Post-synaptic toxins

Sellin, L.C., Thesleff, S. (1981). Pre- and post-synaptic actions of botulinum toxin at the rat neuromuscular junction. J. Physiol. 317 487-95. 

In our laboratory we first isolated the major lethal protein (termed Cobrotoxin) of non-enzymatic nature from the venom of Taiwan cobra Naja naja atra) in 1964 and subsequently purified and crystallized the protein. The primary structure and the disulfide linkages with various efforts by chemical modification and immunological methods in elucidation of the structure-function relationship of this important venom neurotoxin have since been accomplished. Structure-activity correlations have been drawn from chemical modification carried out on both pre- and post-synaptic neurotoxins. With recent advances in DNA recombination and protein engineering, we feel that the time is now ripe to apply these techniques to the isolation and characterization of the genes encoding these toxins. Detailed structural and site-specific mutational studies on the cDNA clones of neurotoxins of both types may complement our previous chemical modifications of the functional role of some amino acid residues in neurotoxins and lead to insight into the modes of action for these biologically active molecules. 

There are a number of strains of BoTx. They act by preventing the formation of vesicles containing ACh which leads to reduced release. This in turn means that insufficient ACh is released with the arrival of a nerve impulse to ensure that a post-junctional electric impulse will be generated and therefore synaptic transmission becomes blocked. The most striking consequence of this is a descending neuromuscular paralysis which may be life-threatening due to the effects on the respiratory muscles. At the autonomic level, prodromal symptoms such as dry mouth are related to synaptic block. The toxidromes produced by BoTx are considered in Chap. 7. The most important clinical consequence of the pathophysiology of the toxin is the production of a potentially fatal respiratory failure and arrest. More information about BoTx will be found in Chap. 11. 

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