ArticleStem cell reports2014
Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia.
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Article in Stem cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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65citing papers in PubMed
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65 citing papers in PubMed, 118 citations in OpenAlex.
- Gradient-based parameter optimization method to determine membrane ionic current composition in human induced pluripotent stem cell-derived cardiomyocytes.Scientific reports · 2022Trial
- Modeling ventricular tachycardia in genetic long QT syndrome using engineered cardiac tissues.Bioactive materials · 2026Article
- A humanized engineered heart tissue platform for cardiotoxicity assessment.Stem cell reports · 2026Article
- The Role of Loss-of-Function KCNH2 Variants in Cardiac Arrhythmias, Seizures and the Risk of Sudden Unexpected Death in Epilepsy.Journal of neurochemistry · 2026Review
- Atrial arrhythmogenesis and electrophysiological remodeling in hypokalaemic metabolic syndrome: the role of apamin-sensitive SK channels.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 · 2025Article
- Pathogenic KCNH2-G53S variant in the PAS domain influences the electrophysiological phenotype in long QT syndrome type 2.Frontiers in cardiovascular medicine · 2025Article
- Using a Failing Human Ventricular Cardiomyocyte Model to Re-Evaluate CaBiomolecules · 2024Article
- Human multilineage pro-epicardium/foregut organoids support the development of an epicardium/myocardium organoid.Nature communications · 2022Article
- Optogenetic Reporters Delivered as mRNA Facilitate Repeatable Action Potential and Calcium Handling Assessment in Human iPSC-Derived Cardiomyocytes.Stem cells (Dayton, Ohio) · 2022Article
- Deriving waveform parameters from calcium transients in human iPSC-derived cardiomyocytes to predict cardiac activity with machine learning.Stem cell reports · 2022Article
- Qiliqiangxin Capsule Modulates Calcium Transients and Calcium Sparks in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Deciphering Common Long QT Syndrome Using CRISPR/Cas9 in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Frontiers in cardiovascular medicine · 2022Review
- Identifying Acute Cardiac Hazard in Early Drug Discovery Using a Calcium Transient High-Throughput Assay in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Frontiers in physiology · 2022Article
- Modeling theeLife · 2021Article
- Cardiomyocyte NaBasic research in cardiology · 2021Article
- Machine Learning Techniques to Classify Healthy and Diseased Cardiomyocytes by Contractility Profile.ACS biomaterials science & engineering · 2021Article
- Mechanisms of phase-3 early afterdepolarizations and triggered activities in ventricular myocyte models.Physiological reports · 2021Article
- Patient-specific induced pluripotent stem cells as "disease-in-a-dish" models for inherited cardiomyopathies and channelopathies - 15 years of research.World journal of stem cells · 2021Review
- Article
- Modeling Human TBX5 Haploinsufficiency Predicts Regulatory Networks for Congenital Heart Disease.Developmental cell · 2021Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 5 institutions in 3 countries.
C Ian SpencerGladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA.
Shiro BabaGladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA; Departments of Medicine, Anatomy and Cellular and Molecular Pharmacology, University of California San Francisco, 500 Parnassus Avenue, San Francisco, CA 94143, USA.
Kenta NakamuraGladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA; Departments of Medicine, Anatomy and Cellular and Molecular Pharmacology, University of California San Francisco, 500 Parnassus Avenue, San Francisco, CA 94143, USA.
Ethan A HuaGladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA.
Marie A F SearsGladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA.
Chi-cheng FuGladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA; Departments of Bioengineering, and Material Science and Engineering, University of California, Berkeley, CA 94720, USA.
Jianhua ZhangStem Cell and Regenerative Medicine Center, Cellular and Molecular Arrhythmia Research Program, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, Madison, WI 53792, USA.
Sadguna BalijepalliStem Cell and Regenerative Medicine Center, Cellular and Molecular Arrhythmia Research Program, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, Madison, WI 53792, USA.
Kiichiro TomodaGladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA.
Yohei HayashiGladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA.
Paweena LizarragaGladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA.
Julianne WojciakDepartments of Medicine, Anatomy and Cellular and Molecular Pharmacology, University of California San Francisco, 500 Parnassus Avenue, San Francisco, CA 94143, USA.
Melvin M ScheinmanDepartments of Medicine, Anatomy and Cellular and Molecular Pharmacology, University of California San Francisco, 500 Parnassus Avenue, San Francisco, CA 94143, USA.
Katriina Aalto-SetäläGladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA; Institute of Biomedical Technology, University of Tampere, Biokatu 12, 33520 Tampere, Finland.
Jonathan C MakielskiStem Cell and Regenerative Medicine Center, Cellular and Molecular Arrhythmia Research Program, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, Madison, WI 53792, USA.
Craig T JanuaryStem Cell and Regenerative Medicine Center, Cellular and Molecular Arrhythmia Research Program, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, Madison, WI 53792, USA.
