How Does Snake Venom Work?

Snake venom is the poisonous, typically yellow fluid stored in the modified salivary glands of venomous snakes. There are hundreds of venomous snake species that rely on the venom they produce to debilitate and immobilize their prey. Venom is composed of a combination of proteins, enzymes, and other molecular substances. These toxics substances work to destroy cells, disrupt nerve impulses, or both. Snakes use their venom cautiously, injecting amounts sufficient to disable prey or to defend against predators. Snake venom works by breaking down cells and tissues, which can lead to paralysis, internal bleeding, and death for the snake bite victim. For venom to take effect, it must be injected into tissues or enter the bloodstream. While snake venom is poisonous and deadly, researchers also use snake venom components to develop drugs to treat human diseases.

What's in Snake Venom?Snake Venom

Snake venom is the fluid secretions from the modified salivary glands of venomous snakes. Snakes rely on venom to disable prey and aid in the digestive process.

The primary component of snake venom is protein. These toxic proteins are the cause of most of the harmful effects of snake venom. It also contains enzymes, which help to speed up chemical reactions that break chemical bonds between large molecules. These enzymes aid in the breakdown of carbohydrates, proteins, phospholipids, and nucleotides in prey. Toxic enzymes also function to lower blood pressure, destroy red blood cells, and inhibit muscle control.

An additional component of snake venom is polypeptide toxin. Polypeptides are chains of amino acids, consisting of 50 or fewer amino acids. Polypeptide toxins disrupt cell functions leading to cell death. Some toxic components of snake venom are found in all poisonous snake species, while other components are found only in specific species.

Three Main Types of Snake Venom: Cytotoxins, Neurotoxins, and Hemotoxins

Although snake venoms are composed of a complex collection of toxins, enzymes, and non-toxic substances, they have historically been classified into three main types: cytotoxins, neurotoxins, and hemotoxins. Other types of snake toxins affect specific types of cells and include cardiotoxin, myotoxins, and nephrotoxins.

Cytotoxins are poisonous substances that destroy body cells. Cytotoxins lead to the death of most or all of the cells in a tissue or organ, a condition known as necrosis. Some tissue may experience liquefactive necrosis in which the tissue is partially or completely liquefied. Cytotoxins help to partially digest the prey before it is even eaten. Cytotoxins are usually specific to the type of cell they impact. Cardiotoxins are cytotoxins that damage heart cells. Myotoxins target and dissolve muscle cells. Nephrotoxins destroy kidney cells. Many venomous snake species have a combination of cytotoxins and some may also produce neurotoxins or hemotoxins. Cytotoxins destroy cells by damaging the cell membrane and inducing cell lysis. They may also cause cells to undergo programmed cell death or apoptosis. Most of the observable tissue damage caused by cytotoxins occurs at the site of the bite.

Neurotoxins are chemical substances that are poisonous to the nervous system. Neurotoxins work by disrupting chemical signals (neurotransmitters) sent between neurons. They may reduce neurotransmitter production or block neurotranmitter reception sites. Other snake neurotoxins work by blocking voltage-gated calcium channels and voltage-gated potassium channels. These channels are important for the transduction of signals along neurons. Neurotoxins cause muscle paralysis which may also result in respiratory difficulty and death. Snakes of the family Elapidae typically produce neurotoxic venom. These snakes have small, erect fangs and include cobras, mambas, sea snakes, death adders, and coral snakes.

Examples of snake neurotoxins include:

Calciseptine: This neurotoxin disrupts nerve impulse transduction by blocking voltage-gated calcium channels. Black Mambas use this type of venom.

Cobrotoxin, produced by cobras, blocks nicotinic acetylcholine receptors resulting in paralysis.

Calcicludine: Like calciseptin, this neurotoxin blocks voltage-gated calcium channels disrupting nerve signals. It is found in the Eastern Green Mamba.

Fasciculin-I, also found in the Eastern Green Mamba, inhibits acetylcholinesterase function resulting in uncontrollable muscle movement, convulsions, and breathing paralysis.

Calliotoxin, produced by Blue Coral Snakes, targets sodium channels and prevents them from closing, resulting in paralysis of the entire body.

Hemotoxins are blood poisons that have cytotoxic effects and also disrupt normal blood coagulation processes. These substances work by causing red blood cells to burst open, by interfering with blood clotting factors, and by causing tissue death and organ damage. Destruction of red blood cells and the inability of blood to clot causes serious internal bleeding. The accumulation of dead red blood cells can also disrupt proper kidney function. While some hemotoxins inhibit blood clotting, others cause platelets and other blood cells to clump together. The resulting clots block blood circulation through blood vessels and can lead to heart failure. Snakes of the family Viperidae, including vipers and pit vipers, produce hemotoxins.

Snake Venom Delivery and Injection System

Most venomous snakes inject venom into their prey with their fangs. Fangs are highly effective at delivering venom as they pierce tissue and allow venom to flow into the wound. Some snakes are also able to spit or eject venom as a defense mechanism. Venom injection systems contain four main components: venom glands, muscles, ducts, and fangs.

