ArticleJournal of molecular and cellular cardiology2013
Identification and characterization of a transient outward K+ current in human induced pluripotent stem cell-derived cardiomyocytes.
Article in Journal of molecular and cellular cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 66 citations in OpenAlex.
- Electromechanical modelling and simulation of human-induced pluripotent stem cell-derived cardiomyocytes predict drug-induced contractility effects.The Journal of physiology · 2026Article
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- Modeling drug-induced mitochondrial toxicity with human primary cardiomyocytes.Science China. Life sciences · 2024Article
- iPSC-cardiomyocytes in the preclinical prediction of candidate pharmaceutical toxicity.Frontiers in pharmacology · 2024Review
- hiPSC-derived cardiomyocytes as a model to study the role of small-conductance CaFrontiers in cell and developmental biology · 2024Review
- Targeted activation of human ether-à-go-go-related gene channels rescues electrical instability induced by the R56Q+/- long QT syndrome variant.Cardiovascular research · 2023Article
- Synergistic effects of hormones on structural and functional maturation of cardiomyocytes and implications for heart regeneration.Cellular and molecular life sciences : CMLS · 2023Review
- Systematic discovery of transcription factors that improve hPSC-derived cardiomyocyte maturation via temporal analysis of bioengineered cardiac tissues.APL bioengineering · 2023Article
- Empagliflozin reduces arrhythmogenic effects in rat neonatal and human iPSC-derived cardiomyocytes and improves cytosolic calcium handling at least partially independent of NHE1.Scientific reports · 2023Article
- Metformin Reduces Potassium Currents and Prolongs Repolarization in Non-Diabetic Heart.International journal of molecular sciences · 2022Article
- Maturation of Stem Cell-Derived Cardiomyocytes: Foe in Translation Medicine.International journal of stem cells · 2021Review
- Maturing heart muscle cells: Mechanisms and transcriptomic insights.Seminars in cell & developmental biology · 2021Review
- Modeling Cardiomyopathies in a Dish: State-of-the-Art and Novel Perspectives on hiPSC-Derived Cardiomyocytes Maturation.Biology · 2021Article
- Overlap Arrhythmia Syndromes Resulting from Multiple Genetic Variations Studied in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.International journal of molecular sciences · 2021Article
- AnFrontiers in physiology · 2021Article
- Comparison of the Simulated Response of ThreeFrontiers in pharmacology · 2021Article
- Syncytium cell growth increases Kir2.1 contribution in human iPSC-cardiomyocytes.American journal of physiology. Heart and circulatory physiology · 2020Article
- Genetic Algorithm For Fitting Cardiac Cell Biophysical Model Formulations.Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference · 2020Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe ability to recapitulate mature adult phenotypes is critical to the development of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) as models of disease. The present study examines the characteristics of the transient outward current (Ito) and its contribution to the hiPSC-CM action potential (AP).
methodEmbryoid bodies were made from a hiPS cell line reprogrammed with Oct4, Nanog, Lin28 and Sox2. Sharp microelectrodes were used to record APs from beating-clusters (BC) and patch-clamp techniques were used to record Ito in single hiPSC-CM. mRNA levels of Kv1.4, KChIP2 and Kv4.3 were quantified from BCs.
resultsBCs exhibited spontaneous beating (60.5±2.6 bpm) and maximum-diastolic-potential (MDP) of 67.8±0.8 mV (n=155). A small 4-aminopyridine-sensitive phase-1-repolarization was observed in only 6/155 BCs. A robust Ito was recorded in the majority of cells (13.7±1.9 pA/pF at +40 mV; n=14). Recovery of Ito from inactivation (at -80 mV) showed slow kinetics (τ1=200±110 ms (12%) and τ2=2380±240 ms (80%)) accounting for its minimal contribution to the AP. Transcript data revealed relatively high expression of Kv1.4 and low expression of KChIP2 compared to human native ventricular tissues. Mathematical modeling predicted that restoration of IK1 to normal levels would result in a more negative MDP and a prominent phase-1-repolarization.
conclusionThe slow recovery kinetics of Ito coupled with a depolarized MDP account for the lack of an AP notch in the majority of hiPSC-CM. These characteristics reveal a deficiency for the development of in vitro models of inherited cardiac arrhythmia syndromes in which Ito-induced AP notch is central to the disease phenotype.
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