electromechanical-assessment-optogenetically-modulated-cardiomyocyte

Electromechanical Assessment of Optogenetically Modulated Cardiomyocyte Activity

Over the past two decades, optogenetic tools have been established as potent means to modulate cell-type specific activity in excitable tissues, including ...

Medical Center-University of Freiburg

University of Freiburg

Optogenetics is an emerging, interdisciplinary research area which combines genetic and optical technologies to steer and monitor specific biological processes. To this end, light-activated proteins, so-called optogenetic actuators, or fluorescent sensor proteins are genetically targeted to the cells of interest. Light activation can then be used to modulate or record cellular behaviour with high spatiotemporal precision. In cardiac research, optogenetic approaches have been used to unravel heterocellular electrotonic interactions, both in vitro and in situ. Pioneering optogenetic studies with potential relevance for clinical electrophysiology include light-controlled pacing experiments and optical defibrillation studies. However, despite successful implementation in mouse models, clinical applications are not feasible to date; these will require major advances in gene therapy and in optical techniques.

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Optogenetics enables manipulation of biological processes with light at high spatio-temporal resolution to control the behavior of cells, networks, or even whole animals. In contrast to the performance of excitatory rhodopsins, the effectiveness of inhibitory optogenetic tools is still insufficient. Here we report a two-component optical silencer system comprising photoactivated adenylyl cyclases (PACs) and the small cyclic nucleotide-gated potassium channel SthK. Activation of this 'PAC-K' silencer by brief pulses of low-intensity blue light causes robust and reversible silencing of cardiomyocyte excitation and neuronal firing. In vivo expression of PAC-K in mouse and zebrafish neurons is well tolerated, where blue light inhibits neuronal activity and blocks motor responses. In combination with red-light absorbing channelrhodopsins, the distinct action spectra of PACs allow independent bimodal control of neuronal activity. PAC-K represents a reliable optogenetic silencer with intrinsic amplification for sustained potassium-mediated hyperpolarization, conferring high operational light sensitivity to the cells of interest.

Franziska Schneider-Warme

Institute for Experimental Cardiovascular Medicine,
University Heart Center Freiburg-Bad Krozingen,
Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg-Bad Krozingen

Medical Center-University of Freiburg

Electromechanical Assessment of Optogenetically Modulated Cardiomyocyte Activity

Franziska Schneider-Warme

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Institute for Experimental Cardiovascular Medicine,University Heart Center Freiburg-Bad Krozingen,Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg-Bad Krozingen

Medical Center-University of Freiburg

Electromechanical Assessment of Optogenetically Modulated Cardiomyocyte Activity

Institute for Experimental Cardiovascular Medicine,
University Heart Center Freiburg-Bad Krozingen,
Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg-Bad Krozingen