The Act of Envenomation
Like all vipers, rattlesnakes have a pair of long, movable hypodermic, needle-like fangs that fold against the roof of the mouth when not in use. These fangs are connected to venom glands on each side of the rattlesnake’s head. Rattlesnake heads are large to accommodate these venom glands. During a strike, venom is pumped by muscles surrounding the venom glands, through the fangs into prey. Rattlesnakes are also known as pit-vipers and possess two heat-sensitive pits on either side of their face. These pits are sense organs and detect radiant heat, and aid rattlesnakes in locating prey and increase striking accuracy. These pits are extremely sensitive and can distinguish differences in temperature of less than 0.2 C. These advanced systems evolved in pit-vipers as a means of obtaining food. It is the most advanced system that snakes have for capturing prey, and reduces the chances of injury to the snake.
The venom of rattlesnakes is actually a digestive enzyme and is a complex mixture of proteins. The primary purpose of venom is to kill and digest prey. Venom is used in defense only as a last resort. Some venoms attack the nervous system (neurotoxic) while others attack the blood and tissue (hemotoxic). The eastern diamondback, like most rattlesnakes, has a combination of both types, but unlike most vipers, it has more neurotoxic properties.
Carl Barden extracts a dose of venom from a Eastern Diamondback rattlesnake at his facility in DeLand Florida. Note the copious amount in the bottom of the glass from one bite.
How Does Venom Work?
Why do they have venoms, and how does that venom work? There are venomous and poisonous species basically in all kinds of ecosystems, and they are distributed everywhere in the animal kingdom.
The three most important and basic reasons that animals have venom are prey-immobilization, predigestion and defense. Of course, poisonous animals, which have toxin distributed throughout their bodies, don’t have all these functions. With venomous snakes, venomous lizards and scorpions, for example, all three functions are achieved by the venoms of each animal.
The venoms of snakes are produced, or secreted, in the main venom gland, which works like a modified salivary gland, located in both sides of the head. That’s where the venom is stored. When the snake bites, the venom travels through the primary duct across the accessory venom gland, then via the secondary duct to the base of the functional fang, which has a long tunnel starting at the base of the fang and ending at the tip of the fang. That functional fang is responsible for injecting the venom into the body of the victim or the prey animal.
What happens if a snake bites into a rat and the rat jumps and the functional fang accidentally breaks off into the body of the rat? Then the most advanced replacement fang will take its place, so the snake will not be left without a working fang and will remain capable of delivering more bites even after the functional fang is broken off.
If you look at an actual skull of a venomous snake, like a rattlesnake, you can clearly see the functional fang sitting on the upper jaw. The growing replacement fangs are folded just behind the functional fang, and on the bottom and top of the mouth are the teeth, which have nothing to do with venom injection. These teeth just serve to grab the prey and help to swallow it.
Venomous animals, like the snakes, have a special apparatus that produces the venom and injects it in the body of the animal.
Why don’t venomous animals poison themselves?
If snakes and all of these venomous animals have very potent toxin, what happens if the animal bites itself? Snakes and other venomous animals also have to have the neuromuscular junction. From an evolutionary perspective, there is pressure on the snake to have a toxin that works against a wide variety of animals. This is because if you have a toxin that is potent against so many taxa, then you have many more choices of food sources and you have a much more potent weapon to defend yourself.
Chemistry of Venoms:
What do animal venoms contain? Animal venoms are mixtures of 20 to 25 different kinds of molecules dissolved in water. Most frequently, venomous species have proteins or smaller polypeptides ranging from 30 to 80 amino acid residues. The poisonous species primarily have alkaloids, which are small molecules that have very strong biological effects.
Acetylcholine receptors, potassium channels, calcium channels–these are different receptors on the surface of the nerve or muscle cells that have a very basic role in maintaining and propagating action potential and muscle contraction. And because one of the primary functions of animal venoms is to immobilize the prey or the predator, toxins are targeted against those molecules that play a very basic role in the locomotion of the prey animal.
Many animal toxins are targeted against the acetylcholine receptor because of its function, and it is found everywhere in the animal kingdom. There are some toxins, for example, dendrotoxins and some bungarotoxins, that also attack the neuromuscular junction, but they’re not acting on the muscle cell. They’re acting by inhibiting acetylcholine release from the nerve terminal or they’re causing abnormally high release from the nerve terminal. The release of so much acetylcholine, which also leads to a neuromuscular blockage, will clinically lead to a failure of respiration and therefore lead to the death of the victim.
Venomous and poisonous species in very different taxa have toxins with very similar actions that compose these poisons and venoms. For example, toxins that act on the very same acetylcholine receptor of animals have been isolated from corals, cone shells, sea snakes and cobras. Similarly, toxins interfering with the normal operation of nerve cells by acting on potassium channels have been isolated from scorpions, bees and mambas. The important message here is that all animal venoms, regardless of which group produces it, are targeted against key elements of locomotion because they have to immobilize the predator or prey animal in order to be an evolutionary success.
The sodium channel is a big protein in the membrane of the nerve and muscle cells, and it makes an excellent target for different toxins, such as scorpion toxins, anemone toxins and amphibian toxins. While different kinds of poison arrow frogs, newts from California and birds from Papua New Guinea–there are three species of poisonous birds–have tetrodotoxin and homobatrachotoxin in their bodies, all of these toxins bind to specific regions of the same sodium channel. Batrachotoxin, which is not a polypeptide and can therefore go through the lipid bilayer, binds more in the core part of that sodium channel. Then there is beta-scorpion toxin, which is a big polypeptide that binds to the surface of the sodium channel.
What does this mean pharmacologically? A current can be detected when potassium ions go through a potassium channel, and since many of these channels are targets for animal venoms, they can be blocked. With dendrotoxin, for example, which is a toxin isolated from the elapid mamba snake, a relative of the cobra, you can see a reduction of the current experimentally as you start to increase the toxin concentration. This is what happens when an animal gets bitten by a venomous snake. The ion channels get blocked, and that may lead to respiratory paralysis.
Venoms as enzymes
Toxins attack the nerve and muscle cells, but enzymes are another important component in animal venoms. Enzymes don’t exist in the venom of all animals, only in venomous species. The poisonous species normally don’t have enzymes, because enzymes have a digestive function. The venom gland of snakes, for example, is a modified salivary gland, so it still retains its digestive function, and that’s why you find so many enzymes in snake venoms.
Enzymes are found in all snake venoms, and many of these enzymes are also found in other animal venoms. Some enzymes are found only in the venoms of vipers and pit vipers, while others are found only in the venom of elapids, such as cobras and sea snakes. Some specific enzymes are unique for particular groups of species. If you follow the enzyme nomenclature, you realize they break down tissues; they are mostly proteinases, nucleases, phospholipases–they “chew up,” or digest, the proteins of the prey animal.
Crotalase, a snake venom enzyme that is isolated from a North American rattlesnake, acts on fibrinogen. Fibrinogen is a molecule in the blood that is needed for coagulation. In normal physiological conditions, thrombin slices off fibrinopeptides A and B and the remaining monomer is able to polymerize, and through other steps will cause the blood to clot. So what does snake venom do? Once crotalase, in the snake venom, gets into the circulation of an animal, it splits off only fibrin peptide A and results in a monomer that is unable to polymerize. So the animal who has been bitten by that snake will have internal bleeding, because all of the fibrinogens will be consumed by the crotalase and will be unable to form the polymer that lets the blood clot.
