July 2022 - An in silico-in vitro pipeline for drug cardiotoxicity screening identifies ionic proarrhythmia mechanisms
Dr. András Horváth, Application Scientist (Nanion Technologies)
Title: Automating action potential pharmacology in hiPSC cardiomyocytes
PhD Student, Alex Clark, Christini Lab (Cornell University)
Title: An in silico-in vitro pipeline for drug cardiotoxicity screening identifies ionic proarrhythmia mechanisms
All new drugs are screened for their proarrhythmic potential using a method that is overly conservative and provides limited mechanistic insight, which can lead to the misclassification of beneficial drugs as proarrhythmic. Here, we developed an in silico-in vitro pipeline to circumvent these shortcomings. An iPSC-CM computational model was used to design electrophysiological voltage-clamp (VC) protocols for use during in vitro drug studies. Such VC data, along with AP recordings, were acquired from iPSC-CMs before and after treatment with a control solution or verapamil, cisapride, quinine, or quinidine. AP prolongation was seen in response to quinidine and quinine. The VC protocol identified all strong IKr blockers. The protocol also detected block of ICaL by verapamil and Ito by quinidine. The VC data also uncovered a previously unidentified If block by quinine, which was confirmed with experiments using a HEK-293 expression system and automated patch-clamp.
Date: 14. July 2022 (Join Live or Access On-Demand)
Time: 10 AM EDT, 4 PM CEST