Dying to Know: how do neurotoxins work?

August 6, 2019

Written by: Rebecca Somach

 

When we’re told an animal is ‘venomous’ or ‘poisonous’, our natural instinct is to get as far away from it as we can. Snakes, frogs, and lizards are often brightly colored as a natural warning sign. We wear gloves and are careful around chemicals that are labeled with a skull and crossbones that are the universal symbol of deadly poisons. We know that certain poisons are extremely harmful to us, but have you stopped to wonder why these substances are so harmful?

poison-1481596_640

“Toxins” are defined as substances that are produced by living organisms that are toxic to other living organisms1. In animals, a ‘poison’ is a toxin that is produced by the animal. That’s slightly different than venom, which an animal will inject into another organism to cause damage or defend themselves. Poisons and venoms are common in the animal kingdom, but just as animals are very different from one another, these toxins are also different from one another. We can categorize toxins in different ways, including how long they take to work in the victim, or the way that the toxin actually works. Some toxins kill any cell they come across while others aim for specific targets or cell types. For example, myotoxins specifically target and damage muscle tissue and neurotoxins damage neural tissue. However, not all toxins work the same way. Neurotoxins that developed in different animals or plants all act in different ways to damage neurons.

To understand how different poisons might hurt neurons, keep in mind that neurons rely on the concentrations of specific molecules, or ions, inside and outside the neuron. Special proteins known as ion channels help to regulate what gets in and out of any neuron (Figure 1). Normally, these ion channels help the neurons send signals to other neurons because the flow of ions triggers the release of neurotransmitters. Many neurotoxins will target these channels and stop ions from moving in or out of the cells, which prevents or alters neural communication.

ion channels
Figure 1: The cell membrane (blue) normally keeps ions (red) from flowing into or out of a cell. However, proteins called channels (green) can allow these ions to flow. Normally, the flow of ions through these channels is what causes neural communication.

For example, let’s look at the toxins produced by cone snails. These creatures are a type of snail that lives in the ocean. To capture their prey, they will fire a small harpoon at their targets. That harpoon-like structure is covered with venom called conotoxin. Different types of conotoxin target various channels that let potassium, sodium and calcium ions into and out of neurons. When the snail injects its venom, the concentrations of these molecules inside and outside of neuronal cell bodies are altered and neurons are not able to send signals and communicate2. The end result of this assault on the neuromuscular system is immobilization of the cone snail’s prey.

Neurotoxins don’t just target ion channels though. The bacteria Clostridium botulinum produces botulinum toxin, which interferes with how neurons and muscles communicate differently than conotoxin. When the neurotransmitter acetylcholine is about to be released, it is packaged inside of a compartment in a neuron called a vesicle. Normally, this vesicle then merges with the cell wall to let acetylcholine out so it can bind to the muscle. To do this, the vesicle has the help of proteins called the SNARE proteins. The botulinum toxin cuts those SNARE proteins, making them useless3. The acetylcholine is then trapped inside of the neurons and muscles can’t move, leading to paralysis. While this sounds very severe, the cosmetics world has taken advantage of this to prevent muscle movement in the face, using this toxin by its common brand name of Botox. Since the facial muscles have limited movement after a Botox injection, they also don’t form wrinkles.

Neuroscientists have long been fascinated by how these poisonous substances work, but they have taken these interests one step further. In many research labs, these toxins are actually used as tools. Often, the goal of designing any chemical is to have it act on a specific target while not affecting other targets. Nature has already designed toxins that target specific protein channels, so scientists can use this to their advantage. If a neuroscientist wants to explore if calcium is important to a neuron or to a type of behavior, they can use a specific type of conotoxin, called omega conotoxin, to block calcium channels. Many of the neurotoxins that target specific ion channels are used in research. This includes tetrodotoxin, a powerful toxin which is found in many marine fish and blocks sodium channels, and chlorotoxin, which blocks chloride channels and comes from the venom of the deathstalker scorpion. Without these types of toxic substances, neuroscientists would not be able to figure out what channels are important for neural signaling or how these signals are changed in disease.

From the animals and plants they are made in, to the ways they work in the body, to the ways humans have made use of them, toxins are a fascinating part of the neuroscience world. Rather than avoiding them at all costs, people have been able to work with these poisons to understand them and use them to benefit others. If you see a poisonous or venomous animal, take a moment to appreciate how that poison actually works—but you might want to stand back first.

 

 

 

References:

  1. Merriam-Webster Dictionary
  2. Terlau, H. Olivera, B. (2004) Conus Venoms: A Rich Source of Novel Ion Channel-Targeted Peptides, Physiological Reviews
  3. Lu B. (2015). The destructive effect of botulinum neurotoxins on the SNARE protein: SNAP-25 and synaptic membrane fusion. PeerJ, 3, e1065. doi:10.7717/peerj.1065

 

 

Image Credits:

Pixabay

https://pixabay.com/photos/snake-rattlesnake-reptile-nature-3515122/

https://pixabay.com/illustrations/poison-bottle-medicine-old-symbol-1481596/

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