Comparative Analysis of Atrial Electrophysiology Across Animal Species and Humans: Enhancing Translation in Atrial Arrhythmia Research.
Abstract
Background
Atrial arrhythmias relevantly contribute to global morbidity and death and have been extensively studied in experimental models. However, electrophysiological disparities between animal models and humans often hinder the translation of experimental findings. This study aims to systematically characterize species-specific atrial electrophysiology to improve translation.
Methods
Atrial tissue samples were obtained from patients undergoing open heart surgery and from mice, rats, pigs, and horses, and were characterized at the cellular electrophysiological and transcriptomic level using uniform protocols. To assess the correlation of functional and transcriptomic features, action potentials were simulated from ion channel expression profiles using in silico models.
Results
Porcine atrial cardiomyocytes closely resembled human cells in depolarization characteristics, whereas rodents exhibited marked differences. Human atrial action potentials showed pronounced early repolarization, which was not reproduced in other species and corresponded to a greater contribution of the IKur gene group. Late repolarization, reflected by action potential duration at 90% repolarization, scaled with species and cardiomyocyte size, with humans ranging between rodents and pigs. Sex-specific differences in repolarization observed in humans were represented in pigs but not in rodents. Chamber-specific differences between left and right atrial cardiomyocytes were reflected in in silico simulations on the basis of ion channel expression.
Conclusions
This study provides a reference for species-specific atrial action potential characteristics, linking functional properties to transcriptomic ion channel expression. It further demonstrates that relative changes in action potential parameters can be inferred from transcriptomic data using in silico simulations. These findings support more accurate interpretation and translation of animal experimental data to human atrial electrophysiology.