Synthetic Ciguatoxin CTX 3C Induces a Rapid Imbalance in Neuronal Excitability

Victor Martín, Carmen Vale, Masahiro Hirama, Shuji Yamashita, Juan Andrés Rubiolo, Mercedes R. Vieytes, Luis M. Botana

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Ciguatera is a human global disease caused by the consumption of contaminated fish that have accumulated ciguatoxins (CTXs), sodium channel activator toxins. Symptoms of ciguatera include neurological alterations such as paraesthesiae, dysaesthesiae, depression, and heightened nociperception, among others. An important issue to understand these long-term neurological alterations is to establish the role that changes in activity produced by CTX 3C represent to neurons. Here, the effects of synthetic ciguatoxin CTX 3C on membrane potential, spontaneous spiking, and properties of synaptic transmission in cultured cortical neurons of 11-18 days in vitro (DIV) were evaluated using electrophysiological approaches. CTX 3C induced a large depolarization that decreased neuronal firing and caused a rapid inward tonic current that was primarily GABAergic. Moreover, the toxin enhanced the amplitude of miniature postsynaptic inhibitory currents (mIPSCs), whereas it decreased the amplitude of miniature postsynaptic excitatory currents (mEPSCs). The frequency of mIPSCs increased, whereas the frequency of mEPSCs remained unaltered. We describe, for the first time, that a rapid membrane depolarization caused by CTX 3C in cortical neurons activates mechanisms that tend to suppress electrical activity by shifting the balance between excitatory and inhibitory synaptic transmission toward inhibition. Indeed, these results suggest that the acute effects of CTX on synaptic transmission could underlie some of the neurological symptoms caused by ciguatera in humans.

Original languageEnglish
Pages (from-to)1095-1108
Number of pages14
JournalChemical Research in Toxicology
Volume28
Issue number6
DOIs
Publication statusPublished - 2015 Jun 15

ASJC Scopus subject areas

  • Toxicology

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