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Optogenetic Control of Heterocellular Contributions to Cardiac Excitation and Arrhythmogenesis (C13 (P13))

Subject Area Anatomy and Physiology
Biochemistry
Cardiology, Angiology
Term since 2020
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 422681845
 
Using BiPOLES (optogenetic tools for bi-directional control of electrical cell polarisation), we will assess the effects of cyclic membrane de- and repolarisation of non-myocytes on their structure and function. Such dynamic changes would be experienced by non-myocytes that are electrotonically coupled to adjacent cardiomyocytes, and the consequences of such rhythmic membrane potential changes for non-myocytes are unknown. We will also dissect contributions of non-myocytes to cardiac electrophysiology, comparing young, aged and lesioned mouse hearts following transverse aortic constriction surgery. Using light-gated K+ channels and blue light-inducible gene expression tools that we established in the first funding period, we will assess how hyperpolarising currents elicited in either fibroblasts or macrophages will modulate tissue excitability and arrhythmogenesis in native and lesioned myocardium. We will test whether such currents can be used to terminate ventricular tachyarrhythmias. Finally, in order to simplify and/ or expand the use of optogenetic manipulation of gene expression in whole hearts (initially ex vivo, but in the longer term in living animals too), we will develop tools for red light-activatable control of gene expression in deep tissue, paving the way to non-invasive modulation of scar properties in a cell type-specific and spatio-temporally controlled manner.
DFG Programme Collaborative Research Centres
Applicant Institution Albert-Ludwigs-Universität Freiburg
 
 

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