PUBLICATION
A light-gated potassium channel for sustained neuronal inhibition
- Authors
- Alberio, L., Locarno, A., Saponaro, A., Romano, E., Bercier, V., Albadri, S., Simeoni, F., Moleri, S., Pelucchi, S., Porro, A., Marcello, E., Barsotti, N., Kukovetz, K., Boender, A.J., Contestabile, A., Luo, S., Moutal, A., Ji, Y., Romani, G., Beltrame, M., Del Bene, F., Di Luca, M., Khanna, R., Colecraft, H.M., Pasqualetti, M., Thiel, G., Tonini, R., Moroni, A.
- ID
- ZDB-PUB-181101-3
- Date
- 2018
- Source
- Nature Methods 15(11): 969-976 (Journal)
- Registered Authors
- Albadri, Shahad, Beltrame, Monica, Bercier, Valérie, Del Bene, Filippo
- Keywords
- none
- MeSH Terms
-
- Hyperalgesia/physiopathology*
- Neurons/cytology
- Neurons/physiology*
- Paclitaxel/toxicity
- Animals
- Male
- Pain/chemically induced
- Pain/physiopathology*
- Mice, Inbred C57BL
- Optogenetics*
- Female
- Recombinant Fusion Proteins/genetics
- Recombinant Fusion Proteins/metabolism*
- Zebrafish
- Rats, Sprague-Dawley
- Peripheral Nervous System Diseases/chemically induced
- Peripheral Nervous System Diseases/physiopathology*
- Rats
- Light
- Action Potentials*
- PubMed
- 30377377 Full text @ Nat. Methods
Citation
Alberio, L., Locarno, A., Saponaro, A., Romano, E., Bercier, V., Albadri, S., Simeoni, F., Moleri, S., Pelucchi, S., Porro, A., Marcello, E., Barsotti, N., Kukovetz, K., Boender, A.J., Contestabile, A., Luo, S., Moutal, A., Ji, Y., Romani, G., Beltrame, M., Del Bene, F., Di Luca, M., Khanna, R., Colecraft, H.M., Pasqualetti, M., Thiel, G., Tonini, R., Moroni, A. (2018) A light-gated potassium channel for sustained neuronal inhibition. Nature Methods. 15(11):969-976.
Abstract
Currently available inhibitory optogenetic tools provide short and transient silencing of neurons, but they cannot provide long-lasting inhibition because of the requirement for high light intensities. Here we present an optimized blue-light-sensitive synthetic potassium channel, BLINK2, which showed good expression in neurons in three species. The channel is activated by illumination with low doses of blue light, and in our experiments it remained active over (tens of) minutes in the dark after the illumination was stopped. This activation caused long periods of inhibition of neuronal firing in ex vivo recordings of mouse neurons and impaired motor neuron response in zebrafish in vivo. As a proof-of-concept application, we demonstrated that in a freely moving rat model of neuropathic pain, the activation of a small number of BLINK2 channels caused a long-lasting (>30 min) reduction in pain sensation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping