Evidence map›Paper›PMID 34676560›Full record

ArticleThe Journal of physiology2021

The V2475F CPVT1 mutation yields distinct RyR2 channel populations that differ in their responses to cytosolic Ca

Abigail D Wilson, Jianshu Hu, Charalampos Sigalas, Elisa Venturi, Héctor H Valdivia, Carmen R Valdivia, Ming Lei, Maria Musgaard, Rebecca Sitsapesan

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. 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

9 authors at 3 institutions in 3 countries.

Abigail D WilsonDepartment of Pharmacology, University of Oxford, Oxford, UK.ORCID 0000-0002-9786-3405
Jianshu HuDepartment of Pharmacology, University of Oxford, Oxford, UK.ORCID 0000-0003-1384-7465
Charalampos SigalasDepartment of Pharmacology, University of Oxford, Oxford, UK.ORCID 0000-0003-0405-1385
Elisa VenturiDepartment of Pharmacology, University of Oxford, Oxford, UK.ORCID 0000-0001-9302-1537
Héctor H ValdiviaDepartment of Medicine, Division of Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, Madison, USA.ORCID 0000-0003-1231-6267
Carmen R ValdiviaDepartment of Medicine, Division of Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, Madison, USA.
Ming LeiDepartment of Pharmacology, University of Oxford, Oxford, UK.ORCID 0000-0002-0928-341X
Maria MusgaardDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.ORCID 0000-0001-6096-9014
Rebecca SitsapesanDepartment of Pharmacology, University of Oxford, Oxford, UK.ORCID 0000-0002-3216-2560
University of Oxford · GBUniversity of Wisconsin–Madison · USUniversity of Ottawa · CA

Funding

Ryanodine Receptors, Calcium-dependent Arrhythmias & HCMR01HL055438 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI VALDIVIA, HECTOR H · 1996 to 2023
$8.0M
Natural Agonists of Ryanodine Receptors: Structure-function Relationship and Antiarrhythmic PropertiesR01HL134344 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI VALDIVIA, HECTOR H · 2017 to 2020
$1.9M
British Heart Foundation FS/16/59/32735British Heart Foundation PG/19/38/34403British Heart Foundation PG/19/67/34607NHLBI NIH HHS R01 HL055438NHLBI NIH HHS R01 HL134344
6 · The paper itself

Abstract

Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is a lethal genetic disease causing arrhythmias and sudden cardiac death in children and young adults and is linked to mutations in the cardiac ryanodine receptor (RyR2). The effects of CPVT1 mutations on RyR2 ion-channel function are often investigated using purified recombinant RyR2 channels homozygous for the mutation. However, CPVT1 patients are heterozygous for the disease, so this approach does not reveal the true changes to RyR2 function across the entire RyR2 population of channels in the heart. We therefore investigated the native cardiac RyR2 single-channel abnormalities in mice heterozygous for the CPVT1 mutation, V2475F(+/-)-RyR2, and applied molecular modelling techniques to investigate the possible structural changes that could initiate any altered function. We observed that increased sensitivity of cardiac V2475F(+/-)-RyR2 channels to both activating and inactivating levels of cytosolic Ca

Indexed as

Ryanodine Receptor Calcium Release ChannelTachycardia, VentricularAnimalsCalciumCalcium SignalingHumansMiceMutationSarcoplasmic ReticulumCalciumRyanodine Receptor Calcium Release Channelcatecholaminergic polymorphic ventricular tachycardiaRyR2sarcoplasmic reticulum Ca2+ releasesingle channel

Identifiers

PMID34676560
PMCPMC8996374
OpenAlexW3206568769

What OpenQuestion holds

Textmetadata
LicenceTDM
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.