Snake Venoms and the Neuromuscular Junction

Robert L. Lewis, M.D.; Ludwig Gutmann, M.D.


Semin Neurol. 2004;24(2) 

In This Article

Abstract and Introduction

There are ~ 420 venomous species of snakes living on the earth. Their venoms, each unique, can affect multiple organ systems. The venoms have a predilection for the peripheral nervous system where the neuromuscular junction is a favorite target. Those venoms affecting the release of acetylcholine from the presynaptic membrane are called β-neurotoxins and those affecting the postsynaptic membrane are called α-neurotoxins. α-Bungarotoxin has been used in quantitative studies of acetylcholine receptor density and turnover and for the assay of antibodies directed against the acetylcholine receptor. A unique feature of timber rattlesnake venom is its ability to cause clinical myokymia. This likely results from a blockade of voltage gated K+ antibodies.

There are ~ 2340 species of snakes living on the earth and more than 420 species are venomous.[1] Venomous snakes are found on all continents except Antarctica.[2] It has been reported that around 5 million snakebites occur worldwide each year, causing ~ 125,000 deaths. Snakebites are more common in tropical regions and in agricultural areas where there is a high likelihood of contact with snakes.[2] Rattlesnakes cause most snakebite-related fatalities in the United States, and 5 to 10 deaths occur per year from snakebites in the United States.[3] People provoke bites by handling or even attacking snakes in certain parts of the United States.[4] There are ~ 45,000 snakebites per year in the United States, and an estimated 8000 are by venomous snakes.[5]

Venomous snakes are represented in only five families. These are the Colubridae (colubrids), Elapidae (elapids), Hydrophiidae (sea-snakes), Viperidae (true vipers), and Crotalidae (pit vipers).[6] The family Colubridae are the largest of all families of snakes encompassing 80 to 85% of all living snakes. Many snakes in this family are well known and harmless; however, some are venomous. The venom fangs are grooved and mounted at the rear of the upper jaws in contrast to the front as in all other venomous snakes. They are found on all continents except Antarctica.[6] The family Elapidae includes kraits, cobras, mambas, and coral snakes. Members of this family typically have a small head with short, fixed fangs mounted at the front of the jaw that fit into grooved slots in the buccal floor when the mouth is closed. Some members of this family are venomous; however, not all are dangerous to man. Only the coral snakes are indigenous to the United States.[6]

The family Hydrophiidae comprises the sea snakes and has evolved several adaptations to allow almost complete existence in the water. They have specialized flattened tails used for swimming. Due to their need to breathe air, they have valves over their nostrils, which are closed underwater where they swim near the bottom in shallow water to feed. Only a small proportion of bites are fatal to man because the snake can control the amount of venom injected. They are usually found in the warm waters of the Indian and Pacific Oceans.[6,7] The family Viperidae is the most diverse family of venomous snakes. Most vipers have numerous and heavily keeled scales and possess a large, flattened triangular head. The venom fangs are large, which permit deep penetration during envenomation of prey. They have a hinged-fang mechanism, which allows for their storage against the roof of the mouth when not in use; opening of the jaw is not always associated with the erection of the fangs. They are found throughout Europe, Africa, Asia, and the Americas.[6] The family Crotalidae can be considered a subfamily of Viperidae. They possess heat sensitive pits located between the nostrils and the eyes. These pits allow the animals to detect small variations in temperature above ambient temperature from a short distance. This facility evolved to assist in hunting warm-blooded prey, especially at night. The Crotalidae are considered New World snakes and are found in the Americas and parts of southeast Asia.[6]

Snake venoms have been the subject of scientific investigation for quite some time; the first toxin to be isolated was crotoxin from the Brazilian rattlesnake.[7] Snake venoms are colorless to dark amber liquids that contain complex mixtures of small peptides with diverse pharmacological properties.[8] Venom is a modified form of saliva and probably evolved to aid in capture of prey,[9] assist in chemical digestion,[8] and defense against predators.[9] Snakes use glands to inject venom, which are actually modified salivary glands that are situated below the eyes.[10] During envenomation, the venom passes from the venom gland through a duct into the snake's fangs and ultimately into prey.[11] The amount of venom injected per bite depends on species of the snake, the elapsed time since the last bite, and the degree of threat the snake feels as well as the size of the prey.[9]

The numerous toxins present in snake venoms result in injury to several organ systems including muscles, kidneys, and blood coagulation disturbances. The morbidity related to venomous snake bites is dependent upon the species of snake, the quantity of venom administered, and access to appropriate medical treatment.[9] Arguably, the most important constituents in snake venom are neurotoxins. Neurotoxins have a high preponderance for the peripheral nervous system because most do not cross the blood brain barrier.[9] They are responsible for the neuromuscular weakness and paralysis that ensues after sustaining a bite from a venomous snake.[12] Following envenomation, the cranial nerves are usually affected first, which results in ptosis, ophthalmoplegia, dysarthria, dysphagia, and drooling. This progresses to weakness of limb muscles, paralysis of the respiratory muscles, and ultimately death if prompt treatment is not initiated.[2]