Kevin E HealyDepartments of Bioengineering, and Material Science and Engineering, University of California, Berkeley, CA 94720, USA.
Timothy J KampStem Cell and Regenerative Medicine Center, Cellular and Molecular Arrhythmia Research Program, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, Madison, WI 53792, USA.
Shinya YamanakaGladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA; Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Bruce R ConklinGladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA; Departments of Medicine, Anatomy and Cellular and Molecular Pharmacology, University of California San Francisco, 500 Parnassus Avenue, San Francisco, CA 94143, USA. Electronic address: bconklin@gladstone.ucsf.edu.
Gladstone Institutes · USUniversity of Wisconsin–Madison · USUniversity of California, San Francisco · USKyoto University · JPUniversity of California, Berkeley · US
Funding
Transcriptional Networks During Cardiac DifferentiationP01HL089707 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI SRIVASTAVA, DEEPAK · 2008 to 2017
$20.4MThe Epigenetic Landscape of Heart DevelopmentU01HL098179 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI BOYER, LAURIE A, BRUNEAU, BENOIT GAETAN · 2009 to 2014
$10.0MInduced Pluripotent Stem Cells in the Understanding and Treatment of Heart DiseasU01HL100406 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI BRUNEAU, BENOIT GAETAN, CONKLIN, BRUCE R · 2009 to 2015
$9.4MMidwest Progenitor Cell ConsortiumU01HL099773 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI THOMSON, JAMES ALEXANDER · 2009 to 2015
$7.8MTissue Engineering with a Modular RASSL ToolboxR01HL060664 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI CONKLIN, BRUCE R · 1998 to 2012
$7.0MStructures of Protein Complexes Regulating Transcription in Enbryonic Stem CellsU01GM094614 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WEBB, PAUL · 2010 to 2014
$5.7MModeling metabolic interactions of liver and fat with integrated microphysiological systemsUH3TR000487 · NCATS · UNIVERSITY OF CALIFORNIA BERKELEY · PI HEALY, KEVIN EDWARD · 2014 to 2016
$2.9MDETERMINANTS OF CARDIAC REPOLARIZATIONR01HL060723 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI JANUARY, CRAIG T · 2000 to 2009
$2.8MDisease Specific Cardiac Tissue ModelsR01HL108677 · NHLBI · UNIVERSITY OF CALIFORNIA BERKELEY · PI CONKLIN, BRUCE R, HEALY, KEVIN EDWARD · 2011 to 2014
$2.4MEXTRAMULAR RESEARCH FACILITIES CONSTRUCTIONC06RR018928 · NCRR · J. DAVID GLADSTONE INSTITUTES · PI MAHLEY, ROBERT W. · 2003 to 2003
$2.1MDisease-Specific Integrated Microphysiological Human Tissue ModelsUH2TR000487 · NCATS · UNIVERSITY OF CALIFORNIA BERKELEY · PI HEALY, KEVIN EDWARD, LEE, LUKE P. · 2012 to 2013
$1.8MInduced pluripotent stem cells in the understanding and treatment of heart diseasR03HL096254 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI BRUNEAU, BENOIT GAETAN, CONKLIN, BRUCE R · 2009 to 2009
$48kNCATS NIH HHS UH2 TR000487NCATS NIH HHS UH2TR000487NCATS NIH HHS UH3 TR000487NCRR NIH HHS C06 RR018928NCRR NIH HHS RR18928NHLBI NIH HHS P01 HL089707NHLBI NIH HHS P01HL089707NHLBI NIH HHS R01 HL060664NHLBI NIH HHS R01 HL060723NHLBI NIH HHS R01HL07739NHLBI NIH HHS R01HL10867NHLBI NIH HHS R01 HL108677NHLBI NIH HHS R01HL60664NHLBI NIH HHS R03 HL096254NHLBI NIH HHS U01 HL098179NHLBI NIH HHS U01HL098179NHLBI NIH HHS U01HL09977NHLBI NIH HHS U01 HL099773NHLBI NIH HHS U01 HL100406NHLBI NIH HHS U01HL100406NIGMS NIH HHS U01 GM094614NIGMS NIH HHS U01GM09614
Abstract
Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca(2+)]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca(2+)]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca(2+). Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca(2+)]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na(+)-Ca(2+) exchange. These results suggest that LQTS mutations act partly on cytosolic Ca(2+) cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site.
Indexed as
Action PotentialsArrhythmias, CardiacCaffeineCalciumCell DifferentiationEther-A-Go-Go Potassium ChannelsFemaleGenotypeHumansInduced Pluripotent Stem CellsInfant, NewbornMiddle AgedMyocytes, CardiacNAV1.5 Voltage-Gated Sodium ChannelNifedipinePatch-Clamp TechniquesCaffeineCalciumEther-A-Go-Go Potassium ChannelsNAV1.5 Voltage-Gated Sodium ChannelNifedipineSCN5A protein, human
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