Zhao Zhihan, Lan Huan, El-Battrawy Ibrahim, Li Xin, Buljubasic Fanis, Sattler Katherine, Yücel Gökhan, Lang Siegfried, Tiburcy Malte, Zimmermann Wolfram-Hubertus, Cyganek Lukas, Utikal Jochen, Wieland Thomas, Borggrefe Martin, Zhou Xiao-Bo, Akin Ibrahim
First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany.
DZHK (German Center for Cardiovascular Research), Partner Sites, Heidelberg-Mannheim and Göttingen, Mannheim, Germany.
Stem Cells Int. 2018 Jan 8;2018:6067096. doi: 10.1155/2018/6067096. eCollection 2018.
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.
Cardiomyocytes were derived from hiPS cells that were generated from two healthy donors. qPCR and patch clamp techniques were used for the study.
In addition to the reported ion channels, I, I, I, I, I, I, I, I, I I, I, I, and I, 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, I, I, I, and TRPV1 currents contribute to AP duration. Isoprenaline increased I, I, and I but reduced I and I, without an effect on I, I, I, I, I, I, I, I, and I. Carbachol alone showed no effect on the tested ion channel currents.
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.
人诱导多能干细胞衍生的心肌细胞(hiPSC-CMs)为生物学研究、细胞治疗和药物发现提供了新的可能性。然而,hiPSC-CMs中的离子通道表达、功能及其调控仍需充分表征。
心肌细胞来源于两名健康供体产生的hiPS细胞。采用qPCR和膜片钳技术进行研究。
除了已报道的离子通道I、I、I、I、I、I、I、I、II、I、I和I外,我们还检测到了乙酰胆碱激活的(KACh)和钠激活的(KNa)钾通道、容积调节和钙激活的(Cl-Ca)氯通道以及TRPV通道的表达和电流。除I、I、I、I和TRPV1电流外,所有检测到的离子电流均对动作电位时程有影响。异丙肾上腺素增加I、I和I,但降低I和I,对I、I、I、I、I、I、I、I和I无影响。单独使用卡巴胆碱对所测试的离子通道电流无影响。
我们的数据表明,健康或患病心肌细胞中存在的大多数离子通道也存在于hiPSC-CMs中。其中一些离子通道对动作电位表现有贡献,并受肾上腺素能刺激的调节。