Chang Liao, Mei-Ling and de Boer, Teun P. and Mutoh, Hiroki and Raad, Nour and Richter, Claudia and Wagner, Eva and Downie, Bryan R. and Unsoeld, Bernhard and Arooj, Iqra and Streckfuss-Boemeke, Katrin and Doeker, Stephan and Luther, Stefan and Guan, Kaomei and Wagner, Stefan and Lehnart, Stephan E. and Maier, Lars S. and Stuehmer, Walter and Wettwer, Erich and van Veen, Toon and Morlock, Michael M. and Knoepfel, Thomas and Zimmermann, Wolfram-Hubertus (2015) Sensing Cardiac Electrical Activity With a Cardiac Myocyte-Targeted Optogenetic Voltage Indicator. CIRCULATION RESEARCH, 117 (5). pp. 401-412. ISSN 0009-7330, 1524-4571
Full text not available from this repository. (Request a copy)Abstract
Rationale: Monitoring and controlling cardiac myocyte activity with optogenetic tools offer exciting possibilities for fundamental and translational cardiovascular research. Genetically encoded voltage indicators may be particularly attractive for minimal invasive and repeated assessments of cardiac excitation from the cellular to the whole heart level. Objective: To test the hypothesis that cardiac myocyte-targeted voltage-sensitive fluorescence protein 2.3 (VSFP2.3) can be exploited as optogenetic tool for the monitoring of electric activity in isolated cardiac myocytes and the whole heart as well as function and maturity in induced pluripotent stem cell-derived cardiac myocytes. Methods and Results: We first generated mice with cardiac myocyte-restricted expression of VSFP2.3 and demonstrated distinct localization of VSFP2.3 at the t-tubulus/junctional sarcoplasmic reticulum microdomain without any signs for associated pathologies (assessed by echocardiography, RNA-sequencing, and patch clamping). Optically recorded VSFP2.3 signals correlated well with membrane voltage measured simultaneously by patch clamping. The use of VSFP2.3 for human action potential recordings was confirmed by simulation of immature and mature action potentials in murine VSFP2.3 cardiac myocytes. Optical cardiograms could be monitored in whole hearts ex vivo and minimally invasively in vivo via fiber optics at physiological heart rate (10 Hz) and under pacing-induced arrhythmia. Finally, we reprogrammed tail-tip fibroblasts from transgenic mice and used the VSFP2.3 sensor for benchmarking functional and structural maturation in induced pluripotent stem cell-derived cardiac myocytes. Conclusions: We introduce a novel transgenic voltage-sensor model as a new method in cardiovascular research and provide proof of concept for its use in optogenetic sensing of physiological and pathological excitation in mature and immature cardiac myocytes in vitro and in vivo.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CELL-DERIVED CARDIOMYOCYTES; EMBRYONIC STEM-CELLS; SENSITIVE FLUORESCENT PROTEINS; SHOCK-INDUCED ARRHYTHMOGENESIS; ISOLATED RABBIT HEART; CYTOCHALASIN-D; 2,3-BUTANEDIONE MONOXIME; OPTICAL PROBE; IN-VIVO; BLEBBISTATIN; arrhythmias; cardiac; electrophysiology; heart; myocytes; cardiac; optical imaging; optogenetics; stem cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Jun 2019 11:06 |
| Last Modified: | 14 Jun 2019 11:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5018 |
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