scholarly journals Ion Channel Expression and Characterization in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Zhihan Zhao ◽  
Huan Lan ◽  
Ibrahim El-Battrawy ◽  
Xin Li ◽  
Fanis Buljubasic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Ion Channels ◽  
Ion Channel ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Biological Study ◽  
Adrenergic Stimulation ◽  
Cell Therapies ◽  
Channel Expression ◽  
Induced Pluripotent

Background. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are providing new possibilities for the biological study, cell therapies, and drug discovery. However, the ion channel expression and functions as well as regulations in hiPSC-CMs still need to be fully characterized. Methods. Cardiomyocytes were derived from hiPS cells that were generated from two healthy donors. qPCR and patch clamp techniques were used for the study. Results. In addition to the reported ion channels, INa, ICa-L, ICa-T, If, INCX, IK1, Ito, IKr, IKs IKATP, IK-pH, ISK1–3, and ISK4, we detected both the expression and currents of ACh-activated (KACh) and Na+-activated (KNa) K+, volume-regulated and calcium-activated (Cl-Ca) Cl−, and TRPV channels. All the detected ion currents except IK1, IKACh, ISK, IKNa, and TRPV1 currents contribute to AP duration. Isoprenaline increased ICa-L, If, and IKs but reduced INa and INCX, without an effect on Ito, IK1, ISK1–3, IKATP, IKr, ISK4, IKNa, ICl-Ca, and ITRPV1. Carbachol alone showed no effect on the tested ion channel currents. Conclusion. Our data demonstrate that most ion channels, which are present in healthy or diseased cardiomyocytes, exist in hiPSC-CMs. Some of them contribute to action potential performance and are regulated by adrenergic stimulation.

scholarly journals Characterizing Human Ion Channels in Induced Pluripotent Stem Cell–Derived Neurons

2012 ◽  
Vol 17 (9) ◽  
pp. 1264-1272 ◽  
Author(s):  
Alison Haythornthwaite ◽  
Sonja Stoelzle ◽  
Alexander Hasler ◽  
Andrea Kiss ◽  
Johannes Mosbacher ◽  
...  
Keyword(s):  
Stem Cell ◽  
Ion Channels ◽  
Patch Clamp ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Excitable Cells ◽  
Automated Patch Clamp ◽  
Induced Pluripotent ◽  
Two Populations ◽  
A Current

Neurons derived from human-induced pluripotent stem cells were characterized using manual and automated patch-clamp recordings. These cells expressed voltage-gated Na+ (Nav), Ca2+ (Cav), and K+ (Kv) channels as expected from excitable cells. The Nav current was TTX sensitive, IC50 = 12 ± 6 nM ( n = 5). About 50% of the Cav current was blocked by 10 µM of the L-type channel blocker nifedipine. Two populations of the Kv channel were present in different proportions: an inactivating (A-type) and a noninactivating type. The A-type current was sensitive to 4-AP and TEA (IC50 = 163 ± 93 µM; n = 3). Application of γ-aminobutyric acid (GABA) activated a current sensitive to the GABAA receptor antagonist bicuculline, IC50 = 632 ± 149 nM ( n = 5). In both devices, comparable action potentials were generated in the current clamp. With unbiased, automated patch clamp, about 40% of the cells expressed Nav currents, whereas visual guidance in manual patch clamp provided almost a 100% success rate of patching “excitable cells.” These results show high potential for pluripotent stem cell–derived neurons as a useful model for drug discovery, in combination with automated patch-clamp recordings for high-throughput and high-quality drug assessments at human neuronal ion channels in their correct cellular background.

scholarly journals The Emergence of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) as a Platform to Model Arrhythmogenic Diseases

2020 ◽  
Vol 21 (2) ◽  
pp. 657 ◽  
Author(s):  
Marc Pourrier ◽  
David Fedida
Keyword(s):  
Stem Cell ◽  
Ion Channel ◽  
Pluripotent Stem Cell ◽  
Molecular Mechanisms ◽  
Induced Pluripotent Stem Cell ◽  
Transgenic Animal ◽  
Cardiac Diseases ◽  
Disease Phenotype ◽  
Induced Pluripotent

There is a need for improved in vitro models of inherited cardiac diseases to better understand basic cellular and molecular mechanisms and advance drug development. Most of these diseases are associated with arrhythmias, as a result of mutations in ion channel or ion channel-modulatory proteins. Thus far, the electrophysiological phenotype of these mutations has been typically studied using transgenic animal models and heterologous expression systems. Although they have played a major role in advancing the understanding of the pathophysiology of arrhythmogenesis, more physiological and predictive preclinical models are necessary to optimize the treatment strategy for individual patients. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have generated much interest as an alternative tool to model arrhythmogenic diseases. They provide a unique opportunity to recapitulate the native-like environment required for mutated proteins to reproduce the human cellular disease phenotype. However, it is also important to recognize the limitations of this technology, specifically their fetal electrophysiological phenotype, which differentiates them from adult human myocytes. In this review, we provide an overview of the major inherited arrhythmogenic cardiac diseases modeled using hiPSC-CMs and for which the cellular disease phenotype has been somewhat characterized.

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