Investigation of in vitro IKr/hERG assays under physiological temperature conditions using the semi-automated patch-clamp system QPatch Compact with temperature control system

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 I_Kr/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 investigated whole-cell patch-clamp measurements of hERG currents under physiological temperature conditions (36-37°C) using the semi-automated patch-clamp system QPatch Compact using the recommended best practices.