期刊
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
卷 66, 期 3, 页码 246-256出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.vascn.2012.08.167
关键词
High content; Calcium transient; Cardiomyocyte; Cardiotoxicity; Arrhythmogenicity; Pharmacology
资金
- California Institute for Regenerative Medicine (CIRM) [RC1-00132-1]
- NIH [R37HL059502, R42HL086076, HHSN268200900044C, R01EB006200, U54HG005033]
- Sanford Children's Center
- Mather's heritable foundation
Current methods to measure physiological properties of cardiomyocytes and predict fatal arrhythmias that can cause sudden death, such as Torsade de Pointes, lack either the automation and throughput needed for early-stage drug discovery and/or have poor predictive value. To increase throughput and predictive power of in vitro assays, we developed kinetic imaging cytometry (KIC) for automated cell-by-cell analyses via intracellular fluorescence Ca2+ indicators. The KIC instrument simultaneously records and analyzes intracellular calcium concentration [Ca2+](i) at 30-ms resolution from hundreds of individual cells/well of 96-well plates in seconds, providing kinetic details not previously possible with well averaging technologies such as plate readers. Analyses of human embryonic stem cell and induced pluripotent stem cell-derived cardiomyocytes revealed effects of known cardiotoxic and arrhythmogenic drugs on kinetic parameters of Ca2+ dynamics, suggesting that KIC will aid in the assessment of cardiotoxic risk and in the elucidation of pathogenic mechanisms of heart disease associated with drugs treatment and/or genetic background. (C) 2012 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据