Evidence map›Paper›PMID 22411013›Full record

ArticleThe Journal of physiology2012

Neurons respond directly to mechanical deformation with pannexin-mediated ATP release and autostimulation of P2X7 receptors.

Jingsheng Xia, Jason C Lim, Wennan Lu, Jonathan M Beckel, Edward J Macarak, Alan M Laties, Claire H Mitchell

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

99 citing papers in PubMed, 155 citations in OpenAlex.

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  9. The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.International journal of molecular sciences · 2024
    Review
  10. Review
  11. Article
  12. Article
  13. Meningeal P2X7 Signaling Mediates Migraine-Related Intracranial Mechanical Hypersensitivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
  14. Article
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39 more citing papers are in PubMed but not listed here.

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 3 institutions in 2 countries.

Jingsheng XiaDepartment of Anatomy and Cell Biology, University of Pennsylvania, 440 Levy Building, 240 S. 40th St, Philadelphia, PA 19104, USA.
Jason C Lim
Wennan Lu
Jonathan M Beckel
Edward J Macarak
Alan M Laties
Claire H Mitchell
Institute of Cell Biology and Neurobiology · ITOphthalmology Associates (United States) · USUniversity of Pennsylvania · US

Funding

Scientific TransparencyP30EY001583 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CLAIRE H MITCHELL · 1985 to 2026
$19.5M
Transscleral Drug Delivery for Retinal DisordersR24EY017045 · NEI · EMORY UNIVERSITY · PI EDELHAUSER, HENRY FRANCIS · 2006 to 2010
$6.9M
Purines and the Health of Retinal Ganglion CellsR01EY015537 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, CLAIRE H · 2005 to 2023
$6.7M
REGULATION OF LYSOSOMAL PH IN RPE CELLSR01EY013434 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, CLAIRE H · 2002 to 2020
$5.3M
Disruption of Caldesmon Gene Expression in Bladder MyocytesR01DK069898 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI CHACKO, SAMUEL K. · 2005 to 2009
$1.8M
NEI NIH HHS EY001583NEI NIH HHS EY013434NEI NIH HHS EY015537NEI NIH HHS EY017045NEI NIH HHS P30 EY001583NEI NIH HHS R01 EY013434NEI NIH HHS R01 EY015537NEI NIH HHS R24 EY017045NIDDK NIH HHS DK069898NIDDK NIH HHS R01 DK069898
6 · The paper itself

Abstract

Mechanical deformation produces complex effects on neuronal systems, some of which can lead to dysfunction and neuronal death. While astrocytes are known to respond to mechanical forces, it is not clear whether neurons can also respond directly. We examined mechanosensitive ATP release and the physiological response to this release in isolated retinal ganglion cells. Purified ganglion cells released ATP upon swelling. Release was blocked by carbenoxolone, probenecid or peptide (10)panx, implicating pannexin channels as conduits. Mechanical stretch of retinal ganglion cells also triggered a pannexin-dependent ATP release. Whole cell patch clamp recording demonstrated that mild swelling induced the activation of an Ohmic cation current with linear kinetics. The current was inhibited by removal of extracellular ATP with apyrase, by inhibition of the P2X(7) receptor with A438079, zinc, or AZ 10606120, and by pannexin blockers carbenoxolone and probenecid. Probenecid also inhibited the regulatory volume decrease observed after swelling isolated neurons. Together, these observations indicate mechanical strain triggers ATP release directly from retinal ganglion cells and that this released ATP autostimulates P2X(7) receptors. Since extracellular ATP levels in the retina increase with elevated intraocular pressure, and stimulation of P2X(7) receptors on retinal ganglion cells can be lethal, this autocrine response may impact ganglion cells in glaucoma. It remains to be determined whether the autocrine stimulation of purinergic receptors is a general response to a mechanical deformation in neurons, or whether preventing ATP release through pannexin channels and blocking activation of the P2X(7) receptor, is neuroprotective for stretched neurons.

Indexed as

Adenosine TriphosphateAnimalsConnexinsNerve Tissue ProteinsRatsRats, Long-EvansReceptors, Purinergic P2X7Retinal Ganglion CellsStress, MechanicalAdenosine TriphosphateConnexinsNerve Tissue Proteinspannexin 1, ratReceptors, Purinergic P2X7

Identifiers

PMID22411013
PMCPMC3424753
OpenAlexW1514493016

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.