Evidence map›Paper›PMID 36102198›Full record

ArticleCirculation research2022

Impaired Dynamic Sarcoplasmic Reticulum Ca Buffering in Autosomal Dominant CPVT2.

Matthew J Wleklinski, Dmytro O Kryshtal, Kyungsoo Kim, Shan S Parikh, Daniel J Blackwell, Isabelle Marty, V Ramesh Iyer, Bjӧrn C Knollmann

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Ca2+ signalling in cardiac muscle: the importance of balances.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026
    Review
  3. Article
  4. Review
  5. Gene Therapy for Inherited Cardiac Arrhythmias.Journal of cardiovascular translational research · 2025
    Review
  6. Article
  7. Review
  8. Human Genetics of Cardiac Arrhythmias.Advances in experimental medicine and biology · 2024
    Review
  9. Review
  10. Article
  11. 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

8 authors at 3 institutions in 2 countries.

Matthew J WleklinskiVanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN (M.J.W., D.O.K., K.K., S.S.P., D.J.B., B.C.K.).ORCID 0000-0002-1198-2834
Dmytro O KryshtalVanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN (M.J.W., D.O.K., K.K., S.S.P., D.J.B., B.C.K.).ORCID 0000-0002-0427-6587
Kyungsoo KimVanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN (M.J.W., D.O.K., K.K., S.S.P., D.J.B., B.C.K.).ORCID 0000-0003-2869-0659
Shan S ParikhVanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN (M.J.W., D.O.K., K.K., S.S.P., D.J.B., B.C.K.).
Daniel J BlackwellVanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN (M.J.W., D.O.K., K.K., S.S.P., D.J.B., B.C.K.).ORCID 0000-0001-6619-1792
Isabelle MartyUniversity Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences, Grenoble, France (I.M.).
V Ramesh IyerDivision of Cardiology, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania (V.R.I.).
Bjӧrn C KnollmannVanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN (M.J.W., D.O.K., K.K., S.S.P., D.J.B., B.C.K.).ORCID 0000-0003-4956-9735
Vanderbilt University Medical Center · USChildren's Hospital of Philadelphia · USInserm · FR

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ALVIN C POWERS · 2012 to 2026
$29.3M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007347 · NIGMS · VANDERBILT UNIVERSITY · PI WILLIAMS, CHRISTOPHER S. · 1985 to 2023
$26.3M
Shop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI David J. Calkins · 1989 to 2026
$19.6M
Vanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9M
Toward a Mechanism-Based Approach to Treating Cardiac ArrhythmiaR35HL144980 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI KNOLLMANN, BJORN C · 2019 to 2025
$7.1M
Medical Scientist Training ProgramT32GM152284 · NIGMS · VANDERBILT UNIVERSITY · PI Christopher S. Williams · 2024 to 2026
$4.8M
Cardiac Calsequestrin (Casq2) function in excitation-contraction coupling and cardiac arrhythmiasF30HL145917 · NHLBI · VANDERBILT UNIVERSITY · PI WLEKLINSKI, MATTHEW J · 2019 to 2022
$160k
NCI NIH HHS P30 CA068485NEI NIH HHS P30 EY008126NHLBI NIH HHS F30 HL145917NHLBI NIH HHS R35 HL144980NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK058404NIDDK NIH HHS U24 DK059637NIGMS NIH HHS T32 GM007347NIGMS NIH HHS T32 GM152284
6 · The paper itself

Abstract

backgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal cardiac arrhythmia syndrome triggered by catecholamines released during exercise, stress, or sudden emotion. Variants in the calsequestrin-2 gene (

methodsA K180R mouse model was generated using CRIPSR/Cas9. Heterozygous and homozygous K180R mice were studied using telemetry ECG recordings in vivo. Ventricular cardiomyocytes were isolated and studied using fluorescent Ca indicators and patch clamp. Expression levels and localization of SR Ca-handling proteins were evaluated using Western blotting and immunostaining. Intra-SR Ca kinetics were quantified using low-affinity Ca indicators.

resultsK180R mice exhibit an autosomal dominant CPVT phenotype following exercise or catecholamine stress. Upon catecholamine stress, K180R ventricular cardiomyocytes exhibit increased spontaneous SR Ca release events, triggering delayed afterdepolarizations and spontaneous beats. K180R had no effect on levels of Casq2, Casq2 polymers, or other SR Ca-handling proteins. Intra-SR Ca measurements revealed that K180R impaired dynamic intra-SR Ca buffering, resulting in a more rapid rise of free Ca in the SR during diastole. Steady-state SR Ca buffering and total SR Ca content were not changed. Consistent with the reduced dynamic intra-SR buffering, K180R causes reduced SR Ca release refractoriness.

conclusions

Indexed as

Sarcoplasmic ReticulumTachycardia, VentricularAnimalsCalciumCalcium-Binding ProteinsCalsequestrinCatecholaminesMiceMyocytes, CardiacPolymersPolymorphic Catecholaminergic Ventricular TachycardiaRyanodine Receptor Calcium Release ChannelCalciumCalcium-Binding ProteinsCalsequestrinCatecholaminesPolymersRyanodine Receptor Calcium Release Channelcalciumcalsequestrincatecholaminesarcoplasmic reticulumtachycardia

Identifiers

PMID36102198
PMCPMC9529867
OpenAlexW4295575614

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.