Development of a high-throughput electrophysiological assay for the human ether-à-go-go related potassium channel hERG

Drug-induced prolongation of the QT interval via block of the hERG potassium channel is a major cause of attrition in drug development. The advent of automated electrophysiology systems has enabled the detection of hERG block earlier in drug discovery. In this study, we have evaluated the suitability of a second generation automated patch clamp instrument, the IonWorks Barracuda, for the characterization of hERG biophysics and pharmacology. All experiments were conducted with cells stably expressing hERG. Recordings were made in perforated patch mode either on a conventional patch clamp setup or on the IonWorks Barracuda. On the latter, all recordings were population recordings in 384-well patch plates. HERG channels activated with a V1/2=−3.2±1.6mV (n=178) on the IonWorks Barracuda versus −11.2±6.1mV (n=9) by manual patch clamp. On the IonWorks Barracuda, seal resistances and currents were stable (