Atrial fibrillation (AF) is the most common arrhythmia observed in the clinic, considerable effort has been made to identify the cellular mechanisms of AF and develop new safe and effective antiarrhythmic drugs(1). However, preclinical studies using non-cardiac cells and non-human animal models may not replicate the physiology of human atrial cardiomyocytes or predict patient efficacy and safety.
Here we outline our results from studies to validate human induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-ACMs) generated by Axol Bioscience.
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.