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2022 - In vivo spatiotemporal control of voltage-gated ion channels by using photoactivatable peptidic toxins

icon sp96  SyncroPatch 384PE (a predecessor model of the SyncroPatch 384 instrument) Publication in Nature Communications (2022)

Authors:
Montnach J., Blömer L. A., Lopez L., Filipis F., Meudal H., Lafoux A., Nicolas S., Chu D., Caumes C., Béroud R., Jopling C., Bosmans F., Huchet C., Landon C., Canepari M., De Waard M.

Journal:
Nature Communications (2022) 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.


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