• CDR1as knockdown via AAV9-shRNA improves cardiac function and restores ICaL density and Cav1.2 expression in post-MI mice.
• Cav1.2 expression is significantly decreased in the infarct border zone at 12 hours post-MI, implicating calcium channel remodeling in arrhythmogenesis.
• Targeting the CDR1as pathway to modulate L-type calcium channels represents a novel antiarrhythmic strategy after myocardial infarction.
• The study provides evidence that CDR1as contributes to ventricular arrhythmias by disrupting calcium homeostasis, expanding its role beyond sodium and potassium channels.