Ion channels play a key role in regulating resting membrane potential and cell excitability and are attractive targets for therapeutic intervention.
Thallium (Tl+) flux assays, which measure the flow of Tl+ through potassium channels, offer a high throughput method for the identification of potassium channel activators. However, these assays are a surrogate for channel function and it is important to have an appropriate panel of orthogonal and translational electrophysiology assays in place to confirm activity at the channel of interest.
Development of a robust hNaV1.9 high-throughput screening assay on the Sophion Qube384 platform. This is complemented by a suite of ion channel selectivity assays and sensory neuron recordings to create a versatile screening cascade to support NaV1.9 drug discovery programmes.
Optical voltage imaging of human iPSC-derived cardiomyocytes was used to assess electrophysiological effects of compounds beyond hERG inhibition. Action potential waveform analysis revealed compound-specific and concentration-dependent changes, enabling mechanistic differentiation of multichannel activity and demonstrating a human-relevant approach for translational cardiac safety assessment.