Human cardiomyocytes obtained by directed differentiation of human induced pluripotent stem cells as isoprenaline-based model to evaluate arrhythmogenicity

BACKGROUND: Human cardiomyocytes obtained by directed differentiation from induced pluripotent stem cells are a promising model for evaluating arrhythmogenicity and the electrophysiological response to beta-adrenergic stimulation. Isoprenaline is a non-selective beta-adrenergic agonist that is widely used in cardiac electrophysiology studies and clinical practice to treat bradycardia, heart block, and cardiac arrest. However, there is limited quantitative data on its effects on human cardiac ion channels because most studies are conducted on animal models under non-physiological conditions. AIM: The study aimed to evaluate the effects of isoprenaline on voltage-gated ion channels in human ventricular cardiomyocytes obtained by directed differentiation of human induced pluripotent stem cells from a healthy donor. METHODS: The patch clamp technique was used to record currents of ion channels, including fast sodium channels, L-type calcium channels, and delayed rectifier potassium channels. Human ventricular cardiomyocytes were obtained by directed differentiation of human induced pluripotent stem cells from a healthy donor. RESULTS: At a concentration of 1 μM, isoprenaline was found to significantly increase ion channel activity, including an increase in the amplitude of fast sodium currents (73%), L-type calcium currents (120%), and delayed rectifier potassium currents (98%). Additional parameters of electrophysiological activity were also obtained, providing a deeper understanding of a beta-adrenergic response in human cardiomyocytes. CONCLUSION: Human cardiomyocytes obtained by directed differentiation were assessed as a reliable model to evaluate arrhythmogenicity and responses to beta-adrenergic stimulation. These quantitative data can be used to create mathematical models of cardiac function and predict the behavior of cardiac tissue under sympathetic stimulation.