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ABSTRACT The light-gated cation channel channelrhodopsin-2 (ChR2) has rapidly become an important tool in neuroscience, and its use is being considered in therapeutic interventions. Although

wild-type and known variant ChR2s are able to drive light-activated spike trains, their use in potential clinical applications is limited by either low light sensitivity or slow channel

kinetics. We present a new variant, calcium translocating channelrhodopsin (CatCh), which mediates an accelerated response time and a voltage response that is ∼70-fold more light sensitive

than that of wild-type ChR2. CatCh's superior properties stem from its enhanced Ca2+ permeability. An increase in [Ca2+]i elevates the internal surface potential, facilitating

activation of voltage-gated Na+ channels and indirectly increasing light sensitivity. Repolarization following light-stimulation is markedly accelerated by Ca2+-dependent BK channel

activation. Our results demonstrate a previously unknown principle: shifting permeability from monovalent to divalent cations to increase sensitivity without compromising fast kinetics of

neuronal activation. This paves the way for clinical use of light-gated channels. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS KALIUM CHANNELRHODOPSINS ARE NATURAL LIGHT-GATED POTASSIUM

CHANNELS THAT MEDIATE OPTOGENETIC INHIBITION Article 20 June 2022 CALCIUM-PERMEABLE CHANNELRHODOPSINS FOR THE PHOTOCONTROL OF CALCIUM SIGNALLING Article Open access 21 December 2022 SPECIFIC

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PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS We would like to thank I. Bartnik for the preparation of the hippocampal neuron cultures, S. O'Shea for the help with the

calcium imaging experiments, V. Busskamp for the support in recombinant adeno-associated virus construction, H. Biehl for excellent technical assistance, and K. Hartung, H. Spors, U. Terpitz

and M. van Wyk for helpful discussions. The work was supported by grants from the Deutsche Forschungsgemeinschaft Sonderforschungsbereich 807, Centre of Excellence Frankfurt Macromolecular

Complexes and the Federal Ministry of Education and Research of Germany (01GQ0815) to E.B., and by the Max Planck Society. AUTHOR INFORMATION Author notes * Robert E Dempski Present address:

Present address: Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, Massachusetts, USA., * Katrin Feldbauer and Robert E Dempski: These authors

contributed equally to this work. AUTHORS AND AFFILIATIONS * Department of Biophysical Chemistry, Max Planck Institute of Biophysics, Frankfurt am Main, Germany Sonja Kleinlogel, Katrin

Feldbauer, Robert E Dempski, Heike Fotis, Phillip G Wood, Christian Bamann & Ernst Bamberg * Chemical and Pharmaceutical Sciences Department, Johann-Wolfgang-Goethe-University, Frankfurt

am Main, Germany Ernst Bamberg Authors * Sonja Kleinlogel View author publications You can also search for this author inPubMed Google Scholar * Katrin Feldbauer View author publications

You can also search for this author inPubMed Google Scholar * Robert E Dempski View author publications You can also search for this author inPubMed Google Scholar * Heike Fotis View author

publications You can also search for this author inPubMed Google Scholar * Phillip G Wood View author publications You can also search for this author inPubMed Google Scholar * Christian

Bamann View author publications You can also search for this author inPubMed Google Scholar * Ernst Bamberg View author publications You can also search for this author inPubMed Google

Scholar CONTRIBUTIONS S.K., R.E.D., P.G.W. and E.B. conceived the experiments. S.K., K.F., H.F. and C.B. carried out the experiments. S.K., C.B. and K.F. performed the data analysis. S.K.,

C.B. and E.B. wrote the manuscript. CORRESPONDING AUTHOR Correspondence to Ernst Bamberg. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests.

SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–3, Supplementary Note and Supplementary Discussion (PDF 251 kb) RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kleinlogel, S., Feldbauer, K., Dempski, R. _et al._ Ultra light-sensitive and fast neuronal activation with the Ca2+-permeable

channelrhodopsin CatCh. _Nat Neurosci_ 14, 513–518 (2011). https://doi.org/10.1038/nn.2776 Download citation * Received: 19 August 2010 * Accepted: 02 February 2011 * Published: 13 March

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