Evidence map›Paper›PMID 24643480›Full record

ArticlePflugers Archiv : European journal of physiology2014

Direct evidence for functional TRPV1/TRPA1 heteromers.

Michael J M Fischer, Dilshan Balasuriya, Pia Jeggle, Tom A Goetze, Peter A McNaughton, Peter W Reeh, J Michael Edwardson

Abstract read
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In one paragraph

Article in Pflugers Archiv : European journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
7.2field-weighted citation impact, top 2% 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

77 citing papers in PubMed, 119 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Correlation of TRPA1 RNAscope and Agonist Responses.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024
    Article
  9. Review
  10. The odyssey of the TR(i)P journey to the cellular membrane.Frontiers in cell and developmental biology · 2024
    Review
  11. Review
  12. Review
  13. Endogenous Derivatives of Linoleic Acid and their Stable Analogs Are Potential Pain Mediators.JID innovations : skin science from molecules to population health · 2023
    Article
  14. Nociception and pain in humans lacking a functional TRPV1 channel.The Journal of clinical investigation · 2023
    Article
  15. Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. Article

17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

Michael J M FischerInstitute of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Universitätsstrasse 17, 91052, Erlangen, Germany, fischer@physiologie1.uni-erlangen.de.
Dilshan Balasuriya
Pia Jeggle
Tom A Goetze
Peter A McNaughton
Peter W Reeh
J Michael Edwardson
University of Cambridge · GBFriedrich-Alexander-Universität Erlangen-Nürnberg · DEBridge University · SS

Funding

Biotechnology and Biological Sciences Research Council BB/C003217/1Biotechnology and Biological Sciences Research Council BB/F003072/1
6 · The paper itself

Abstract

Transient receptor potential cation channel, subfamily V, member 1 (TRPV1) plays a key role in sensing environmental hazards and in enhanced pain sensation following inflammation. A considerable proportion of TRPV1-expressing cells also express transient receptor potential cation channel, subfamily A, member 1 (TRPA1). There is evidence for a TRPV1-TRPA1 interaction that is predominantly calcium-dependent, and it has been suggested that the two proteins might form a heteromeric channel. Here, we constructed subunit concatemers to search for direct evidence for such an interaction. We found that a TRPV1::TRPV1 concatemer and TRPV1 formed channels with similar properties. A TRPV1::TRPA1 concatemer was responsive to TRPV1 agonists capsaicin, acidic pH and ethanol, but not to TRPA1 agonists. Isolated TRPV1 and TRPV1::TRPA1 imaged by atomic force microscopy (AFM) both had molecular volumes consistent with the formation of tetrameric channels. Antibodies decorated epitope tags on TRPV1 with a four-fold symmetry, as expected for a homotetramer. In contrast, pairs of antibodies decorated tags on TRPV1::TRPA1 predominantly at 180°, indicating the formation of a channel consisting of two TRPV1::TRPA1 concatemers arranged face to face. TRPV1::TRPA1 was sensitized by PKC activation and could be inhibited by a TRPV1 antagonist. TRPV1::TRPA1 was activated by heat and displayed a threshold and temperature coefficient similar to TRPV1. However, the channel formed by TRPV1::TRPA1 has only two binding sites for capsaicin and shows less total current and a smaller capsaicin-induced shift in voltage-dependent gating than TRPV1::TRPV1 or TRPV1. We conclude that the presence of TRPA1 exerts a functional inhibition on TRPV1.

Indexed as

Protein MultimerizationBinding SitesCalcium ChannelsCapsaicinHEK293 CellsHumansIon Channel GatingNerve Tissue ProteinsProtein BindingTransient Receptor Potential ChannelsTRPA1 Cation ChannelTRPV Cation ChannelsCalcium ChannelsCapsaicinNerve Tissue ProteinsTransient Receptor Potential ChannelsTRPA1 Cation ChannelTRPA1 protein, humanTRPV1 protein, humanTRPV Cation Channels

Identifiers

PMID24643480
OpenAlexW2052870492

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.