Cellular Dynamics International, Madison, Wisconsin, USA.
Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H2006-17. doi: 10.1152/ajpheart.00694.2011. Epub 2011 Sep 2.
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.
人诱导多能干细胞（hiPSCs）可分化为功能性心肌细胞；然而，hiPSC 衍生的心肌细胞的电生理特性尚未完全表征。我们对高纯度的 hiPSC 衍生的心肌细胞进行了详细的电生理特征分析。使用穿孔贴片方法从自发搏动的心肌细胞中记录动作电位（AP），具有心房、结状和心室样特性。心室样 AP 更为常见，最大舒张电位接近人心肌细胞，AP 持续时间在正常人心电图 QT 间期范围内，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。用 E4031 诱导早期后除极（EAD），并依赖于心动过缓，EAD 峰值电压与 EAD 起飞电位呈反比变化。研究了包括钠（I(Na)）、L 型钙（I(Ca)）、超极化激活起搏（I(f)）、瞬间外向钾（I(to)）、内向整流钾（I(K1)）和快速激活和缓慢激活的延迟整流钾（I(Kr)和 I(Ks)）在内的七种离子电流的门控特性。高纯度和大量的细胞数量也使自动膜片钳分析成为可能。我们得出结论，这些 hiPSC 衍生的心肌细胞具有离子电流和通道门控特性，其 AP 和 EAD 与人心肌细胞报道的特性在数量上相似。这些 hiPSC 衍生的心肌细胞具有可以用于高通量测定的额外优势，并且具有影响心血管研究和治疗应用的多个领域的潜力。
