Comparative study of hERG channels under physiological temperature (CiPA) conditions using high-throughput automated patch-clamp QPatch and Qube

Cardiac ion channel activity is crucial for generating cardiac action potentials with proper timing and duration. Drug-induced impairment of these ion channels can cause abnormal cardiac activity, including QT interval prolongation, ventricular arrhythmia, and, in the most severe cases, sudden death. These adverse effects are among the leading reasons for drug withdrawal from the market or the denial of regulatory approval for new therapeutic candidates. The ICH E14/S7B Q&A released in August 2022 provided recommended conditions for best practices for in vitro assay of IKr/hERG to maintain reproducibility and consistency in evaluations. These recommendations include testing under
physiological temperature conditions, as well as considering factors such as voltage protocols. In this study, we assessed the inhibitory effects of a compound on hERG channels under physiological temperature conditions (35° C) through whole-cell patch clamp experiments using the automated patch clamp system QPatch and Qube 384.