Evidence map›Paper›PMID 27169737›Full record

ArticleCirculation2016

Constitutive Intracellular Na+ Excess in Purkinje Cells Promotes Arrhythmogenesis at Lower Levels of Stress Than Ventricular Myocytes From Mice With Catecholaminergic Polymorphic Ventricular Tachycardia.

B Cicero Willis, Sandeep V Pandit, Daniela Ponce-Balbuena, Manuel Zarzoso, Guadalupe Guerrero-Serna, Bijay Limbu, Makarand Deo, Emmanuel Camors, Rafael J Ramirez, Sergey Mironov and 3 more

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In one paragraph

Article in Circulation, 2016. 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

3.4field-weighted citation impact, top 7% 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, 30 citations in OpenAlex.

Management of patients with an electrical storm or clustered ventricular arrhythmias: a clinical consensus statement of the European Heart Rhythm Association of the ESC-endorsed by the Asia-Pacific Heart Rhythm Society, Heart Rhythm Society, and Latin-American Heart Rhythm Society.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 · 2024
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Kir2.1 dysfunction at the sarcolemma and the sarcoplasmic reticulum causes arrhythmias in a mouse model of Andersen-Tawil syndrome type 1.Nature cardiovascular research · 2022
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SNTA1-deficient human cardiomyocytes demonstrate hypertrophic phenotype and calcium handling disorder.Stem cell research & therapy · 2022
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Cardiomyocyte NaBasic research in cardiology · 2021
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Genetic Loss ofCirculation. Arrhythmia and electrophysiology · 2020
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A Recurrent Exertional Syncope and Sudden Cardiac Arrest in a Young Athlete with Known Pathogenic p.Arg420Gln Variant in theDiagnostics (Basel, Switzerland) · 2020
Article
Delayed afterdepolarization-induced triggered activity in cardiac purkinje cells mediated through cytosolic calcium diffusion waves.Physiological reports · 2019
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Phosphorylation of the ryanodine receptor 2 at serine 2030 is required for a complete β-adrenergic response.The Journal of general physiology · 2019
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CPVT: Arrhythmogenesis, Therapeutic Management, and Future Perspectives. A Brief Review of the Literature.Frontiers in cardiovascular medicine · 2019
Review
The transient receptor potential melastatin 4 channel inhibitor 9-phenanthrol modulates cardiac sodium channel.British journal of pharmacology · 2018
Article
Ventricular arrhythmias involving the His-Purkinje system in the structurally abnormal heart.Pacing and clinical electrophysiology : PACE · 2018
Review
Purkinje physiology and pathophysiology.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2018
Review
Role of genetic and electrolyte abnormalities in prolonged QTc interval and sudden cardiac death in end-stage renal disease patients.PloS one · 2018
Article
Synergistic Research Between the Center of Arrhythmia Research and the Michigan Biology of Cardiovascular Aging at the University of Michigan.Circulation research · 2017
Article
Targeted next-generation sequencing provides novel clues for associated epilepsy and cardiac conduction disorder/SUDEP.PloS one · 2017
Article
Cardiac electrical defects in progeroid mice and Hutchinson-Gilford progeria syndrome patients with nuclear lamina alterations.Proceedings of the National Academy of Sciences of the United States of America · 2016
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

13 authors at 2 institutions in 1 country.

B Cicero WillisFrom University of Michigan, Ann Arbor (B.C.W., S.V.P., D.P.-B., M.Z., G.G.-S., R.J.R., S.M., T.J.H., H.H.V., J.J.); Norfolk State University, VA (B.L., M.D.); University of Tennessee Health Science Center, Memphis (E.C.); and Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (J.J.).

Sandeep V PanditFrom University of Michigan, Ann Arbor (B.C.W., S.V.P., D.P.-B., M.Z., G.G.-S., R.J.R., S.M., T.J.H., H.H.V., J.J.); Norfolk State University, VA (B.L., M.D.); University of Tennessee Health Science Center, Memphis (E.C.); and Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (J.J.).

