The voltage-gated sodium channels Nav1.7, Nav1.8, and Nav1.9 drive action potentials in nociceptors, with Nav1.9 regulating firing thresholds. There is a significant need for new chronic pain treatments due to the limitations of existing analgesics. While Nav1.7 and Nav1.8 have been widely explored, Nav1.9 is an attractive pain target due to its nociceptor-specific expression and genetic link to pain insensitivity. However, its prosecution has been challenging due to expression difficulties in heterologous systems.
Metrion has developed a monoclonal CHO cell line expressing hNav1.9, validated via manual and automated patch clamp techniques. Using Qube384, we established a high-throughput Nav1.9 assay, recording stable currents with GTPγS and multi-hole acquisition. The sodium channel inhibitor TC-N 1752 showed concentration-dependent inhibition (IC50 0.45 µM). Our robust high-throughput electrophysiology assay provides a reliable platform for Nav1.9 drug discovery.
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.