Conversion of channelrhodopsin into a light-gated chloride channel.
Science
; 344(6182): 409-12, 2014 Apr 25.
Article
em En
| MEDLINE
| ID: mdl-24674867
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rodopsina
/
Cloretos
/
Canais de Cloreto
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha