Evidence map›Paper›PMID 23977127›Full record

ArticlePloS one2013

Conformational changes in the lower palm domain of ASIC1a contribute to desensitization and RFamide modulation.

Erin N Frey, Ryan E Pavlovicz, Clem John Wegman, Chenglong Li, Candice C Askwith

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

16 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. 4-(Azolyl)-Benzamidines as a Novel Chemotype for ASIC1a Inhibitors.International journal of molecular sciences · 2024
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. ASICs and neuropeptides.Neuropharmacology · 2015
    Review
  14. Article
  15. Article
  16. Article
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 at 2 institutions in 1 country.

Erin N FreyDepartment of Neuroscience, Wexner Medical Center, The Ohio State University, Columbus, Ohio, United States of America ; Biomedical Sciences Graduate Program, The Ohio State University, Columbus, Ohio, United States of America.
Ryan E Pavlovicz
Clem John Wegman
Chenglong Li
Candice C Askwith
The Ohio State University Wexner Medical Center · USThe Ohio State University · US

Funding

Ohio State Neuroscience Centr CoreP30NS045758 · NINDS · OHIO STATE UNIVERSITY · PI MCTIGUE, DANA M · 2004 to 2015
$7.7M
Integrative Training in Biomedical SystemsT32GM068412 · NIGMS · OHIO STATE UNIVERSITY · PI PARVIN, JEFFREY D · 2005 to 2020
$2.4M
Neuropeptide Modulation of ASICsR01NS062967 · NINDS · OHIO STATE UNIVERSITY · PI ASKWITH, CANDICE C · 2008 to 2012
$1.3M
NIGMS NIH HHS T32 GM068412NINDS NIH HHS P30 NS045758NINDS NIH HHS R01 NS062967
6 · The paper itself

Abstract

Acid-sensing ion channel 1a (ASIC1a) is a proton-gated cation channel that contributes to fear and pain as well as neuronal damage following persistent cerebral acidosis. Neuropeptides can affect acid-induced neuronal injury by altering ASIC1a inactivation and/or steady-state desensitization. Yet, exactly how ASIC1a inactivation and desensitization occur or are modulated by peptides is not completely understood. We found that regions of the extracellular palm domain and the β(11-12) linker are important for inactivation and steady-state desensitization of ASIC1a. The single amino acid substitutions L280C and L415C dramatically enhanced the rate of inactivation and altered the pH-dependence of steady-state desensitization. Further, the use of methanethiosulfonate (MTS) reagents suggests that the lower palm region (L280C) undergoes a conformational change when ASIC1a transitions from closed to desensitized. We determined that L280C also displays an altered response to the RFamide peptide, FRRFamide. Further, the presence of FRRFamide limited MTS modification of L280C. Together, these results indicate a potential role of the lower palm domain in peptide modulation and suggest RFamide-related peptides promote conformational changes within this region. These data provide empirical support for the idea that L280, and likely this region of the central vestibule, is intimately involved in channel inactivation and desensitization.

Indexed as

Ion Channel GatingAcid Sensing Ion ChannelsAnimalsHumansMesylatesMutationNeuropeptidesProtein Structure, TertiaryStructure-Activity RelationshipXenopus laevisAcid Sensing Ion ChannelsASIC1 protein, humanMesylatesmethanethiosulfonateNeuropeptidesRFamide peptide

Identifiers

PMID23977127
PMCPMC3743763
OpenAlexW2074491222

What OpenQuestion holds

Textmetadata
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.