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Report from the 29th Meeting on Toxinology, “Toxins: From the Wild to the Lab”, Organized by the French Society of Toxinology on 30 November–1 December 2023
 
 
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Volume 16
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Article

Rattlesnake Crotalphine Analgesic Active on Tetrodotoxin-Sensitive Na+ Current in Mouse Dorsal Root Ganglion Neurons

by
Aurélie Antunes
1,2,
Philippe Robin
1,
Gilles Mourier
1,
Rémy Béroud
2,
Michel De Waard
2,3,4,
Denis Servent
1 and
Evelyne Benoit
1,*
1
Département Médicaments et Technologies pour la Santé (DMTS), Institut des Sciences du Vivant Frédéric Joliot, Université Paris-Saclay, CEA, Service d’Ingénierie Moléculaire pour la Santé (SIMoS), EMR CNRS/CEA 9004, F-91191 Gif-sur-Yvette, France
2
Smartox Biotechnology, F-38120 Saint-Egrève, France
3
L’Institut du Thorax, INSERM, CNRS, Université de Nantes, F-44007 Nantes, France
4
LabEx “Ion Channels, Science and Therapeutics”, F-06560 Valbonne, France
*
Author to whom correspondence should be addressed.
Toxins 2024, 16(8), 359; https://doi.org/10.3390/toxins16080359
Submission received: 2 July 2024 / Revised: 4 August 2024 / Accepted: 13 August 2024 / Published: 15 August 2024
(This article belongs to the Special Issue Toxins: From the Wild to the Lab)
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Abstract

Crotalphine is an analgesic peptide identified from the venom of the South American rattlesnake Crotalus durissus terrificus. Although its antinociceptive effect is well documented, its direct mechanisms of action are still unclear. The aim of the present work was to study the action of the crotalid peptide on the NaV1.7 channel subtype, a genetically validated pain target. To this purpose, the effects of crotalphine were evaluated on the NaV1.7 component of the tetrodotoxin-sensitive Na+ current in the dorsal root ganglion neurons of adult mice, using the whole-cell patch-clamp configuration, and on cell viability, using propidium iodide fluorescence and trypan blue assays. The results show that 18.7 µM of peptide inhibited 50% of the Na+ current. The blocking effect occurred without any marked change in the current activation and inactivation kinetics, but it was more important as the membrane potential was more positive. In addition, crotalphine induced an increase in the leakage current amplitude of approximately 150% and led to a maximal 31% decrease in cell viability at a high 50 µM concentration. Taken together, these results point out, for the first time, the effectiveness of crotalphine in acting on the NaV1.7 channel subtype, which may be an additional target contributing to the peptide analgesic properties and, also, although less efficiently, on a second cell plasma membrane component, leading to cell loss.
Keywords: cell viability assay; crotalphine; electrophysiology; mouse dorsal root ganglion neurons; rattlesnake toxin; tetrodotoxin-sensitive Na+ channels cell viability assay; crotalphine; electrophysiology; mouse dorsal root ganglion neurons; rattlesnake toxin; tetrodotoxin-sensitive Na+ channels

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MDPI and ACS Style

Antunes, A.; Robin, P.; Mourier, G.; Béroud, R.; De Waard, M.; Servent, D.; Benoit, E. Rattlesnake Crotalphine Analgesic Active on Tetrodotoxin-Sensitive Na+ Current in Mouse Dorsal Root Ganglion Neurons. Toxins 2024, 16, 359. https://doi.org/10.3390/toxins16080359

AMA Style

Antunes A, Robin P, Mourier G, Béroud R, De Waard M, Servent D, Benoit E. Rattlesnake Crotalphine Analgesic Active on Tetrodotoxin-Sensitive Na+ Current in Mouse Dorsal Root Ganglion Neurons. Toxins. 2024; 16(8):359. https://doi.org/10.3390/toxins16080359

Chicago/Turabian Style

Antunes, Aurélie, Philippe Robin, Gilles Mourier, Rémy Béroud, Michel De Waard, Denis Servent, and Evelyne Benoit. 2024. "Rattlesnake Crotalphine Analgesic Active on Tetrodotoxin-Sensitive Na+ Current in Mouse Dorsal Root Ganglion Neurons" Toxins 16, no. 8: 359. https://doi.org/10.3390/toxins16080359

APA Style

Antunes, A., Robin, P., Mourier, G., Béroud, R., De Waard, M., Servent, D., & Benoit, E. (2024). Rattlesnake Crotalphine Analgesic Active on Tetrodotoxin-Sensitive Na+ Current in Mouse Dorsal Root Ganglion Neurons. Toxins, 16(8), 359. https://doi.org/10.3390/toxins16080359

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