Long-term in vitro recording of cardiac action potentials on microelectrode arrays for chronic cardiotoxicity assessment

长期体外记录微电极阵列上的心脏动作电位以评估慢性心脏毒性

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作者:Giuseppina Iachetta, Giovanni Melle, Nicolò Colistra, Francesco Tantussi, Francesco De Angelis, Michele Dipalo

Abstract

The reliable identification of chronic cardiotoxic effects in in vitro screenings is fundamental for filtering out toxic molecular entities before in vivo animal experimentation and clinical trials. Present techniques such as patch-clamp, voltage indicators, and standard microelectrode arrays do not offer at the same time high sensitivity for measuring transmembrane ion currents and low-invasiveness for monitoring cells over long time. Here, we show that optoporation applied to microelectrode arrays enables measuring action potentials from human-derived cardiac syncytia for more than 1 continuous month and provides reliable data on chronic cardiotoxic effects caused by known compounds such as pentamidine. The technique has high potential for detecting chronic cardiotoxicity in the early phases of drug development.

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