A light-gated potassium channel for sustained neuronal inhibition

Nat Methods. 2018 Nov;15(11):969-976. doi: 10.1038/s41592-018-0186-9. Epub 2018 Oct 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials*
  • Animals
  • Female
  • Hyperalgesia / physiopathology*
  • Light
  • Male
  • Mice, Inbred C57BL
  • Neurons / cytology
  • Neurons / physiology*
  • Optogenetics*
  • Paclitaxel / toxicity
  • Pain / chemically induced
  • Pain / physiopathology*
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Zebrafish

Substances

  • Recombinant Fusion Proteins
  • blue-light-induced K channel 1
  • Paclitaxel

Supplementary concepts

  • Neuropathy, Painful