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Ultra light-sensitive and fast neuronal activation with the Ca²+-permeable channelrhodopsin CatCh.
Kleinlogel S
,
Feldbauer K
,
Dempski RE
,
Fotis H
,
Wood PG
,
Bamann C
,
Bamberg E
.
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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.
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