Optogenetic Adrenergic Stimulation
Optogenetic stimulation of Gs signaling increases ventricular arrhythmia triggering from the endocardium and modulates arrhythmia maintenance and complexity
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 Gs-stimulation in a mouse line expressing Jellyfish opsin (JellyOp), a light-activated Gs-coupled GPCR in cardiomyocytes. This method allows for regional discrimination of adrenalin and Gs signaling effects on ventricular arrhythmia, showing that Gs 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.
Optogenetic stimulation of Gs-signaling in the heart with spatio-temporal precision
Authors: Philipp Makowka, Tobias Bruegmann, Vanessa Dusend, Daniela Malan, Thomas Beiert, Michael Hesse, Bernd K. Fleischmann, Philipp Sasse
Nat. Commun. 2019, 10: 1281
Prof. Dr. med. Philipp Sasse
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Links
- https://www.nature.com/articles/s41467-019-09322-7
- https://www.physiologie.uni-bonn.de/en/research/sasse-laboratory-physiology-i/ag-sasse