A light-gated potassium channel for sustained neuronal inhibition

Laura Alberio, Andrea Locarno, Andrea Saponaro, Edoardo Romano, Valérie Bercier, Shahad Albadri, Federica Simeoni, Silvia Moleri, Silvia Pelucchi, Alessandro Porro, Elena Marcello, Noemi Barsotti, Kerri Kukovetz, Arjen J. Boender, Andrea Contestabile, Shizhen Luo, Aubin Moutal, Yingshi Ji, Giulia Romani, Monica BeltrameFilippo Del Bene, Monica Di Luca, Rajesh Khanna, Henry M. Colecraft, Massimo Pasqualetti, Gerhard Thiel, Raffaella Tonini, Anna Moroni

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)969-976
Number of pages8
JournalNature Methods
Volume15
Issue number11
DOIs
StatePublished - Nov 1 2018

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    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., ... Moroni, A. (2018). A light-gated potassium channel for sustained neuronal inhibition. Nature Methods, 15(11), 969-976. https://doi.org/10.1038/s41592-018-0186-9