studies of iPS-CMs overexpressing KCNJ2

iPSC-derived cardiomyocytes (iPSC-CMs) are relatively electrophysiologically and structurally immature compared to primary cardiomyocytes, hindering their widespread application in basic and translational research. The inwardly rectifying potassium channel Kir2.1, encoded by KCNJ2, plays a major role in the plateau phase of cardiac action potential repolarization, helping to stabilize the resting membrane potential. However, due to the lower current density of IK1 encoding Kir2.1, iPSC-CMs are prone to exhibit auto-arrhythmias and further exhibit slower sodium uptake as well as impaired sarcoplasmic reticulum-mediated calcium handling. In this project, normal human iPSC-CMs were obtained by myocardial directional differentiation technology, and a lentivirus-mediated KCNJ2 overexpression system of iPSC-CMs was constructed. The effect and mechanism of expression on the maturation of iPSC-CMs will open up new avenues for promoting the maturation of iPSC-CMs and subsequent applications.

诱导多能干细胞衍生心肌细胞（iPSC-derived cardiomyocytes, iPSC-CMs）与原代心肌细胞相比，电生理特性与结构均相对未成熟，这一缺陷阻碍了其在基础与转化研究中的广泛应用。由KCNJ2基因编码的内向整流钾通道Kir2.1（inwardly rectifying potassium channel Kir2.1），在心脏动作电位复极的平台期发挥核心作用，有助于稳定静息膜电位。然而，由于iPSC-CMs中编码Kir2.1的IK1电流密度较低，其易出现自发性心律失常，同时还表现出钠摄取速率减慢以及肌浆网介导的钙处理功能受损。本研究通过心肌定向分化技术获取正常人类iPSC-CMs，并构建了慢病毒介导的KCNJ2过表达iPSC-CMs体系。该体系中KCNJ2过表达对iPSC-CMs成熟的影响及其作用机制，将为促进iPSC-CMs成熟及其后续应用开辟新途径。