CDR1as modulates arrhythmia post-myocardial infarction via regulating Cav1.2.

Arrhythmias, especially ventricular arrhythmias (VAs), are the primary cause of mortality following myocardial infarction (MI) and are typically attributable to electrophysiological disorders of the heart. Our previous work demonstrated that CDR1as knockdown ameliorates arrhythmias by modulating Nav1.5 and Kir6.2 channels post-MI. This study aims to explore the role of CDR1as in calcium channel remodeling subsequent to ischemic arrhythmia. We employ MI in mice by ligating the left anterior descending coronary artery (LAD) and use patch-clamp techniques to measure the Ca current ( I _CaL) in isolated ventricular cardiomyocytes. The results show that the expression of Cav1.2 is significantly decreased in the infarct border zone at 12 h post-MI. CDR1as knockdown via AAV9-CDR1as-shRNA administration leads to an enhancement of cardiac function and a restoration of both I _CaL density and Cav1.2 expression in MI model mice. These findings indicate that targeting the CDR1as pathway to modulate calcium channels can be a viable strategy for antiarrhythmic therapy following MI.