Ventricular arrhythmias, which have a high risk of resulting in sudden cardiac death, can be due to structural remodeling after myocardial infarction, ion channel imbalances as well as hereditary mutations. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac arrhythmia disease caused by mutations in the ryanodine receptor or the sarcoplasmic reticulum (SR) protein calsequestrin (Casq2). In CPVT, b-adrenergic Gs-stimulation promotes premature ventricular contractions (PVC) and ventricular tachycardia (VT) by enhancing SR Ca2+ leak during diastole in ventricular cardiomyocytes. b-adrenergic stimulation of the sinus node, however, may act protective by accelerating the heart rate and thus counteracting the development of PVC because of shorter diastolic intervals. In order to investigate the localized effect of β-adrenergic signaling on heart function and arrhythmia generation and to distinguish between regional specific protective and adverse effects of a high adrenergic tone, we developed a mouse model expressing Jellyfish opsin (JellyOP), a light-sensitive Gs-coupled receptor from box jellyfish, in cardiomyocytes. Illumination of isolated atrial tissue resulted in an increase of cAMP levels similar to application of isoprenaline. In Langendorff-perfused JellyOP hearts, sustained supramaximal illumination of the dorsal right atrium led to an acceleration of heart rate with a maximal increase of +44.0±9.3% (n=5), which was slightly lower than perfusion with 1 µM isoprenaline (+58.7±10.2%). However, the maximal effect on heart rate after start and wash-out after end of stimulation were much faster using JellyOP stimulation than isoprenaline application. Illumination of isolated JellyOP ventricular cardiomyocytes resulted in an instantaneous increase in the L-type Ca2+ current by +20.5±5.4% (n=8) and to a maximal increase in contractility by +218±70% (n=10). To investigate local effects of Gs-signaling on PVC and VT in a CPVT model, we crossed the JellyOP mouse line with a CPVT mouse line with heterozygous deletion in the Casq2 gene (JellyOP x Casq +/-). Upon atrial illumination we observed junctional arrhythmia in 80% of JellyOP x Casq +/- mice (n=5) but never in JellyOP x Casq +/+ mice (n=4). This type of arrhythmia was characterized by accelerated heart rates with regular narrow-shaped QRS complexes but without properly timed prior p-waves. This indicates that Casq2 heterozygous knockout might sensitize pacemaking mechanisms towards adrenergic stimulation specifically in the AV node or the ventricular conduction system. Unfortunately, we never observed the expected PVC or VT induction upon ventricular illumination of JellyOP x Casq +/- mice (n=5). Thus, next experiments will be performed on homozygous Casq2 knockout mice, which are reported to display a stronger CPVT phenotype.