In vivo spatiotemporal control of voltage-gated ion channels by using photoactivatable peptidic toxins

Nat Commun. 2022 Jan 20;13(1):417. doi: 10.1038/s41467-022-27974-w.

Abstract

Photoactivatable drugs targeting ligand-gated ion channels open up new opportunities for light-guided therapeutic interventions. Photoactivable toxins targeting ion channels have the potential to control excitable cell activities with low invasiveness and high spatiotemporal precision. As proof-of-concept, we develop HwTxIV-Nvoc, a UV light-cleavable and photoactivatable peptide that targets voltage-gated sodium (NaV) channels and validate its activity in vitro in HEK293 cells, ex vivo in brain slices and in vivo on mice neuromuscular junctions. We find that HwTxIV-Nvoc enables precise spatiotemporal control of neuronal NaV channel function under all conditions tested. By creating multiple photoactivatable toxins, we demonstrate the broad applicability of this toxin-photoactivation technology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / physiology
  • HEK293 Cells
  • Humans
  • Ion Channel Gating / radiation effects
  • Light*
  • Mice
  • Mice, Inbred C57BL
  • Neurons / physiology
  • Neurons / radiation effects
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / toxicity*
  • Protein Engineering
  • Time Factors
  • Toxins, Biological / toxicity*
  • Ultraviolet Rays
  • Voltage-Gated Sodium Channels / metabolism*
  • Zebrafish

Substances

  • Peptides
  • Toxins, Biological
  • Voltage-Gated Sodium Channels