Journal
SCIENCE
Volume 344, Issue 6182, Pages 409-412Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1249375
Keywords
-
Categories
Funding
- Leibniz Graduate school
- Deutsche Forschungsgemeinschaft [SFB1078, FOR1279, SPP1665]
- Grants-in-Aid for Scientific Research [14J03041] Funding Source: KAKEN
Ask authors/readers for more resources
The field of optogenetics uses channelrhodopsins (ChRs) for light-induced neuronal activation. However, optimized tools for cellular inhibition at moderate light levels are lacking. We found that replacement of E90 in the central gate of ChR with positively charged residues produces chloride-conducting ChRs (ChloCs) with only negligible cation conductance. Molecular dynamics modeling unveiled that a high-affinity Cl--binding site had been generated near the gate. Stabilizing the open state dramatically increased the operational light sensitivity of expressing cells (slow ChloC). In CA1 pyramidal cells, ChloCs completely inhibited action potentials triggered by depolarizing current injections or synaptic stimulation. Thus, by inverting the charge of the selectivity filter, we have created a class of directly light-gated anion channels that can be used to block neuronal output in a fully reversible fashion.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available