Development of a High-Throughput Automated Electrophysiology Assay for Human NaV1.9 Inhibitor Screening

Poster Description

Introduction

The voltage-gated sodium channels Na_V1.7, Na_V1.8, and Na_V1.9 drive action potentials in nociceptors, with Na_V1.9 regulating firing thresholds. There is a significant need for new chronic pain treatments due to the limitations of existing analgesics. While Na_V1.7 and Na_V1.8 have been widely explored, Na_V1.9 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 hNa_V1.9, validated via manual and automated patch clamp techniques. Using Qube384, we established a high-throughput Na_V1.9 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 Na_V1.9 drug discovery.

Download

Recommended Publications

Latest Publications

An Integrated Assay Platform for Mechanistic and Translational Profiling of Kv7.2/7.3 Activators

An integrated assay platform was developed to characterise the pharmacological and physiological effects of Kv7.2/7.3 activators. Combining high-throughput FLIPR thallium flux, automated voltage- and current-clamp electrophysiology, and sensory neuron recordings enabled assessment of compound potency, mechanism of action, and effects on neuronal resting membrane potential. Profiling of retigabine, flupirtine, ML213, ICA 069673, XEN1101 and opakalim demonstrated distinct pharmacological profiles across complementary assay systems. The workflow provides a mechanistic and translational approach for characterising Kv7.2/7.3 activators and their effects on neuronal excitability.

Action Potential Waveform Analysis in Human iPSC-Cardiomyocytes Enables Mechanistic Assessment of Multichannel Cardiac Effects

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.

View All

An Integrated Assay Platform for Mechanistic and Translational Profiling of Kv7.2/7.3 Activators

Action Potential Waveform Analysis in Human iPSC-Cardiomyocytes Enables Mechanistic Assessment of Multichannel Cardiac Effects

View All