antagonists. Effects were more pronounced in adult (8-20 weeks old) compared with juvenile (P15-P21) mice. Together, our results indicate that cell swelling triggered by reduced osmolarity rapidly increases neuronal excitability through activation of NMDA receptors. Our findings have important implications for understanding nonsynaptic mechanisms of epilepsy in relation to cell swelling and reduction of the extracellular space.

Indexed as

AgingAnimalsAstrocytesBrain EdemaCA1 Region, HippocampalCations, DivalentCell SizeMagnesiumMaleMembrane PotentialsMice, Inbred C57BLOsmolar ConcentrationPatch-Clamp TechniquesPyramidal CellsReceptors, N-Methyl-D-AspartateTissue Culture TechniquesCations, DivalentMagnesiumReceptors, N-Methyl-D-Aspartateaction potentialbursting activityCA1 pyramidal neuroncell swellingepilepsyextracellular spaceextrasynapticglutamatehypoosmolarNMDA receptorseizureslow inward currentvolume regulated anion channel

Identifiers

PMID26489684
PMCPMC4623564
OpenAlexW2289528536

What OpenQuestion holds

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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.