High purity human-induced pluripotent stem cell-derived cardiomyocytes: electrophysiological properties of action potentials and ionic currents
High purity human-induced pluripotent stem cell-derived cardiomyocytes: electrophysiological properties of action potentials and ionic currents
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DOI：
10.1152/ajpheart.00694.2011
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发表时间：
2011-11-01
影响因子：
4.8
通讯作者：
January, Craig T.
中科院分区：
文献类型：
--
作者：
Ma, Junyi;Guo, Liang;January, Craig T.
马军，郭L，费思杰，安生BD，汤姆森JA，坎普TJ，Kolaja KL，Swanson BJ，1月CT。高纯度人类诱导的多能干细胞来源的心肌细胞：动作电位和离子电流的电生理特性。Am J Physiol心脏圈Physiol 301：H2006-H2017,2011。2011年9月2日首次发表；doi:10.1152/ajpheart.00694.2011.-Human-induced多能干细胞可以分化为有功能的心肌细胞；然而，HIPSC来源的心肌细胞的电生理特性尚未完全确定。我们对高纯度的HiPSC来源的心肌细胞进行了详细的电生理表征。动作电位(AP)是由自发性搏动的心肌细胞用穿孔贴片方法记录的，具有房性、结性和室性。室性AP更为常见，其最大舒张期电位接近人类心肌细胞，AP持续时间在正常人心电图QT间期的范围内，AP对多种药物(河豚毒素、硝苯地平和E4031)表现出预期的敏感性。E4031诱发的早期后除极(EAD)依赖于心动过缓，EAD的峰值电压与EAD的起搏电位成反比。本文研究了钠(I-Na)、L型钙(I-Ca)、超极化激活起搏器(I-f)、瞬时外向钾(I-TO)、内向整流钾(I-K1)和延迟整流钾的快、慢激活分量(分别为I-Kr和I-Ks)7种离子电流的门控特性。高纯度和大量细胞数量也使自动化膜片钳分析成为可能。我们得出结论，这些来源于HiPSC的心肌细胞在其AP和EADS下具有离子电流和通道门控特性，这在数量上与已报道的人类心肌细胞相似。这些来自HiPSC的心肌细胞还有一个额外的优势，即它们可以用于高通量分析，并且它们有可能影响心血管研究和治疗应用的多个领域。
Ma J, Guo L, Fiene SJ, Anson BD, Thomson JA, Kamp TJ, Kolaja KL, Swanson BJ, January CT. High purity human-induced pluripotent stem cell-derived cardiomyocytes: electrophysiological properties of action potentials and ionic currents. Am J Physiol Heart Circ Physiol 301: H2006-H2017, 2011. First published September 2, 2011; doi:10.1152/ajpheart.00694.2011.-Human-induced pluripotent stem cells (hiPSCs) can differentiate into functional cardiomyocytes; however, the electrophysiological properties of hiPSC-derived cardiomyocytes have yet to be fully characterized. We performed detailed electrophysiological characterization of highly pure hiPSC-derived cardiomyocytes. Action potentials (APs) were recorded from spontaneously beating cardiomyocytes using a perforated patch method and had atrial-, nodal-, and ventricular-like properties. Ventricular-like APs were more common and had maximum diastolic potentials close to those of human cardiac myocytes, AP durations were within the range of the normal human electrocardiographic QT interval, and APs showed expected sensitivity to multiple drugs (tetrodotoxin, nifedipine, and E4031). Early afterdepolarizations (EADs) were induced with E4031 and were bradycardia dependent, and EAD peak voltage varied inversely with the EAD take-off potential. Gating properties of seven ionic currents were studied including sodium (I-Na), L-type calcium (I-Ca), hyperpolarization-activated pacemaker (I-f), transient outward potassium (I-to), inward rectifier potassium (I-K1), and the rapidly and slowly activating components of delayed rectifier potassium (I-Kr and I-Ks, respectively) current. The high purity and large cell numbers also enabled automated patch-clamp analysis. We conclude that these hiPSC-derived cardiomyocytes have ionic currents and channel gating properties underlying their APs and EADs that are quantitatively similar to those reported for human cardiac myocytes. These hiPSC-derived cardiomyocytes have the added advantage that they can be used in high-throughput assays, and they have the potential to impact multiple areas of cardiovascular research and therapeutic applications.