Daniela Ponce-BalbuenaFrom University of Michigan, Ann Arbor (B.C.W., S.V.P., D.P.-B., M.Z., G.G.-S., R.J.R., S.M., T.J.H., H.H.V., J.J.); Norfolk State University, VA (B.L., M.D.); University of Tennessee Health Science Center, Memphis (E.C.); and Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (J.J.).

Manuel ZarzosoFrom University of Michigan, Ann Arbor (B.C.W., S.V.P., D.P.-B., M.Z., G.G.-S., R.J.R., S.M., T.J.H., H.H.V., J.J.); Norfolk State University, VA (B.L., M.D.); University of Tennessee Health Science Center, Memphis (E.C.); and Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (J.J.).

Guadalupe Guerrero-SernaFrom University of Michigan, Ann Arbor (B.C.W., S.V.P., D.P.-B., M.Z., G.G.-S., R.J.R., S.M., T.J.H., H.H.V., J.J.); Norfolk State University, VA (B.L., M.D.); University of Tennessee Health Science Center, Memphis (E.C.); and Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (J.J.).

Bijay LimbuFrom University of Michigan, Ann Arbor (B.C.W., S.V.P., D.P.-B., M.Z., G.G.-S., R.J.R., S.M., T.J.H., H.H.V., J.J.); Norfolk State University, VA (B.L., M.D.); University of Tennessee Health Science Center, Memphis (E.C.); and Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (J.J.).

Makarand DeoFrom University of Michigan, Ann Arbor (B.C.W., S.V.P., D.P.-B., M.Z., G.G.-S., R.J.R., S.M., T.J.H., H.H.V., J.J.); Norfolk State University, VA (B.L., M.D.); University of Tennessee Health Science Center, Memphis (E.C.); and Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (J.J.).

Emmanuel CamorsFrom University of Michigan, Ann Arbor (B.C.W., S.V.P., D.P.-B., M.Z., G.G.-S., R.J.R., S.M., T.J.H., H.H.V., J.J.); Norfolk State University, VA (B.L., M.D.); University of Tennessee Health Science Center, Memphis (E.C.); and Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (J.J.).

Rafael J RamirezFrom University of Michigan, Ann Arbor (B.C.W., S.V.P., D.P.-B., M.Z., G.G.-S., R.J.R., S.M., T.J.H., H.H.V., J.J.); Norfolk State University, VA (B.L., M.D.); University of Tennessee Health Science Center, Memphis (E.C.); and Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (J.J.).

Sergey MironovFrom University of Michigan, Ann Arbor (B.C.W., S.V.P., D.P.-B., M.Z., G.G.-S., R.J.R., S.M., T.J.H., H.H.V., J.J.); Norfolk State University, VA (B.L., M.D.); University of Tennessee Health Science Center, Memphis (E.C.); and Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (J.J.).

Todd J HerronFrom University of Michigan, Ann Arbor (B.C.W., S.V.P., D.P.-B., M.Z., G.G.-S., R.J.R., S.M., T.J.H., H.H.V., J.J.); Norfolk State University, VA (B.L., M.D.); University of Tennessee Health Science Center, Memphis (E.C.); and Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (J.J.).

Héctor H ValdiviaFrom University of Michigan, Ann Arbor (B.C.W., S.V.P., D.P.-B., M.Z., G.G.-S., R.J.R., S.M., T.J.H., H.H.V., J.J.); Norfolk State University, VA (B.L., M.D.); University of Tennessee Health Science Center, Memphis (E.C.); and Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (J.J.).

José JalifeFrom University of Michigan, Ann Arbor (B.C.W., S.V.P., D.P.-B., M.Z., G.G.-S., R.J.R., S.M., T.J.H., H.H.V., J.J.); Norfolk State University, VA (B.L., M.D.); University of Tennessee Health Science Center, Memphis (E.C.); and Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (J.J.). jjalife@umich.edu.

