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

Nat Neurosci. 2011 Apr;14(4):513-8. doi: 10.1038/nn.2776. Epub 2011 Mar 13.


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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Signaling / physiology*
  • Calcium Signaling / radiation effects
  • Cell Membrane Permeability / physiology
  • Cell Membrane Permeability / radiation effects
  • Cells, Cultured
  • Channelrhodopsins
  • Crystallography, X-Ray
  • HEK293 Cells
  • Humans
  • Light*
  • Nerve Tissue Proteins / physiology*
  • Nerve Tissue Proteins / radiation effects
  • Neurons / physiology*
  • Neurons / radiation effects
  • Oocytes / physiology
  • Oocytes / radiation effects
  • Photic Stimulation / methods
  • Rats
  • Reaction Time / physiology
  • Reaction Time / radiation effects
  • Synaptic Transmission / physiology
  • Synaptic Transmission / radiation effects
  • Xenopus laevis


  • Channelrhodopsins
  • Nerve Tissue Proteins

Associated data

  • PDB/1H2S