Electronic "expression" of the inward rectifier in cardiocytes derived from human-induced pluripotent stem cells.
Electronic "expression" of the inward rectifier in cardiocytes derived from human-induced pluripotent stem cells.
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DOI：
10.1016/j.hrthm.2013.09.061
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发表时间：
2013-12
期刊：
影响因子：
5.5
通讯作者：
Rasmusson, Randall L.
中科院分区：
文献类型：
--
作者：
Bett, Glenna C. L.;Kaplan, Aaron D.;Lis, Agnieszka;Cimato, Thomas R.;Tzanakakis, Emmanuel S.;Zhou, Qinlian;Morales, Michael J.;Rasmusson, Randall L.
人诱导多能干细胞（h-iPSC）衍生的心肌细胞是研究人肌细胞功能和功能障碍的独特模型，特别是来自遗传性疾病患者。它们也被认为是药物安全测试的重大进步。然而，这些细胞在应用于定量动作电位（AP）分析时具有相当大的未开发的潜在限制。一个主要因素是自发活动，以及由此产生的AP参数的变异性和潜在的异常行为。证明使用计算机接口电子表达IK 1的效果，IK 1是h-iPSC衍生的心肌细胞中缺乏的主要组分。开发了计算机接口以在全细胞电压钳下在细胞中表达合成IK 1。电子IK 1表达建立了生理静息电位，消除自发活动，减少自发早期和延迟后去极化，并降低AP变异性。启动的AP具有经典的快速上升和尖峰和圆顶形态与新鲜分离的人肌细胞的数据一致，以及心室和心房细胞易于识别的复极属性。应用1 μM BayK-8644导致h-iPSC衍生的心肌细胞中异常AP缩短。当IK 1电子表达时，BayK-8644延长了AP，与天然心肌细胞的现有结果一致。IK 1的电子表达是一种简单而稳健的方法，可显著改善AP的生理行为和h-iPSC衍生的心肌细胞的电特性。增加的稳定性使得该制剂能够用于AP参数的受控定量分析，药物反应性、遗传疾病和动态行为恢复概况。
Human induced pluripotent stem cell (h-iPSC)-derived cardiac myocytes are a unique model in which to study human myocyte function and dysfunction, especially from patients with genetic disorders. They are also considered a major advance for drug safety testing. However, these cells have considerable unexplored potential limitations when applied to quantitative action potential (AP) analysis. One major factor is spontaneous activity, and resulting variability and potentially anomalous behavior in AP parameters. To demonstrate the effect of using an in silico interface to electronically express IK1, a major component lacking in h-iPSC-derived cardiac myocytes. An in silico interface was developed to express synthetic IK1 in cells under whole cell voltage clamp. Electronic IK1 expression established a physiological resting potential, eliminated spontaneous activity, reduced spontaneous early and delayed after depolarizations, and decreased AP variability. Initiated APs had the classic rapid upstroke and spike and dome morphology consistent with data from freshly isolated human myocytes, and the readily recognizable repolarization attributes of ventricular and atrial cells. Application of 1 μM BayK-8644 resulted in anomalous AP shortening in h-iPSC-derived cardiac myocytes. When IK1 was electronically expressed, BayK-8644 lengthened the AP, consistent with existing results on native cardiac myocytes. Electronic expression of IK1 is a simple and robust method to significantly improve the physiological behavior of the AP and electrical profile of h-iPSC-derived cardiac myocytes. Increased stability enables this preparation to be used for controlled quantitative analysis of AP parameters e.g., drug responsiveness, genetic disorders, and dynamic behavior restitution profiles.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5
作者：
Jonsson, Malin K. B.;Vos, Marc A.;van Veen, Toon A. B.
通讯作者：
van Veen, Toon A. B.
DOI：
10.1109/memb.2009.931792
发表时间：
2009-03
期刊：
IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society
影响因子：
--
作者：
Bursac N
通讯作者：
Bursac N
DOI：
10.1161/circep.111.973420
发表时间：
2013-02
期刊：
Circulation. Arrhythmia and electrophysiology
影响因子：
--
作者：
Lieu DK;Fu JD;Chiamvimonvat N;Tung KC;McNerney GP;Huser T;Keller G;Kong CW;Li RA
通讯作者：
Li RA
影响因子：
64.8
作者：
ISENBERG, G
通讯作者：
ISENBERG, G