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

Zhihan Zhao; Huan Lan; Ibrahim El-Battrawy; Xin Li; Fanis Buljubasic; Katherine Sattler; Gökhan Yücel; Siegfried Lang; Malte Tiburcy; Wolfram-Hubertus Zimmermann; Lukas Cyganek; Jochen Utikal; Thomas Wieland; Martin Borggrefe; Xiao-Bo Zhou; Ibrahim Akin

doi:10.1155/2018/6067096

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

Stem Cells Int. 2018 Jan 8:2018:6067096. doi: 10.1155/2018/6067096. eCollection 2018.

Authors

Zhihan Zhao^{1

2}, Huan Lan^{1

2

3}, Ibrahim El-Battrawy^{1

2}, Xin Li¹, Fanis Buljubasic^{1

2}, Katherine Sattler^{1

2}, Gökhan Yücel^{1

2}, Siegfried Lang^{1

2}, Malte Tiburcy^{2

4}, Wolfram-Hubertus Zimmermann^{2

4}, Lukas Cyganek^{2

5}, Jochen Utikal^{2

6

7}, Thomas Wieland^{2

8}, Martin Borggrefe^{1

2}, Xiao-Bo Zhou^{1

2

3}, Ibrahim Akin^{1

2}

Affiliations

¹ First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany.
² DZHK (German Center for Cardiovascular Research), Partner Sites, Heidelberg-Mannheim and Göttingen, Mannheim, Germany.
³ Key Laboratory of Medical Electrophysiology of Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China.
⁴ Institute of Pharmacology and Toxicology, University of Göttingen, Göttingen, Germany.
⁵ Stem Cell Unit, Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
⁶ Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁷ Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
⁸ Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Abstract

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, I_Na, I_Ca-L, I_Ca-T, I_f, I_NCX, I_K1, I_to, I_Kr, I_Ks I_KATP, I_K-pH, I_SK1-3, and I_SK4, 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 I_K1, I_KACh, I_SK, I_KNa, and TRPV1 currents contribute to AP duration. Isoprenaline increased I_Ca-L, I_f, and I_Ks but reduced I_Na and I_NCX, without an effect on I_to, I_K1, I_SK1-3, I_KATP, I_Kr, I_SK4, I_KNa, I_Cl-Ca, and I_TRPV1. 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.