RT Journal Article T1 Synergistic Effect of Brevetoxin BTX-3 and Ciguatoxin CTX3C in Human Voltage-Gated Nav1.6 Sodium Channels A1 Raposo García, Sandra A1 Costas Sánchez, Celia A1 Louzao Ojeda, María del Carmen A1 Rodríguez Vieytes, Mercedes A1 Vale González, María del Carmen A1 Botana López, Luis Miguel K1 Agonists K1 Genetics K1 Sodium K1 Toxicological synergy K1 Toxins AB Emerging marine biotoxins such as ciguatoxins and brevetoxins have been widely and independently studied as food pollutants. Their maximum levels in food components were set without considering their possible synergistic effects as consequence of their coexistence in seafood and their action at the same cellular target. The absolute lack of data and regulations of the possible combined effects that both marine biotoxins may have raised the need to analyze their direct in vitro effects using electrophysiology techniques. The results presented in this study indicate that ciguatoxins and brevetoxins had a synergistic effect on human Nav1.6 voltage-gated sodium channels by hyperpolarizing their activation and inactivation states. The results presented here indicate that brevetoxin 3 (BTX-3) acts as partial agonist of human sodium channels, while ciguatoxin 3C (CTX3C) was a full agonist, explaining the differences in the effect of each toxin in the channel. Therefore, this work sets the cellular basis to further apply this type of studies to other food toxicants that may act synergistically and thus implement the corresponding regulatory limits considering their coexistence and the risks to human and animal health derived from it PB American Chemical Society (ACS) SN 0893-228X YR 2023 FD 2023 LK http://hdl.handle.net/10347/33886 UL http://hdl.handle.net/10347/33886 LA eng NO Chem. Res. Toxicol. 2023, 36, 1990−2000 NO The research leading to these results has received funding from the following grants. From Campus Terra (USC), BreveRiesgo (2022-PU011) CLIMIGAL (2022- PU016). From Conselleria de Cultura, Educacion e Ordenación Universitaria, Xunta de Galicia, GRC (ED431C 2021/01). From European Union, Interreg EAPA-0032/2022─BEAP-MAR, HORIZON-MSCA-2022-DN-01-MSCA Doctoral Networks 2022 101119901-BIOTOXDoc, and HORIZON-CL6-2023-CIRCBIO-01 COMBO-101135438 DS Minerva RD 24 abr 2026