Norfolk State University · USUniversity of Tennessee Health Science Center · US

Funding

THREE DIMENSIONAL VORTEX LIKE REENTRY IN CORONARY PERFUSED VENTRICULAR WALLP01HL039707 · NHLBI · UPSTATE MEDICAL UNIVERSITY · PI ZAITSEV, ALEXEY V · 1990 to 2010

$19.0M

P3: Biophysical Mechanisms in two Arhythmogenic DiseasesP01HL087226 · NHLBI · UPSTATE MEDICAL UNIVERSITY · PI JALIFE, JOSE S · 2007 to 2012

$10.3M

Ryanodine Receptors, Calcium-dependent Arrhythmias & HCMR01HL055438 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI VALDIVIA, HECTOR H · 1996 to 2023

$8.0M

Intermolecular Interactions of NaV1.5 and Kir2.1 In Ion Channel DiseasesR01HL122352 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BERENFELD, OMER · 2015 to 2018

$1.9M

Cytosolic Calcium Sweeper in Cardiac MyocytesR01HL120108 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI VALDIVIA, HECTOR H · 2014 to 2017

$1.5M

American Heart Association-American Stroke Association 12SDG11480010NHLBI NIH HHS P01 HL039707NHLBI NIH HHS P01 HL087226NHLBI NIH HHS R01 HL055438NHLBI NIH HHS R01 HL120108NHLBI NIH HHS R01 HL122352

6 · The paper itself

Abstract

backgroundIn catecholaminergic polymorphic ventricular tachycardia (CPVT), cardiac Purkinje cells (PCs) appear more susceptible to Ca(2+) dysfunction than ventricular myocytes (VMs). The underlying mechanisms remain unknown. Using a CPVT mouse (RyR2(R4496C+/Cx40eGFP)), we tested whether PC intracellular Ca(2+) ([Ca(2+)]i) dysregulation results from a constitutive [Na(+)]i surplus relative to VMs. METHODS AND

resultsSimultaneous optical mapping of voltage and [Ca(2+)]i in CPVT hearts showed that spontaneous Ca(2+) release preceded pacing-induced triggered activity at subendocardial PCs. On simultaneous current-clamp and Ca(2+) imaging, early and delayed afterdepolarizations trailed spontaneous Ca(2+) release and were more frequent in CPVT PCs than CPVT VMs. As a result of increased activity of mutant ryanodine receptor type 2 channels, sarcoplasmic reticulum Ca(2+) load, measured by caffeine-induced Ca(2+) transients, was lower in CPVT VMs and PCs than respective controls, and sarcoplasmic reticulum fractional release was greater in both CPVT PCs and VMs than respective controls. [Na(+)]i was higher in both control and CPVT PCs than VMs, whereas the density of the Na(+)/Ca(2+) exchanger current was not different between PCs and VMs. Computer simulations using a PC model predicted that the elevated [Na(+)]i of PCs promoted delayed afterdepolarizations, which were always preceded by spontaneous Ca(2+) release events from hyperactive ryanodine receptor type 2 channels. Increasing [Na(+)]i monotonically increased delayed afterdepolarization frequency. Confocal imaging experiments showed that postpacing Ca(2+) spark frequency was highest in intact CPVT PCs, but such differences were reversed on saponin-induced membrane permeabilization, indicating that differences in [Na(+)]i played a central role.

conclusionsIn CPVT mice, the constitutive [Na(+)]i excess of PCs promotes triggered activity and arrhythmogenesis at lower levels of stress than VMs.

Indexed as

AnimalsCalciumCalcium SignalingHumansMiceMyocytes, CardiacPolymorphic Catecholaminergic Ventricular TachycardiaPurkinje CellsSodiumTachycardia, VentricularCalciumSodiumarrhythmias, cardiaccalciumcalcium signalingsodium-calcium exchanger

Identifiers

PMID27169737

DOI10.1161/CIRCULATIONAHA.116.021936

PMCPMC4902321

OpenAlexW2383241784

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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.