Evidence map›Paper›PMID 25918358›Full record

ArticleThe Journal of general physiology2015

Targeting the late component of the cardiac L-type Ca2+ current to suppress early afterdepolarizations.

Roshni V Madhvani, Marina Angelini, Yuanfang Xie, Antonios Pantazis, Silvie Suriany, Nils P Borgstrom, Alan Garfinkel, Zhilin Qu, James N Weiss, Riccardo Olcese

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

Article in The Journal of general physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

38 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
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  10. Review
  11. Zingerone Modulates Neuronal Voltage-Gated NaInternational journal of molecular sciences · 2022
    Article
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  14. Prediction of arrhythmia susceptibility through mathematical modeling and machine learning.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  15. Article
  16. Genetic and Molecular Aspects of Drug-Induced QT Interval Prolongation.International journal of molecular sciences · 2021
    Review
  17. Article
  18. Article
  19. Article
  20. R-From-T as a Common Mechanism of Arrhythmia Initiation in Long QT Syndromes.Circulation. Arrhythmia and electrophysiology · 2019
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Roshni V MadhvaniDivision of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095.
Marina AngeliniDivision of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095.
Yuanfang XieDepartment of Pharmacology, University of California, Davis, Davis, CA 95616.
Antonios PantazisDivision of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095.
Silvie SurianyDivision of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095.
Nils P BorgstromDivision of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095.
Alan GarfinkelDivision of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095 Division of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095 Division of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095.
Zhilin QuDivision of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095 Division of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095.
James N WeissDivision of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095 Division of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095 Division of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095.
Riccardo OlceseDivision of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095 Division of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095 Division of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095 Division of Molecular Medicine, Department of Anesthesiology, Department of Medicine (Cardiology), Department of Physiology, Department of Integrative Biology and Physiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095 rolcese@ucla.edu.
Cardiovascular Research Center · BRLaboratoire d’immunologie intégrative du cancer · FRUniversity of California, Los Angeles · USUniversity of California, Davis · US

Funding

WAVE DYNAMICS IN NORMAL AND DISEASED RABBIT HEARTSP01HL078931 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WEISS, JAMES · 2005 to 2015
$20.7M
Structural Changes in BKCa Channels During GatingR01GM082289 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI OLCESE, RICCARDO · 2008 to 2011
$1.4M
Afterdepolarizations and Cardiac ArrhythmiasR01HL103662 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WEISS, JAMES N · 2010 to 2010
$407k
NHLBI NIH HHS P01 HL078931NHLBI NIH HHS P01HL78931NHLBI NIH HHS R01 HL103662NIGMS NIH HHS R01 GM082289NIGMS NIH HHS R01GM082289
6 · The paper itself

Abstract

Early afterdepolarizations (EADs) associated with prolongation of the cardiac action potential (AP) can create heterogeneity of repolarization and premature extrasystoles, triggering focal and reentrant arrhythmias. Because the L-type Ca(2+) current (ICa,L) plays a key role in both AP prolongation and EAD formation, L-type Ca(2+) channels (LTCCs) represent a promising therapeutic target to normalize AP duration (APD) and suppress EADs and their arrhythmogenic consequences. We used the dynamic-clamp technique to systematically explore how the biophysical properties of LTCCs could be modified to normalize APD and suppress EADs without impairing excitation-contraction coupling. Isolated rabbit ventricular myocytes were first exposed to H2O2 or moderate hypokalemia to induce EADs, after which their endogenous ICa,L was replaced by a virtual ICa,L with tunable parameters, in dynamic-clamp mode. We probed the sensitivity of EADs to changes in the (a) amplitude of the noninactivating pedestal current; (b) slope of voltage-dependent activation; (c) slope of voltage-dependent inactivation; (d) time constant of voltage-dependent activation; and (e) time constant of voltage-dependent inactivation. We found that reducing the amplitude of the noninactivating pedestal component of ICa,L effectively suppressed both H2O2- and hypokalemia-induced EADs and restored APD. These results, together with our previous work, demonstrate the potential of this hybrid experimental-computational approach to guide drug discovery or gene therapy strategies by identifying and targeting selective properties of LTCC.

Indexed as

Action PotentialsAnimalsCalcium Channels, L-TypeCells, CulturedHeart VentriclesMaleMembrane PotentialsMyocytes, CardiacRabbitsCalcium Channels, L-Type

Identifiers

PMID25918358
PMCPMC4411259
OpenAlexW2145384798

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.