Tetrodotoxin

Title

It kills in hours, and it does so by exploiting your own nervous system. By weight, it’s 10,000 times deadlier than cyanide.  It leaves you zombified and helpless yet conscious as you meet whatever deity you believe awaits you in the afterlife. This death, dear readers, is the result of consuming tetrodotoxin.

You may have heard of a Japanese dish called fugu. In Japanese, fugu refers to both pufferfish and the dish that is prepared using it. Pufferfish harbor the growth of symbiotic toxin-producing bacteria (remember mutualism?) in exchange for the extremely potent tetrodotoxin (called TTX), which acts as a defense against nearly all natural predators. Several important parts of the fish contain the toxin, including the eyes, ovaries, and liver of the fish. In Japan and throughout the world, Fugu is a culinary rite of passage of sorts, tempting risk-takers and novelty-seekers with the deliciousness of the dish and the intriguing oral numbness that comes along. The dish apparently also gets people high, which is pretty strange. Many also consider it one of the world’s tastiest fish. Sounds awesome, where can I pay money for some?

Fugu can also kill the shit out of you, which kinda sucks.

How? Stand back as I attempt to summarize how your nervous system works in a single paragraph using words any 5-year old could understand. Ahem.

Every single nervous system on the planet, from tiny fruit fly brains to our mondo-sized noggins, works exactly the same at the level of the cell. The workhorses of nervous tissues are cells called neurons that send one-directional signals, called action potentials, to other neurons. In a way, these cells talk to each other using electrical signals. Neurons become electrically excited on one end of the cell, but they have to transfer it to a completely different part of the cell in order to send the signal to the next neuron in the line. These signals move from one end to the other by opening ion channels, little gates in the cell membrane that allow tiny charged ions to move in or out of the cell. Sodium and potassium are the two most important ions in this process, so neurons have sodium channels and potassium channels that allow only those ions to pass through. Without these ion channels, the neuron cannot move ions and change its charge, making it impossible to talk to the next neuron in the circuit. Click here for a more visual explanation of how this works.

How does tetrodotoxin kill you to death? It simply clogs sodium channels. There’s a site on the sodium channel where tetrodotoxin sticks, and it sticks there freakishly strong. Because of that, tetrodotoxin hangs out and screws shit up for a really really long time. While similar toxins interact with sodium channels on the nanosecond scale (one billionth of a second), tetrodotoxin can stick to a single ion channel for f**king tens of seconds. THAT’S AT LEAST 100 MILLION TIMES AS LONG.

If I were tetrodotoxin, I’d be all over that sexy-looking voltage-gated sodium channel. Just look at dat TTX binding site. MMMMMMmmmm.

With no sodium passing through the channel, the neuron cannot generate an action potential. Not having neurons communicate can be pretty harmless sometimes, producing numbness or dizziness if the number of affected neurons is small. Plus, blocked channels don’t cause the neuron any harm, so it’s not like the toxin is killing nerve cells after it wears off. So what’s the deal, why is this toxin so fatal?

Well, the earth seems to have gotten pretty good at killing us. Most deaths today are due to conditions that attack two of our most important organs: the heart and lungs. In 2012, heart disease, stroke, COPD, lower respiratory infections, and lung cancers were the top 5 causes of death worldwide, totaling 21.9 million fatalities. This is not a small number. In fact, these five diseases alone are responsible for almost 2 of every 5 deaths.

If you were  trying to design a toxin that could kill large mammals like ourselves, you’d be right to target the heart, lungs, and anything necessary to make those work properly. You know how breathing requires you to move your diaphragm to suck in air and blow it out? Try it now, breathe without moving your diaphragm. If you think it’s impossible, you’d be right. If you aren’t moving your diaphragm and have not been for a long while, please call an ambulance. You have likely died.

Tetrodotoxin works so beautifully (for organisms that defend themselves with it, that is) because it shuts down our ability to control the muscles that move air into and out of our lungs. Without those, we suffocate to death, slowly and consciously. Nope. No, no way, no thank you, I’m out, screw that, better luck next time slugheads.

This is a particularly nasty death. Symptoms of toxicity begin with facial numbness, followed by facial paralysis. Then, gradually, the rest of the body goes numb, but not until after convulsions, loss of speech, respiratory and cardiac arrhythmia, and severe mental impairment occur. Then, fully-body paralysis results in either asphyxiation or cardiac arrest, during which patients are lucid or have only until recently lost consciousness.

How much toxin does it take to induce this? About 1/1500th of a teaspoon. Just one friggin milligram.

Fear tetrodotoxin. Fear it with every sodium channel you have.

For further reading:
http://www.chm.bris.ac.uk/motm/ttx/ttxv.htm
http://io9.com/5879406/how-the-puffer-fish-gets-you-high-zombifies-you-and-kills-you
Image credits:
http://i.telegraph.co.uk/multimedia/archive/01803/fish_1803259c.jppg
http://www.ch.ic.ac.uk/local/projects/quek/alfasub.jppg

One response to “Tetrodotoxin

  1. Pingback: Cone Snails: The reason why I won’t be sleeping tonight | Badass Biology

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