Characterization and Functional Validation of CHO hERG with IonFlux HT Single Cell Mode

HERG (human ether-a-go-go-related gene) K+ channels are strongly expressed in the heart and are responsible for a rapid component (IKr) of the repolarizing currents in the cardiac action potential (Curran ‘95; Sanguinetti ‘95). Loss of function mutations affecting hERG are associated with some inherited forms of long QT syndrome (LQTS) and increase the risk for a serious ventricular arrhythmia, torsade de pointes (Tanaka ‘97; Moss ‘02). HERG K+ channel inhibition by both cardiac and non cardiac drugs has also been identified as the most common cause of acquired, drug-induced LQTS that may lead to sudden cardiac death (Vandenberg, Walker & Campbell ‘01). In fact, the side effect of hERG K+ channel inhibition is one of the major reasons of drug withdrawal or drug re-labeling in recent years, therefore in vitro evaluation of the effects of drugs on hERG channels expressed heterologously in mammalian cells has been recommended as part of the preclinical safety package by the International Conference on Harmonization (ICHS7B Expert Working Group, ‘02).
The gold standard of evaluating drug effects on hERG K+ current is manual patch-clamp recording. However, this low-throughput, high-cost approach is limiting in safety screening of large numbers of drugs. Recently, automated electrophysiology systems have been developed that can obtain high-throughput recordings and achieve reasonably comparable results with manual patch clamp. The IonFluxTM system developed by Fluxion Biosciences is designed to combine the convenience and throughput of a plate reader with the performance of the traditional patch clamp assay. Here we present results of recordings of hERG currents expressed in mammalian cell cultures and the pharmacological inhibition profiles of a panel of drug compounds using the IonFlux system single cells mode. 

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