title: Ultra light-sensitive and fast neuronal activation with the Ca²+-permeable channelrhodopsin CatCh.
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.
authors.affiliation: Max Planck Institute of Biophysics, Department of Biophysical Chemistry, Frankfurt am Main, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kleinlogel
authors.forename: Katrin
authors.initials: K
authors.lastname: Feldbauer
authors.forename: Robert E
authors.initials: RE
authors.lastname: Dempski
authors.forename: Heike
authors.initials: H
authors.lastname: Fotis
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Wood
authors.forename: Christian
authors.initials: C
authors.lastname: Bamann
authors.forename: Ernst
authors.initials: E
authors.lastname: Bamberg
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology* / Q000528:radiation effects; D002463:Cell Membrane Permeability / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D000075402:Channelrhodopsins; D018360:Crystallography, X-Ray; D057809:HEK293 Cells; D006801:Humans; D008027:Light; D009419:Nerve Tissue Proteins / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000502:physiology* / Q000528:radiation effects; D009865:Oocytes / Q000502:physiology / Q000528:radiation effects; D010775:Photic Stimulation / Q000379:methods; D051381:Rats; D011930:Reaction Time / Q000502:physiology / Q000528:radiation effects; D009435:Synaptic Transmission / Q000502:physiology / Q000528:radiation effects; D014982:Xenopus laevis
chemical_list: D000075402:Channelrhodopsins; D009419:Nerve Tissue Proteins