High-throughput evaluation of cardiac safety targets Nav1.5 and Cav1.2 in axoCells™ hiPSC-derived cardiomyocytes using Qube 384

Cardiac ion channels present highly attractive therapeutic targets in the cardiovascular system. They are also a major factor in drug-induced cardiotoxicity. This makes electrophysiological studies of hiPSC-CMs vital to their usage in drug discovery and safety studies.

However, historically, these studies have been limited by the labour-intensive and low-throughput nature of manual patch clamp electrophysiology. In addition, limitations in the technique have impacted the quality of the data obtained, challenging its physiological relevance.

This study aims to demonstrate the utilisation of Sophion’s Qube 384 automated patch clamp (APC) platform for high-throughput electrophysiological characterisation and compound screening of cardiac safety targets, Na_V1.5 and Ca_V1.2, in axoCells™ hiPSC-derived ventricular CMs.

In addition, it aims to demonstrate the possibility of using perforated patch clamp recordings to increase the physiological
relevance of Ca_V1.2 and action-potential measurements.

The possibility of performing perforated patch-clamp recordings of hiPSC-derived CMs on an APC platform, as demonstrated in the proof-of-concept experiments here, opens a new avenue for more physiologically relevant and improved pharmacological studies due to:

• Preservation of the intracellular signaling
• Reduced current rundown
• Limited fluoride-related artifacts