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Potassium channel-based optogenetic silencing

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Item Type:Article
Title:Potassium channel-based optogenetic silencing
Creators Name:Bernal Sierra, Y.A., Rost, B.R., Pofahl, M., Fernandes, A.M., Kopton, R.A., Moser, S., Holtkamp, D., Masala, N., Beed, P., Tukker, J.J., Oldani, S., Bönigk, W., Kohl, P., Baier, H., Schneider-Warme, F., Hegemann, P., Beck, H., Seifert, R. and Schmitz, D.
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.
Keywords:Adenylyl Cyclases, Animal Models, Cardiac Myocytes, Channelrhodopsins, Gene Expression, Genetically Modified Animals, HEK293 Cells, Light, Neurons, Optogenetics, Potassium Channels, Rhodopsin, Transcriptional Silencer Elements, Animals, Mice, Zebrafish
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:4611
Date:5 November 2018
Official Publication:https://doi.org/10.1038/s41467-018-07038-8
PubMed:View item in PubMed

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