Venom Glands: These specialized glands are found in the head and serve as production and storage sites for venom.

Muscles: Muscles in the head of the snake near venom glands help to squeeze venom from the glands.

Ducts: Ducts provide a pathway for the transport of venom from the glands to the fangs.

Fangs: These structures are modified teeth with canals that allow for venom injection.

Snakes of the family Viperidae have an injection system that is very developed. Venom is continuously produced and stored in venom glands. Before vipers bite their prey, they erect their front fangs. After the bite, muscles around the glands force some of the venom through the ducts and into the closed fang canals. The amount of venom injected is regulated by the snake and depends on the size of the prey. Typically, vipers release their prey after the venom has been injected. The snake waits for the venom to take effect and immobilize the prey before it consumes the animal.

Snakes of the family Elapidae (ex. cobras, mambas, and adders) have a similar venom delivery and injection system as vipers. Unlike vipers, elapids do not have movable front fangs. The death adder is the exception to this among elapids. Most elapids have short, small fangs that are fixed and remain erect. After biting their prey, elapids typically maintain their grip and chew to ensure optimal penetration of the venom.

Venomous snakes of the family Colubridae have a single open canal on each fang which serves as a passageway for venom. Venomous colubrids typically have fixed rear fangs and chew their prey while injecting venom. Colubrid venom tends to have less harmful impacts on humans than the venom of elapids or vipers. However, venom from the boomslang and twig snake has resulted in human deaths.

Can Snake Venom Harm Snakes?

Snake Eating Frog

This specklebelly keelback is eating a frog. Thai National Parks/Flickr/CC BY-SA 2.0

Since some snakes use venom to kill their prey, why isn't the snake harmed when it eats the poisoned animal? Venomous snakes are not harmed by the poison used to kill their prey because the primary component of snake venom is protein. Protein-based toxins must be injected or absorbed into body tissues or the bloodstream to be effective. Ingesting or swallowing snake venom is not harmful because the protein-based toxins are broken down by stomach acids and digestive enzymes into their basic components. This neutralizes the protein toxins and disassembles them into amino acids. However, if the toxins were to enter blood circulation, the results could be deadly.

Venomous snakes have many safeguards to help them to remain immune to or less susceptible to their own venom. Snake venom glands are positioned and structured in a way that prevents the venom from flowing back into the snake's body. Poisonous snakes also have antibodies or anti-venoms to their own toxins to protect against exposure, for instance, if they were bitten by another snake of the same species.

Researchers have also discovered that cobras have modified acetylcholine receptors on their muscles, which prevent their own neurotoxins from binding to these receptors. Without these modified receptors, the snake neurotoxin would be able to bind to the receptors resulting paralysis and death. The modified acetylcholine receptors are the key to why cobras are immune to cobra venom. While poisonous snakes may not be vulnerable to their own venom, they are vulnerable to the venom of other poisonous snakes.

Snake Venom and Medicine

In addition to the development of anti-venom, the study of snake venoms and their biological actions has become increasingly important for the discovery of new ways to fight human diseases. Some of these diseases include stroke, Alzheimer's disease, cancer, and heart disorders. Since snake toxins target specific cells, researchers are investigating the methods by which these toxins work to develop drugs that are able to target specific cells. Analyzing snake venom components has aided in the development of more powerful pain killers as well as more effective blood thinners.

Researchers have used the anti-clotting properties of hemotoxins to develop drugs for the treatment of high blood pressure, blood disorders, and heart attack. Neurotoxins have been used in the development of drugs for the treatment of brain diseases and stroke.

The first venom-based drug to be developed and approved by the FDA was captopril, derived from the Brazilian viper and used for the treatment of high blood pressure. Other drugs derived from venom include eptifibatide (rattlesnake) and tirofiban (African saw-scaled viper) for the treatment of heart attack and chest pain.

Sources

Adigun, Rotimi. “Necrosis, Cell (Liquefactive, Coagulative, Caseous, Fat, Fibrinoid, and Gangrenous).” StatPearls [Internet]., U.S. National Library of Medicine, 22 May 2017, www.ncbi.nlm.nih.gov/books/NBK430935/.

Takacs, Zoltan. “Scientist Discovers Why Cobra Venom Can't Kill Other Cobras.” National Geographic, National Geographic Society, 20 Feb. 2004, news.nationalgeographic.com/news/2004/02/0220_040220_TVcobra.html.

Utkin, Yuri N. "Animal Venom Studies: Current Benefits and Future Developments." World Journal of Biological Chemistry 6.2 (2015): 28–33. doi:10.4331/wjbc.v6.i2.28.

Vitt, Laurie J., and Janalee P. Caldwell. “Foraging Ecology and Diets.” Herpetology, 2009, pp. 271–296., doi:10.1016/b978-0-12-374346-6.00010-9.

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How Does Snake Venom Work?