2025/10/24 by Alison Thomas, Isabella Noelle Chiong, Joana F. Neves +3 · 1 voice
Medicine · #Cardiac Arrhythmias and Treatments #Cardiac electrophysiology and arrhythmias
paper · pdf · doi:10.1101/2025.10.23.684157
openalex publication_date 2025/10/24 · openalex created_date 2025/10/25 · openalex updated_date 2026/07/14
Summary Peripheral parasympathetic ganglia lie adjacent to their target organs; their dysfunction contributes to diseases like atrial fibrillation. Due to their challenging accessibility for primary culture, we provide a step-by-step protocol to generate parasympathetic neurons from human induced pluripotent stem cells (hiPSC). They reproduce numerous native physiological features: cholinergic and autonomic markers, functional nicotinic receptors and electrophysiological properties. We also describe a co-culture system with hiPSC-atrial cardiomyocytes allowing neuromodulation of cardiomyocyte activity and offering a platform for drug discovery and disease modelling. Highlights Steps to generate parasympathetic neurons from human induced pluripotent stem cells Guidance of the functional assessment of the neurons (whole-cell patch clamp and Ca 2+ imaging) Instructions on how to co-culture these neurons with hiPSC-derived atrial cardiomyocytes Guidance of the functional assessment of the neuronal modulation of cardiomyocyte activity Graphical abstract