Evidence map›Paper›PMID 25568328›Full record

ArticleThe Journal of biological chemistry2015

Role of the outer pore domain in transient receptor potential vanilloid 1 dynamic permeability to large cations.

Clare H Munns, Man-Kyo Chung, Yuly E Sanchez, L Mario Amzel, Michael J Caterina

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
–field-weighted citation impact
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

29 citing papers in PubMed.

  1. Dilation of ion selectivity filters in cation channels.Trends in biochemical sciences · 2024
    Review
  2. Blockade of TRPV channels by intracellular spermine.The Journal of general physiology · 2023
    Article
  3. Genetically-encoded BRET probes shed light on ligand bias-induced variable ion selectivity in TRPV1 and P2X5/7.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Channels (Austin, Tex.) · 2019
    Article
  12. Review
  13. Article
  14. Article
  15. 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

5 authors.

Clare H MunnsFrom the Departments of Neurosurgery, Biological Chemistry, and Neuroscience, Neurosurgery Pain Research Institute, and Center for Sensory Biology and.
Man-Kyo Chungthe Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, Maryland 21201.
Yuly E SanchezDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, the Departamento de Física, Facultad de Ciencias, Universidad Nacional de Colombia, 111321 Bogotá, D.C., Colombia, and the Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, 110231 Bogotá, D.C., Colombia.
L Mario AmzelDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
Michael J CaterinaFrom the Departments of Neurosurgery, Biological Chemistry, and Neuroscience, Neurosurgery Pain Research Institute, and Center for Sensory Biology and caterina@jhmi.edu.

Funding

Genetic and post-translational modifications of TRPV1 in craniofacial painR01DE023846 · NIDCR · UNIVERSITY OF MARYLAND BALTIMORE · PI CHUNG, MAN-KYO · 2014 to 2018
$1.9M
Agonist-evoked changes in TRPV ion channel selectivityR01NS054902 · NINDS · JOHNS HOPKINS UNIVERSITY · PI CATERINA, MICHAEL J · 2007 to 2011
$1.2M
NIDCR NIH HHS DE023846NIDCR NIH HHS R01 DE023846NINDS NIH HHS NS054902NINDS NIH HHS R01 NS054902
6 · The paper itself

Abstract

Transient receptor potential vanilloid 1 (TRPV1) has been shown to alter its ionic selectivity profile in a time- and agonist-dependent manner. One hallmark of this dynamic process is an increased permeability to large cations such as N-methyl-D-glucamine (NMDG). In this study, we mutated residues throughout the TRPV1 pore domain to identify loci that contribute to dynamic large cation permeability. Using resiniferatoxin (RTX) as the agonist, we identified multiple gain-of-function substitutions within the TRPV1 pore turret (N628P and S629A), pore helix (F638A), and selectivity filter (M644A) domains. In all of these mutants, maximum NMDG permeability was substantially greater than that recorded in wild type TRPV1, despite similar or even reduced sodium current density. Two additional mutants, located in the pore turret (G618W) and selectivity filter (M644I), resulted in significantly reduced maximum NMDG permeability. M644A and M644I also showed increased and decreased minimum NMDG permeability, respectively. The phenotypes of this panel of mutants were confirmed by imaging the RTX-evoked uptake of the large cationic fluorescent dye YO-PRO1. Whereas none of the mutations selectively altered capsaicin-induced changes in NMDG permeability, the loss-of-function phenotypes seen with RTX stimulation of G618W and M644I were recapitulated in the capsaicin-evoked YO-PRO1 uptake assay. Curiously, the M644A substitution resulted in a loss, rather than a gain, in capsaicin-evoked YO-PRO1 uptake. Modeling of our mutations onto the recently determined TRPV1 structure revealed several plausible mechanisms for the phenotypes observed. We conclude that side chain interactions at a few specific loci within the TRPV1 pore contribute to the dynamic process of ionic selectivity.

Indexed as

Protein Structure, SecondaryProtein Structure, TertiaryAnimalsBenzoxazolesBiological TransportCapsaicinCationsDiterpenesFluorescent DyesHEK293 CellsHumansIon Channel GatingMeglumineMiceModels, MolecularMutation, MissenseBenzoxazolesCapsaicinCationsDiterpenesFluorescent DyesMeglumineQuinolinium CompoundsresiniferatoxinTRPV1 protein, mouseTrpv1 protein, ratTRPV Cation ChannelsYO-PRO 1CapsaicinImagingN-Methyl-D-glucaminePatch ClampPermeabilityPoreResiniferatoxinSite-directed MutagenesisTransient Receptor Potential Channels (TRP Channels)TRPV1

Identifiers

PMID25568328
PMCPMC4342482

What OpenQuestion holds

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Registered trials

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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.