The key to understanding the neurotoxicity of snake & spider bites (Part 1)

I want to briefly discuss the biochemistry underlying the toxic effects of venoms trying to explain basic concepts with my beloved wash-basin analogy & also the lock & key theory.

Snake & spider venom contain various toxic substances. These via various enzymes can cause local tissue destruction at the site of the bite or after absorption damage other distant organs e.g. paralyze respiratory muscles or cause diffuse thrombosis &/or hemorrhage. (Figure 1)

Fig 1. Mechanisms of snake venom toxicity in South Africa (click to enlarge)

I will concentrate on the action of neuromuscular toxins & so we need to start by briefly describing how normally the message from a nerve is passed on to a muscle e.g. the respiratory diaphragm, to produce a contraction. The signal in a nerve is conducted via changes in electrolyte concentrations along the nerve membranes which produce an electrical current. But at the junction of the nerve & the muscle the signal is converted to a chemical signal that passes over the neuromuscular junction to stimulate the muscle contraction. The essential chemical messenger is acetylcholine (Ach) which is continually being made in the nerve endings & stored in vesicles, & then released into the synaptic space (between the nerve ending & the muscle) to bind with a protein receptor built into the phospholipid membrane of the muscle cell wall (Figure 2).

Figure 2: neuromuscular junction showing ACh release, binding, & catabolism by AChE (Click to enlarge)

The ACh fits into the binding site on the protein ACH receptor exactly analogous to the way a key fits a lock (see previous blog on how temperature affects enzymes activity). This triggers the opening up of a channel into the muscle cell & electrolytes in the synapse flow into the muscle cell & activate a muscle contraction (Figure 3).

Figure 3: ACh receptor in the phospholipid membrane of the muscle cell opening its channel when ACh binds to its specific site. (Click to enlarge)

There is an enzyme acetylcholinesterase (AChE), also attached to the muscle wall, which keeps the acetylcholine concentration down to prevent excess contractions i.e. tetany  (Figure 2)

Thus we can first use the wash basin model to simply understand how the input & output of Ach normally influences its concentration (Figure 4). The concentration of ACh in the synaptic space will depend on balance between input (release from nerve vesicle) & output (catabolism by AChE).

We will return to this model in the next blogs on snake venoms to see how venoms may influence these processes by changing the a) input, b) output, or c) binding of ACh to its receptor.

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