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- Title
Ultra light-sensitive and fast neuronal activation with the Ca<sup>2+</sup>-permeable channelrhodopsin CatCh.
- Authors
Kleinlogel, Sonja; Feldbauer, Katrin; Dempski, Robert E; Fotis, Heike; Wood, Phillip G; Bamann, Christian; Bamberg, Ernst
- 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.
- Publication
Nature Neuroscience, 2011, Vol 14, Issue 4, p513
- ISSN
1097-6256
- Publication type
Academic Journal
- DOI
10.1038/nn.2776