Optogenetic Adrenergic Stimulation

β-adrenergic activation is a major risk factor for ventricular tachycardia (VT) because it promotes calcium leak from the sarcoplasmic reticulum during diastole triggering premature ventricular contractions (PVC). This is especially exacerbated in patients after myocardial infarction or with hereditary arrhythmia such as catecholaminergic polymorphic ventricular tachycardia. Because traditional pharmacological interventions neither allow regional distinguishing nor temporally precise investigation of β-adrenergic signaling, in this project we use optogenetic G_s-stimulation in a mouse line expressing Jellyfish opsin (JellyOp), a light-activated G_s-coupled GPCR in cardiomyocytes. This method allows for regional discrimination of adrenalin and Gs signaling effects on ventricular arrhythmia, showing that G_s activation promotes triggering of VT by generating PVCs in the endocardium and furthermore, enhances inducibility and maintenance of re-entry VT and the risk of degradation into high frequency ventricular fibrillation.