Biophysical and pharmacological characterization of multiple Nav subtypes on Qube

Author(s): Anders Lindqvist, Søren Friis, Mette T. Christensen & Mads P.G. Korsgaard

The voltage dependent sodium channel is responsible for the upstroke and directed propagation of action potentials in nerve and muscle cells and is therefore a central ion channel in excitable tissues. The implication of voltage gated sodium channels in pain mediation and diseases such as epilepsy and cardiac arrhythmia has made them very important targets for drug discovery. Here we show eight subtypes of the voltage gated sodium channel tested in parallel on Qube, the Sophion 384-format automated patch clamp system designed for high throughput and high fidelity electrophysiological recordings. On Qube it is possible to run up to 16 different clones or cell lines simultaneously which ensures identical conditions across the experiments. Three types of experiments were designed to explore 1) TTX sensitivity, 2) IV-relationship for activation and inactivation and 3) pulse train suitable for screening for use dependent sodium channels blockers. For the screening example pharmacology was represented by tetracaine. For every run Nav channel subtypes Nav1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7 and 1.8 were tested side by side.