The key to understanding the neurotoxicity of snake & spider bites (Part 2)

In this blog we will discuss how different neurotoxins (snake & spider) can interfere with nerve impulse conduction & muscle contractions. We will do this using the wash basin model  to see how toxins change the effective ACh concentrations at the neuromuscular junction by altering the a) input or b) output of Ach or c) by blocking ACh attachment to its receptor in the muscle cell membranes.

We will mainly discuss three different snake species to illustrate these points (Figure 1). At the end we will show how the black widow spider bite also influences ACh metabolism.

Figure 1: How different snake venoms interfere with ACh metabolism. (click to enlarge)

a)   Increasing ACh input:- The black (Dendroaspis polylepis) & green (Dendroaspis angusticeps) are highly venomous fast moving snakes. They are members of the cobra family (Elapids) but display a much smaller hood when threatened than for example the Cape cobra. Dendroaspis literally meaning “tree snake”, however although the green mamba is arboreal the black mamba is mainly terrestrial. Their highly toxic venom is appropriately called “dendroxin”. This blocks potassium channels along the nerve increasing the electrical potential of its membranes thus increasing electrical impulses to the muscle. This increases release of ACh at the neuromuscular conductions causing muscle hyperexcitability & convulsions i.e. muscle are excessively stimulated by the excess input of ACh into the synaptic space. So this action is called pre-synaptic.

b)  Decrease ACH output:-The mambas also have a second toxin called “fasciculins”. These work by blocking the action of AChE in the muscle receptor & thus ACh accumulates again producing excess muscle excitability which exhausts the respiratory diaphragm resulting in respiratory failure. The medical term for muscle twitches is “fasciculation” which explains the origin of this toxin’s name. So this action is referred to as being post-synaptic.

c)   Block the ACH receptor:- Cobra toxin is a well known example. This toxin also works post-synaptically. The cobras are a highly venous species belonging to the Elapid family. They have the characteristic wide-spreading of the hood when threatened. Some of the family members e.g. ringhals can spit their venom which can irritate the eye because it also has cytotoxic components i.e. enzymes. The neurotoxic venom of the cobra works by blocking the ACh binding site on the muscle ACh receptor (see lock & key analogy in part 1 of the blog). This results in paralysis & respiratory failure if not rapidly treated e.g. gentle occlusion of lymphatic’s of the limb with a bandage, immobilization, specific antivenom (lock & key analogy), & respiratory support.

Well that’s a brief guide to the ins & outs of the neurotoxic venoms in snakes. Briefly on the basis of the input ouput model lets also now briefly discuss the venom of the  black widow spider (Latrodectus). Its venom affects ACh input by triggering excessive ACh release from their vesicles in the nerve endings. This excitation of the muscles causes  tetany.

It’s interesting to note a few other poisons & diseases that cause muscle failure by related mechanisms. There is an auto-immune muscle disease called “myasthenia gravis”; the patient produces antibodies which block the ACh receptor. Curare is a plant poison used to hunt animals in the Amazon jungle. Its derivatives are now used in anesthetics to paralyze patients undergoing surgery. Sarin, a potent nerve poison used in gas warfare, inactivates AChE resulting in ACh accumulation with depolarization & activation of all muscles.

In the last part 3 of these posts on snake venom we will discuss how the mongoose has been able to overcome the neurotoxic effects of cobra venom.

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