ArticleFrontiers in pharmacology2016
Ca(2+)-Currents in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Effects of Two Different Culture Conditions.
Article in Frontiers in pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 55 citations in OpenAlex.
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- In situ monolayer patch clamp of acutely stimulated human iPSC-derived cardiomyocytes promotes consistent electrophysiological responses to SK channel inhibition.Scientific reports · 2024Article
- Model construction and clinical therapeutic potential of engineered cardiac organoids for cardiovascular diseases.Biomaterials translational · 2024Review
- iPSC-cardiomyocytes in the preclinical prediction of candidate pharmaceutical toxicity.Frontiers in pharmacology · 2024Review
- Modulating cardiac physiology in engineered heart tissue with the bidirectional optogenetic tool BiPOLES.Pflugers Archiv : European journal of physiology · 2023Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- Human induced pluripotent stem cell-derived cardiomyocytes as an electrophysiological model: Opportunities and challenges-The Hamburg perspective.Frontiers in physiology · 2023Review
- Regulation of APD and Force by the NaCells · 2022Article
- Tissue Engineering Techniques for Induced Pluripotent Stem Cell Derived Three-Dimensional Cardiac Constructs.Tissue engineering. Part B, Reviews · 2022Review
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- From engineered heart tissue to cardiac organoid.Theranostics · 2022Review
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- Recent Advances in Maturation of Pluripotent Stem Cell-Derived Cardiomyocytes Promoted by Mechanical Stretch.Medical science monitor : international medical journal of experimental and clinical research · 2021Review
- Next generation of heart regenerative therapies: progress and promise of cardiac tissue engineering.NPJ Regenerative medicine · 2021Review
- Human iPSC modeling of heart disease for drug development.Cell chemical biology · 2021Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) provide a unique opportunity to study human heart physiology and pharmacology and repair injured hearts. The suitability of hiPSC-CM critically depends on how closely they share physiological properties of human adult cardiomyocytes (CM). Here we investigated whether a 3D engineered heart tissue (EHT) culture format favors maturation and addressed the L-type Ca(2+)-current (ICa,L) as a readout. The results were compared with hiPSC-CM cultured in conventional monolayer (ML) and to our previous data from human adult atrial and ventricular CM obtained when identical patch-clamp protocols were used. HiPSC-CM were two- to three-fold smaller than adult CM, independently of culture format [capacitance ML 45 ± 1 pF (n = 289), EHT 45 ± 1 pF (n = 460), atrial CM 87 ± 3 pF (n = 196), ventricular CM 126 ± 8 pF (n = 50)]. Only 88% of ML cells showed ICa, but all EHT. Basal ICa density was 10 ± 1 pA/pF (n = 207) for ML and 12 ± 1 pA/pF (n = 361) for EHT and was larger than in adult CM [7 ± 1 pA/pF (p < 0.05, n = 196) for atrial CM and 6 ± 1 pA/pF (p < 0.05, n = 47) for ventricular CM]. However, ML and EHT showed robust T-type Ca(2+)-currents (ICa,T). While (-)-Bay K 8644, that activates ICa,L directly, increased ICa,Lto the same extent in ML and EHT, β1- and β2-adrenoceptor effects were marginal in ML, but of same size as (-)-Bay K 8644 in EHT. The opposite was true for serotonin receptors. Sensitivity to β1 and β2-adrenoceptor stimulation was the same in EHT as in adult CM (-logEC50: 5.9 and 6.1 for norepinephrine (NE) and epinephrine (Epi), respectively), but very low concentrations of Rp-8-Br-cAMPS were sufficient to suppress effects (-logEC50: 5.3 and 5.3 respectively for NE and Epi). Taken together, hiPSC-CM express ICa,L at the same density as human adult CM, but, in contrast, possess robust ICa,T. Increased effects of catecholamines in EHT suggest more efficient maturation.
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