RT Journal Article
T1 Differential effects of ciguatoxin and maitotoxin in primary cultures of cortical neurons
A1 Martín, Víctor
A1 Vale González, María del Carmen
A1 Antelo, Álvaro
A1 Hirama, Masahiro
A1 Yamashita, Shuji
A1 Rodríguez Vieytes, Mercedes
A1 Botana López, Luis Miguel
K1 Ciguatoxi
K1 CTX 3C
K1 Maitotoxin
K1 Voltage-gated channel
K1 Cortical neuron
K1 Cytosolic calcium concentration
K1 Intracellular pH
K1 Neurotoxicity
AB Ciguatoxins (CTXs) and maitotoxins (MTXs) are polyether ladder shaped toxins derived from the dinoflagellate Gambierdiscus toxicus. Despite the fact that MTXs are 3 times larger than CTXs, part of the structure of MTXs resembles that of CTXs. To date, the synthetic ciguatoxin, CTX 3C has been reported to activate voltage-gated sodium channels, whereas the main effect of MTX is inducing calcium influx into the cell leading to cell death. However, there is a lack of information regarding the effects of these toxins in a common cellular model. Here, in order to have an overview of the main effects of these toxins in mice cortical neurons, we examined the effects of MTX and the synthetic ciguatoxin CTX 3C on the main voltage dependent ion channels in neurons, sodium, potassium, and calcium channels as well as on membrane potential, cytosolic calcium concentration ([Ca(2+)]c), intracellular pH (pHi), and neuronal viability. Regarding voltage-gated ion channels, neither CTX 3C nor MTX affected voltage-gated calcium or potassium channels, but while CTX 3C had a large effect on voltage-gated sodium channels (VGSC) by shifting the activation and inactivation curves to more hyperpolarized potentials and decreasing peak sodium channel amplitude, MTX, at 5 nM, had no effect on VGSC activation and inactivation but decreased peak sodium current amplitude. Other major differences between both toxins were the massive calcium influx and intracellular acidification produced by MTX but not by CTX 3C. Indeed, the novel finding that MTX produces acidosis supports a pathway recently described in which MTX produces calcium influx via the sodium-hydrogen exchanger (NHX). For the first time, we found that VGSC blockers partially blocked the MTX-induced calcium influx, intracellular acidification, and protected against the short-term MTX-induced cytotoxicity. The results presented here provide the first report that shows the comparative effects of two prototypical ciguatera toxins, CTX 3C and MTX, in a neuronal model. We hypothesize that the analogies and differences in the bioactivity of these two toxins, produced by the same microorganism, may be strongly linked to their chemical structure.
PB American Chemical Society
YR 2014
FD 2014-07-07
LK https://hdl.handle.net/10347/47269
UL https://hdl.handle.net/10347/47269
LA eng
NO Differential Effects of Ciguatoxin and Maitotoxin in Primary Cultures of Cortical Neurons Victor Martin, Carmen Vale, Alvaro Antelo, Masahiro Hirama, Shuji Yamashita, Mercedes R. Vieytes, and Luis M. Botana Chemical Research in Toxicology 2014 27 (8), 1387-1400 DOI: 10.1021/tx5000969
NO This document is the Accepted Manuscript version of a Published Article that appeared in final form in Chemical Research in Toxicology, copyright © 2014 American Chemical Society. To access the final published article, see https://doi.org/10.1021/tx5000969
DS Minerva
RD 21 may 2026