Hickory dickory dock, the mouse ran up the clock... and died from MTX

Ciguatera fish poisoning is a type of poisoning associated with eating one of over 400 species of in the tropics (Caribbean and Pacific), it is caused by the bioaccumulation of ciguatoxins (CTXs) in the head, skin, viscera and roe of these fish. The toxin itself originates from the dinoflagellate Gambierdiscus toxicus, which also produces gambierol (another toxin) and the much more potent maitotoxins (MTXs). MTX is one of the most potent marine toxins known to date with an LD50 (Lethal Dose, 50% - the amount required to kill half the test population) of 0.13µg/kg (in mice), which is very potent considering the most lethal substances synthesized by humans (VX nerve agent) has a LD50 of 2.3µg/kg (in mice).

In this study by Martin et al. (2014) they look at the effects CTX and MTX have on neurons. More specifically the effect on voltage gated sodium channels (VGSC), voltage gated calcium channels (VGCC), potassium current amplitude and more. Natural MTX was used during the experiment, but CTX 3C which is a synthesized version of CTX was used instead of natural CTX. The neurons were extracted from the cerebral cortex of Swiss mice. Once the neurons were in a culture medium, a current was sent through the neurons and the toxins were added to the medium at a range of concentrations (0.001 to 1 nM for MTX and 0.01 to 10 nM for CTX).

They found that CTX effects the VGSC of cells causing hyperpolarization and increasing the activation threshold, where MTX was no significant effect on them. Neither CTX nor MTX had any effect the VGCC of the cell or on the potassium current amplitude. MTX caused an influx of cytosolic Ca²⁺, an increase in the levels of intracellular acidification and cytotoxicity eventually leading to cell death.

This shows how the different toxins effect the neurons in different ways and shows the mechanisms as to how they do this. I think it would be interesting to see this experiment repeated on the neurons of different organisms to see if they have a different effect, and to see how certain fish species are able to eat the algae that produce these toxins and instead of dying from ingesting them they accumulate them. I also wonder why organisms need to produce toxins this deadly, it isn’t a grazing deterrent as they are grazed on by fish and other algae produce compounds that make them taste bad to do that. A further understanding of these toxins would help to develop a cure for Ciguatera fish poisoning and other aliments involved with the toxins and also potential biotechnological uses for them such as medications.

Reviewed paper: Martin V., Vale C., Antelo A., Hirama M., Yamashita S., Vieytes M.R. and Botana L.M., (2014). Differential effects of ciguatoxin and maitotoxin in primary cultures of cortical neurons. Chemical research in toxicology. 27(8). pp.1387-1400.