For almost every one of the key molecules involved in neuronal electrical signaling there is a naturally-occurring toxin which interferes with it. Both plants and animals have evolved these neurotoxins in response to their surroundings. Some, like those injected through the bites of poisonous snakes or spiders, function to make the animal a more effective hunter. Others work by sickening or killing animals which would prey upon them. While this might not do much good for the animal or plant which has just become lunch, it may function to protect its relatives and thereby get more of its own genes into the next generation.
Most neurotoxins work by blocking a particular molecular process in neuronal signaling: for example, many snakebite toxins work by interfering with the opening of voltage-sensitive potassium channels, thereby blocking the downstroke of the spike. Other toxins work by overactivating a key signaling event: The toxin of the black widow spider causes massive, instantaneous release of all synaptic vesicles in axon terminals, resulting in death accompanied by rigid paralysis.
The voltage-sensitive sodium channel which initiates neuronal spikes is a key target. Interfere with it and you block essentially all signaling in the brain (and the rest of the nervous system too). Sodium channel toxins have evolved independently in widely different species, but the most famous one is the toxin of the fugu, otherwise known as the Japanese pufferfish. This toxin (called tetrodotoxin) is a tiny molecular plug which fits exactly into the outer portion of the sodium channel’s central pore, thereby stopping it up. It is incredibly potent. Tetrodotoxin is more than 1,000 times as powerful as cyanide and a single pufferfish has enough to kill 30 people. While all tissues of the pufferfish have at least some tetrodotoxin in them, certain organs (ovaries, liver, intestine) have the highest concentrations. There is no antidote for tetrodotoxin poisoning. It’s a horrible death, in which cognitive function appears to continue while paralysis slowly sets in, and, ultimately, breathing fails.
Amazingly, pufferfish is a delicacy in Japan where over 10,000 tons are consumed a year at enormous expense: One can easily spend $200 per person at a fancy fugu restaurant. So what’s the appeal of pufferfish-eating? At least some of the draw is the delicate taste of the flesh which has been described as “not unlike the smell of Spring rain falling on a rock.” More importantly, traces of tetrodotoxin (present in the those parts of the pufferfish which are safe to consume) give a tingling sensation in the mouth, and some say, a subtle euphoria. Finally, there may be a thrill factor at work here. In 1958 when fugu restaurants were still poorly regulated, 176 people died in them, chopsticks in hand. As late as 1975, a celebrated Kabuki actor, the eighth in a famous line called Mitsugoro Bando, who had been designated a “National Living Treasure” by the Japanese government, died in a Kyoto fugu restaurant.
These days, fugu restaurants are much safer (the annual restaurant death toll hovers in the single digits—although more die from home preparation). They have special government-licensed chefs who train for years before being allowed to work unsupervised. By law, and the moral code of their profession, these chefs are required to taste every dish they prepare. Fugu may only be prepared in kitchens used solely for this purpose. Impressively, even the waste from fugu preparation must be disposed of in hermetically sealed containers handled by specially trained companies: This, after some homeless people were killed by toxic fugu dumpster-diving.
So, if you’re a thrill-seeking extreme gourmet, fugu might just be the ticket. Me, I’m fond of my voltage-sensitive sodium channels and so I’m taking a clue from Japanese law. Fugu is the one food that the Emperor and his family are absolutely prohibited from eating.