In vivo spatiotemporal control of voltage-gated ion channels by using photoactivatable peptidic toxins.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35058427.
- Also identified by DOI 10.1038/s41467-022-27974-w and PMC identifier 8776733.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (Na<sub>V</sub>) 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 Na<sub>V</sub> channel function under all conditions tested. By creating multiple photoactivatable toxins, we demonstrate the broad applicability of this toxin-photoactivation technology.
Medical subject headings
- Light
- Peptides
- Toxins, Biological
- Voltage-Gated Sodium Channels