Key result
Using potassium fluoride in the internal recording solution for automated patch-clamp hERG screening significantly improved success rate and throughput without compromising data quality.
Using potassium fluoride in the internal recording solution optimizes automated patch-clamp hERG screening by increasing throughput and success rates while maintaining data quality.
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May enhance preclinical hERG assay efficiency; leaves open translation to clinical cardiac safety testing.
Blockade of the human ether-a-go-go-related gene (hERG) potassium channel, with a consequent possibility of QT prolongation and increased susceptibility to a characteristic polymorphic ventricular arrhythmia, torsade de pointes, is an important cause of withdrawal of drugs from the market. In the aftermath of recent drug withdrawals, regulatory agencies now require in vitro hERG screening of all pharmaceutical compounds that are targeted for human use. To minimize the potential for failure in later-stage drug development, many pharmaceutical and biotechnology companies have begun to use automated patch clamp systems with higher throughput than conventional manual patch-clamp techniques to conduct routine functional hERG screening during drug discovery and early development. We have optimized an automated patch-clamp hERG screening method for the PatchXpress 7000A system (Molecular Devices, Sunnyvale, CA) using potassium fluoride (KF) in the internal recording solution. In this study we show that (1) the biophysical and pharmacological properties of hERG current recorded with KF are similar to those with standard potassium chloride solutions, (2) use of KF significantly improves the success rate of hERG screening using PatchXpress without compromising data quality, and (3) utilization of KF can significantly increase the throughput of hERG screening with PatchXpress.
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Zeng et al. (2008) studied this question. Potassium fluoride (KF) in internal recording solution vs. Standard potassium chloride solutions was evaluated on Biophysical and pharmacological properties of hERG current, success rate, and throughput. Using potassium fluoride in the internal recording solution for automated patch-clamp hERG screening significantly improved success rate and throughput without compromising data quality.
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