RT Journal Article
T1 Synthetic ciguatoxin CTX 3C induces a rapid imbalance of neuronal excitability
A1 Martín, Víctor
A1 Vale González, María del Carmen
A1 Hirama, Masahiro
A1 Yamashita, Shuji
A1 Rubiolo Gaytán, Juan Andrés
A1 Rodríguez Vieytes, Mercedes
A1 Botana López, Luis Miguel
K1 Ciguatoxin
K1 Voltage gated sodium channels
K1 Depolarization
K1 Cortical neurons
K1 Synaptic transmission
K1 mEPSC
K1 mIPSC
AB 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.
PB American Chemical Society
SN 1520-5010
YR 2015
FD 2015-05-06
LK https://hdl.handle.net/10347/47338
UL https://hdl.handle.net/10347/47338
LA eng
NO Martín, V., C. Vale, et al. (2015). "Synthetic Ciguatoxin CTX 3C Induces a Rapid Imbalance in Neuronal Excitability." Chem Res Toxicol 28(6): 1095-1108.
NO This document is the Accepted Manuscript version of a Published Article that appeared in final form in Chemical Research in Toxicology, copyright  2015 American Chemical Society. To access the final published article, see https://doi.org/10.1021/tx500503d
NO The research leading to these results has received funding from the following FEDER cofunded-grants. From CDTI and Technological Funds, supported by Ministerio de Economía y Competitividad, AGL2012-40185-CO2-01 and Consellería de Cultura, Educación e Ordenación Universitaria,GRC2013-016, and through Axencia Galega de Innovación, Spain, ITC-20133020 SINTOX. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD.From the European Union’s Seventh Framework Programme managed by REA– Research Executive Agency (FP7/2007-2013) under grant agreement 312184 PHARMASEA.
DS Minerva
RD 22 may 2026