Journal of Pharmacy and Pharmacology 4 (2016) 715-720 doi: 10.17265/2328-2150/2016.12.009

Elapidae Snake Bites—Biophysical Aspects of the

Neuroparalytic Envenomation

Yuliyan Naydenov1, Teodora Karachorova1 and Detelina Ilieva2

1. Department of Medicine, Medical University of Varna, Varna 9002, Bulgaria

2. Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Varna, Varna 9002, Bulgaria

Abstract: Snakebite is classified by the WHO (World Health Organization) as a neglected tropical disease, envenoming in a significant public health problem in tropical and subtropical regions. Neurotoxicity is a key feature of different types of envenomations and there are many unanswered questions regarding this manifestation. Acute neuromuscular weakness with respiratory involvement is the most clinically important neurotoxic effect. We present how the neuroparalytic poison affects the human body and what actually happens when the poison is injected into the human body. Neuroparalytic poisons are one of the most lethal, because they cause paralysis of the eye, throat and chest muscles. A well-known member of the Elapidae family is the cobra. Bungarotoxins are a group of closely related

neurotoxin proteins. The -bungarotoxin inhibits the binding of acetylcholine (ACh) to nicotinic acetylcholine receptors;

-bungarotoxin and -bungarotoxins act presynaptically causing excessive acetylcholine release and subsequent depletion.

Key words: Elapidae, action potential, neuromuscular synapse, poison, bungarotoxin, paralysis.

1. Introduction

Neuroparalytic envenomation, caused by Elapid

snake bites, is one of the most lethal, leading to

paralysis of the eye, throat and chest muscles [1]. A

member of Elapidae family is the well-known cobra

(the biggest specie which reaches up to 5.6 m (170 ft).

The snakes live in the tropical and subtropical regions

of Asia, Australia, Africa, North and South

America—that is the reason why most of the clinical

cases are from India, Taiwan, China (Fig. 1).

Professor Chuan-Chiung Chang [2] from The National

Taiwan University was the one who isolated in 1950

the neurotoxic protein in the snake venom

bungarotoxin. Thirteen years later, the different types

were distinguished: α-bungarotoxin, β-bungarotoxin

and γ-bungarotoxin.

The bungarotoxin consists of proteins and lipids and

its neuroparalytic effect is caused by the curare-like

action of the toxin at the presynaptic and postsynaptic

levels of the neuron, followed by neuromuscular

Corresponding author: Yuliyan Naydenov, Ph.D. student,

research fields: Elapidae snake bite and venom.

blockade—a failure of impulse transmission. The

mechanism of action of any of the three types

bungarotoxins is different and to be understand easily;

let us briefly review the current knowledge on how the

neuromuscular impulse travels through the

neuromuscular junction.

The process consists of the following steps:

Step 1: Action potential travels through the axon

to the terminal part of the axon (Fig. 2);

Step 2: The generated voltage opens Са2+

channels and Са2+ ions enter the terminal part of the

axon;

Step 3: Diffusion of Са2+ ions causes exocytosis

and release of acetylcholine from the vesicles;

Step 4: Acetylcholine enters the presynaptic cleft

and connects with the acetylcholine receptors, which

consist of five protein subunits. Then, the conformation

of the subunits changes and Nа+ channels open (Fig. 3);

Step 5: Nа+ ions enter the muscle fiber, while K+

ions enter the synaptic cleft—this leads to

depolarization of the membrane. When a certain level

of depolarization is reached, action potential travels

along the sarcolemma and muscle contraction occurs;

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Fig. 5 Sites of action of snake neurotoxins and other substances on the neuromuscular junction. Schematic representation of the neuromuscular junction showing different sites of action of snake neurotoxins, other toxins, and pharmacological substances, and sites of involvement in disease states (examples indicated where relevant) [4].

such as “cobra envenomation”, “cobra venom”,

“bungarotoxin” and “neuromuscular junction”.

Altogether we have put the most relevant information

into our paper.

3. Bungarotoxins and

The -BGT (-bungarotoxin ) is more lethal. He

affects the terminal part of the axon and blocks the

release of acetylcholine, but does not affect the

sensitivity of the acetylcholine receptors to the

acetylcholine. The mechanism of the -BGT is

complex. His effect is similar to phospholipase A2,

which hydrolyses phosphatidylcholine, but it also

connects and blocks К+ channels. The level of

neuromuscular blockade depends on the

temperature—it lowers with the decrease of

temperature. The victims of -BGT do not respond to

antidotes. Drugs, such as Anticholinesterases, have a

very little or no effect. Harris and colleagues

demonstrate, that an hour after the bite, a lot of

presynaptic terminal structures show signs of physical

destruction (destruction of the mitochondria, Schwann

cells enter the synaptic cleft) and are deprived of

synaptic vesicles and, after 24 h, 70% of the muscle

fibers are de-innervated. That is why envenomations

caused by -neurotoxins, are often followed by heavy

prolonged paralysis, which are very difficult to be

treated. The recovery period is long while the muscle

terminal of the axon regenerates and new

neuromuscular junction is formed. Re-innervation

occurs after three days and ends after seven days. That

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Elapidae Snake Bites—Biophysical Aspects of the Neuroparalytic Envenomation

720

myasthenia gravis and to evaluate the quantity of the

antibodies that have targeted these receptors and the

activity of the disease.

Acknowledgments

Micro project “Elapidae Snake Bites—Biophysical

Aspects of the Neuroparalytic Envenomation” was

presented to the Department of Medical Physics and

Biophysics, Faculty of Pharmacy, Medical University

of Varna and the Second Pharmaceutical Business

Forum with Scientific and Practical Conference, 2015.

References

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Dysautonomia and Central Nervous System Signs.” Q.J.M. 106 (9): 865-6.

[2] Hodgson, W. C., and Wickramaratna, J. C. 2002. “In Vitro Neuromuscular Activity of Snake Venoms.” Clinical and Experimental Pharmacology and Physiology 29 (9): 807-14.

[3] Rasmussen, A. R., Murphy, J. C., Ompi, M., Gibbons, J. W., and Uetz, P. 2011. “Marine Reptiles.” PLoS ONE 6 (11): e27373.

[4] Ranawaka, U. K., De Silva, H. J., and Lallo, D. G. 2013. “Neurotoxicity in Snakebite—The Limit of Our Knowledge.” PLOS Neglected Tropical Diseases 7 (10): e2302.

[5] Harsoor, S. S., Gurudatta, C. L., Balabhaskar, S., Kiranchand, N., Raghavendra, B. 2006. “Ventilatory Management of Patients with Neuroparalytic Envenomation.” Indian J. Anaesth. 50 (6): 452 -5.