Dronedarone inhibits T-type calcium channel activity, particularly the Cav3.2 subtype, alters its kinetic properties, and exacerbated myocardial damage and fibrosis in a rat myocardial infarction model.
Dronedarone inhibited Cav3.2 T-type calcium channel current more potently than Cav3.1.
Chronic dronedarone treatment slowed the activation and inactivation kinetics of T-type calcium channels.
Dronedarone exacerbated myocardial damage and fibrosis in a rat myocardial infarction model.
The study provides direct electrophysiological evidence of dronedarone's effects on T-type calcium channels across several experimental systems.
Dronedarone is a heart rhythm drug used for atrial fibrillation and atrial flutter. It has been linked to harmful effects in people with heart damage, such as after a heart attack. This study examined whether the drug acts on T-type calcium channels, which are tiny gateways in heart cells that help control electrical activity and are changed after a heart attack. Using rat heart cells, human kidney-derived cells engineered to carry specific channel types, and a rat heart attack model, the researchers found that dronedarone blocked both channel subtypes tested. It was stronger against Cav3.2 (IC50 9.20 µM) than Cav3.1 (IC50 46.41 µM). Longer-term exposure also slowed how the channels open and close. In rats with induced heart attacks, dronedarone worsened heart muscle damage and scarring (fibrosis). This research suggests that blocking T-type calcium channels may help explain why dronedarone can be harmful in damaged hearts. The findings come from cell and animal experiments, so they do not by themselves show the same effects in people. They do point to a possible mechanism for further study.
Jiang X, Xu J, He H, Cao Z, Liu D, Chen Z, et al.. (2026). Short- and long-term effects of dronedarone on Cav3.1- and Cav3.2-T-type calcium channel current.. European journal of histochemistry : EJH. https://doi.org/10.4081/ejh.2026.4534