Ultra light-sensitive and fast neuronal activation with the Ca-permeable Channelrhodopsin CatCh
The light-gated cation channel channelrhodopsin-2 (ChR2) has rapidly become a principal tool in neuroscience and its use is currently considered in multiple therapeutic interventions. Although wild-type and known variant ChR2s are able to drive light-activated spike trains, their use in potential cl...
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Published in | Nature neuroscience |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Nature Publishing Group
01.04.2011
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Subjects | |
Online Access | Get full text |
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Summary: | The light-gated cation channel channelrhodopsin-2 (ChR2) has rapidly become a principal tool in neuroscience and its use is currently considered in multiple 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 either by low light-sensitivity or slow channel kinetics. Here we present a new variant, CatCh, mediating accelerated response time and a voltage response that is ~70-fold more light-sensitive than that of wild-type. We show that CatCh's superior properties stem from its enhanced Ca-permeability. An increase in [Ca] 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 Ca-dependent BK-channel activation. Our results demonstrate a new 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. |
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ISSN: | 1097-6256 1546-1726 |
DOI: | 10.1038/nn.2776 |