Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 409-412 |
| Number of pages | 4 |
| Journal | Science |
| Volume | 344 |
| Issue number | 6182 |
| DOIs | |
| Publication status | Published - 2014 Jan 1 |
| Externally published | Yes |
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ASJC Scopus subject areas
- General
- Medicine(all)
- History and Philosophy of Science
Cite this
Conversion of channelrhodopsin into a light-gated chloride channel. / Wietek, Jonas; Wiegert, J. Simon; Adeishvili, Nona; Schneider, Franziska; Watanabe, Hiroshi; Tsunoda, Satoshi P.; Vogt, Arend; Elstner, Marcus; Oertner, Thomas G.; Hegemann, Peter.
In: Science, Vol. 344, No. 6182, 01.01.2014, p. 409-412.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Conversion of channelrhodopsin into a light-gated chloride channel
AU - Wietek, Jonas
AU - Wiegert, J. Simon
AU - Adeishvili, Nona
AU - Schneider, Franziska
AU - Watanabe, Hiroshi
AU - Tsunoda, Satoshi P.
AU - Vogt, Arend
AU - Elstner, Marcus
AU - Oertner, Thomas G.
AU - Hegemann, Peter
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84899629429&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899629429&partnerID=8YFLogxK
U2 - 10.1126/science.1249375
DO - 10.1126/science.1249375
M3 - Article
C2 - 24674867
AN - SCOPUS:84899629429
VL - 344
SP - 409
EP - 412
JO - Science
JF - Science
SN - 0036-8075
IS - 6182
ER -