• Patchliner

    Most versatile automated patch clamp system on the market
  • Patchliner

    In-house production and QC of consumables
  • Patchliner

    More than 10 years experience in assay design and support
  • Dynamite8

    Automated Dynamic Clamp
  • Patchliner

    All features & benefits of manual patch clamp

2021 - A model-guided pipeline for drug cardiotoxicity screening with human stem-cell derived cardiomyocytes

icon pl  Patchliner Pre-Print Publication in bioRxiv (2021)

Clark A. P., Wie S., Krogh-Madsen T., Christini D. J.


bioRxiv (2021) doi:10.1101/2021.09.10.459625


New therapeutic compounds go through a preclinical drug cardiotoxicity screening process that is overly conservative and provides limited mechanistic insight, leading to the misclassification of potentially beneficial drugs as proarrhythmic. There is a need to develop a screening paradigm that maintains this high sensitivity, while ensuring non-cardiotoxic compounds pass this phase of the drug approval process. In this study, we develop an in vitro-in silico pipeline using human induced stem-cell derived cardiomyocytes (iPSC-CMs) to address this problem. The pipeline includes a model-guided optimization that produces a voltage-clamp (VC) protocol to determine drug block of seven cardiac ion channels. Such VC data, along with action potential (AP) recordings, were acquired from iPSC-CMs before and after treatment with a control solution or a low-, intermediate-, or high-risk drug. We identified significant AP prolongation (a proarrhythmia indicator) in two high-risk drugs and, from the VC data, determined strong ion channel blocks that led to the AP changes. The VC data also uncovered an undocumented funny current (If) block by quinine, which we confirmed with experiments using a HEK-293 expression line. We present a new approach to cardiotoxicity screening that simultaneously evaluates proarrhythmia risk (e.g. AP prolongation) and mechanism (e.g. channel block) from iPSC-CMs.

Download here

Back to Overview

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies). You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.