We report the development and optimisation of a TREK-1 functional assay using the Qube 384, an automated patch clamp platform capable of supporting high-throughput screening. The assay was optimized to identify both activators and inhibitors on the same plate, providing key mechanistic data for high value, limited supply screening libraries such as venom fractions used in this study (Targeted Venom Discovery Array, TVDA, Venomtech, UK).
Current clamp recordings provide more physiologically relevant measurements of ion channel activity (in comparison to voltage clamp), allowing the contribution of different ion channel sub-types to resting membrane potential to be evaluated.
One aim of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative is to improve drug safety testing in pre-clinical development by evaluating the proarrhythmic risk of a compound. Validation studies confirm that testing the effect of compounds on an increased number of human cardiac ion channel currents including INa (NaV1.5 peak and late current) as well as IKr (hERG) leads to improved prediction of their clinical risk.
To meet the FDA’s CiPA requirements for improved in silico action potential modelling and arrhythmia prediction, we have successfully created and implemented the challenging Milnes hERG cardiac safety assay
Rapidly activating and desensitising ligand-gated ion channel receptors can provide a technical challenge on automated patch clamp electrophysiology platforms. This can affect their biophysics, pharmacology and assay reliability. We present data on an optimised and validated acid-activated receptor assay on the QPatch that is stable enough for drug discovery screening.
As an alternative to standard pharmacological procedures for NaV1.5(Late) assays, we present a more reliable and accurate NaV1.5(Late) assay on QPatch that removes the requirement for activators like veratridine and ATX-II and delivers improved cardiac safety screening reliability and cost.
Metrion Biosciences independent analysis of the spontaneous and pacing stability of vCor.4UTM and their predictive response to selective pharmacological agents.