Keshmiri Neghab Hoda, Soheilifar Mohammad Hasan, Saboury Ali Akbar, Goliaei Bahram, Hong Jun, Esmaeeli Djavid Gholamreza
Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran.
Institutes of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
J Lasers Med Sci. 2021 Jul 4;12:e32. doi: 10.34172/jlms.2021.32. eCollection 2021.
Non-clinical cardiovascular drug safety assessment is the main step in the progress of new pharmaceutical products. Cardiac drug safety testing focuses on a delayed rectifier potassium channel block and QT interval prolongation, whereas optogenetics is a powerful technology for modulating the electrophysiological properties of excitable cells. For this purpose, the blue light-gated ion channel, channelrhodopsin-2 (ChR2), has been introduced into isolated primary neonatal cardiomyocytes via a lentiviral vector. After being subjected to optical stimulation, transmembrane potential and intracellular calcium were assessed. Here, we generated cardiomyocytes expressing ChR2 (light-sensitive protein), that upon optical stimulation, the cardiomyocytes depolarized result from alterations of membrane voltage and intracellular calcium. This cell model was easily adapted to a cell culture system in a laboratory, making this method very attractive for therapeutic research on cardiac optogenetics.
非临床心血管药物安全性评估是新药研发过程中的主要环节。心脏药物安全性测试主要关注延迟整流钾通道阻滞和QT间期延长，而光遗传学是一种调节可兴奋细胞电生理特性的强大技术。为此，通过慢病毒载体将蓝光门控离子通道——通道视紫红质-2（ChR2）导入分离的原代新生心肌细胞。在接受光刺激后，评估跨膜电位和细胞内钙。在此，我们构建了表达ChR2（光敏感蛋白）的心肌细胞，经光刺激后，心肌细胞去极化是由膜电压和细胞内钙的变化引起的。该细胞模型很容易适用于实验室的细胞培养系统，使得这种方法对心脏光遗传学治疗研究极具吸引力。
