Ultra light-sensitive and fast neuronal activation with the Ca-permeable Channelrhodopsin CatCh

Sonja Kleinlogel (1) , Katrin Feldbauer (1) , Robert Edward Dempski (1) , Heike Fotis (1) , Phillip G Wood (1) , Christian Bamann (1) , Ernst Bamberg (1)

1 Biophysical Chemistry

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.

Mots clés: Channels; Technical report; Neurophysiology

Sonja Kleinlogel, Katrin Feldbauer, Robert Edward Dempski, Heike Fotis, Phillip G Wood, et al.. Ultra light-sensitive and fast neuronal activation with the Ca-permeable Channelrhodopsin CatCh. Nature Neuroscience, 2011, ⟨10.1038/nn.2776⟩. ⟨hal-00622878⟩