Report

Conversion of Channelrhodopsin into a Light-Gated Chloride Channel

Science  27 Mar 2014:

DOI: 10.1126/science.1249375

You are currently viewing the abstract.

View Full Text

Via your Institution

Log in through your institution

Log in through your institution


Abstract

The field of optogenetics utilizes channelrhodopsins (ChRs) for light-induced neuronal activation. Optimized tools for cellular inhibition at moderate light levels are however 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.

View Full Text