Potassium channel-based optogenetic silencing

Yinth Andrea Bernal Sierra, Benjamin R. Rost, Martin Pofahl, António Miguel Fernandes, Ramona A. Kopton, Sylvain Moser, Dominik Holtkamp, Nicola Masala, Prateep Beed, John J. Tukker, Silvia Oldani, Wolfgang Bönigk, Peter Kohl, Herwig Baier, Franziska Schneider-Warme, Peter Hegemann, Heinz Beck, Reinhard Seifert () and Dietmar Schmitz ()
Additional contact information
Yinth Andrea Bernal Sierra: Humboldt-Universität zu Berlin
Benjamin R. Rost: Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Neuroscience Research Center
Martin Pofahl: University of Bonn Medical Center
António Miguel Fernandes: Max Planck Institute of Neurobiology
Ramona A. Kopton: University Heart Center, Medical Center – University of Freiburg, and Faculty of Medicine, University of Freiburg
Sylvain Moser: Max Planck Institute of Neurobiology
Dominik Holtkamp: University of Bonn Medical Center
Nicola Masala: University of Bonn Medical Center
Prateep Beed: Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Neuroscience Research Center
John J. Tukker: Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Neuroscience Research Center
Silvia Oldani: Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Neuroscience Research Center
Wolfgang Bönigk: Center of Advanced European Studies and Research (caesar)
Peter Kohl: University Heart Center, Medical Center – University of Freiburg, and Faculty of Medicine, University of Freiburg
Herwig Baier: Max Planck Institute of Neurobiology
Franziska Schneider-Warme: University Heart Center, Medical Center – University of Freiburg, and Faculty of Medicine, University of Freiburg
Peter Hegemann: Humboldt-Universität zu Berlin
Heinz Beck: University of Bonn Medical Center
Reinhard Seifert: Center of Advanced European Studies and Research (caesar)
Dietmar Schmitz: Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Neuroscience Research Center

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-07038-8

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