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Ultra light-sensitive and fast neuronal activation with Ca2+-permeable channelrhodopsin CatCh

14 April 2011. The light-gated cation channel channelrhodopsin-2 (ChR2) has rapidly become a very important tool in neuroscience, and its use is being considered in a number of 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. A team of scientists at the Max Planck Institute of Biophysics in Frankfurt lead by Ernst Bamberg developed 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. The results were published in the latest issue of the journal Nature Neuroscience.

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.

These 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.

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Full reference: Sonja Kleinlogel, Katrin Feldbauer, Robert E Dempski, Heike Fotis, Phillip G Wood, Christian Bamann & Ernst Bamberg. 2011. Nature Neuroscience 14, 513–518