Development and validation of a Qube automated patch clamp hERG assay at physiological temperatures
The development of Automated Patch Clamp (APC) technology over the last 20 years has transformed the research and development process for identifying novel drugs for ion channel targets(1). Furthermore, it has been widely implemented in cardiac safety pharmacology screening by pharma and contract research organisations(1,2).
The adoption of APC as a screening tool has gathered pace over the last 10 years, which may in part be attributed to the introduction of the Comprehensive in Vitro Proarrhythmia Assay initiative (CiPA and JiCSA in Japan). Several published studies have confirmed that the high quality potency data derived from APC screening can be inserted into in silico models of human ventricular action potentials to accurately predict proarrhythmic risk(1,2,3,4).
Most commercially available APC cardiac safety assays have historically been performed at room temperature. However, it is widely acknowledged that temperature can affect the hERG potency of certain agents (e.g. erythromycin, sotalol)(4,5), which underlies the basis of why the FDA recommend performing GLP hERG studies at physiological temperatures (6).
Therefore, an APC assay performed at physiological temperatures will benefit from the combination of greater throughput with enhanced sensitivity for compounds that exhibit temperature-dependent inhibition.