Human TRPV1 Channels are Functional Allosteric Receptors for Ciguatoxins and Brevetoxins

Ciguatera poisoning (CP) is a foodborne illness caused by the consumption of seafood containing ciguatoxins (CTXs). There is a wide variety of symptoms associated with ciguatera poisoning; however, the origin and physiological cause of many of them remains still unclear. Although the primary effect of ciguatoxins and brevetoxins (BTX) is their effect in voltage-gated sodium channels, in this work, the effect of both toxins on human transient receptor potential vanilloid 1 (TRPV1) channels was investigated under different physiological conditions that may contribute to CP. The results obtained showed that different physiological conditions that may occur in the organism potentiated the effect of ciguatoxins on TRPV1. Among these conditions, low pH, the presence of oxidative stress products, or endogenous ligands increased the TRPV1 currents induced by CTX3C and hyperpolarized their activation voltage. In addition, neurotoxic shellfish poisoning symptomatology (NSP), caused by brevetoxins, was previously linked to TRPV1 channels; therefore, in this study brevetoxins and ciguatoxins were combined to evaluate their effects on TRPV1 channels. The results obtained demonstrated that brevetoxin 3 alone did not alter TRPV1 channel currents or their activation; however, in the presence of the endogenous ligand anandamide BTX3 effects were potentiated. Furthermore, an allosteric effect of ciguatoxins and brevetoxins was observed, since the simultaneous presence of 0.5 nM CTX3C with different concentrations of BTX activated TRPV1 channels, increasing their maximum current intensity and hyperpolarizing the activation voltage.