Short- and long-term effects of dronedarone on Cav3.1- and Cav3.2-T-type calcium channel current

T-type calcium channels (TTCCs), including the Cav3.1 and Cav3.2 subtypes, play a critical role in regulating cardiac electrical activity. Their abnormal expression is closely associated with arrhythmias and cardiac dysfunction caused by myocardial infarction (MI). Dronedarone, a multi-target antiarrhythmic drug, is widely used to treat atrial fibrillation and atrial flutter but has shown adverse effects under pathological conditions such as MI. This study aims to investigate the direct effects and underlying mechanisms of dronedarone on TTCCs. Using neonatal rat cardiomyocytes, HEK293T cells transfected with Cav3.1 and Cav3.2, and MI rat model, we systematically analyzed the effects of dronedarone on TTCC activity. Dronedarone significantly inhibited Cav3.2 channel activity with an IC50 of 9.20 µM, while its effect on Cav3.1 was weaker (IC50 = 46.41 µM). Chronic treatment with dronedarone also slowed the activation and inactivation kinetics of TTCCs. In vivo experiments demonstrated that dronedarone exacerbated myocardial damage and fibrosis in the MI model. These findings suggest that dronedarone inhibits TTCC activity, particularly the Cav3.2 subtype, and alters its kinetic properties. This study reported the electrophysiological effects of dronedarone on T-type calcium channels, providing new insights into its electrophysiological properties and potential role in adverse cardiac events.