• CardioExcyte 96

    结合阻抗与类MEA记录
  • CardioExcyte 96

    用于心脏安全筛选
  • CardioExcyte 96

    下一代非标记细胞分析
  • CardioExcyte 96

    直观的数据分析&心律失常检测

2017 - Frequency-Dependent Multi-Well Cardiotoxicity Screening Enabled by Optogenetic Stimulation

Icon CE  CardioExcyte 96 publication in International Journal of Molecular Sciences

Authors:
Rehnelt S., Malan D., Juhasz K., Wolters B., Doerr L., Beckler M., Kettenhofen R., Bohlen H., Bruegmann T., Sasse P.

Journal:
International Journal of Molecular Sciences (2017) 18:2634


Abstract:

Side effects on cardiac ion channels causing lethal arrhythmias are one major reason for drug withdrawals from the market. Field potential (FP) recording from cardiomyocytes, is a well-suited tool to assess such cardiotoxic effects of drug candidates in preclinical drug development, but it is currently limited to the spontaneous beating of the cardiomyocytes and manual analysis. Herein, we present a novel optogenetic cardiotoxicity screening system suited for the parallel automated frequency-dependent analysis of drug effects on FP recorded from human-induced pluripotent stem cell-derived cardiomyocytes. For the expression of the light-sensitive cation channel Channelrhodopsin-2, we optimised protocols using virus transduction or transient mRNA transfection. Optical stimulation was performed with a new light-emitting diode lid for a 96-well FP recording system. This enabled reliable pacing at physiologically relevant heart rates and robust recording of FP. Thereby we detected rate-dependent effects of drugs on Na+, Ca2+ and K+ channel function indicated by FP prolongation, FP shortening and the slowing of the FP downstroke component, as well as generation of afterdepolarisations. Taken together, we present a scalable approach for preclinical frequency-dependent screening of drug effects on cardiac electrophysiology. Importantly, we show that the recording and analysis can be fully automated and the technology is readily available using commercial products.


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