The mechanism of action of tetanus toxin: effect on synaptic processes and some particular features of toxin binding by the nervous tissue.

Abstract

1. In experiments involving injection of tetanus toxin into the rat diaphragm it was shown that the toxin, by acting on the presynaptic apparatus, disturbs the neuromuscular transmission. 2. Electron microscopic investigation does not reveal any visible ultrastructural changes in neuromuscular and axosomatic synapses of spinal motoneurons in tetanus intoxication. However, synaptic vesicles accumulate in the axon terminals. 3. Neuraminidase splits off the sialic acid and liberates the toxin from the protagon-tetanus toxin complex. 4. Toxin neutralized by antitoxin is still able to react with protagon. 5. Toxin bound to protagon can be neutralized by antitoxin; when neutralized, the toxin is retained in complex with protagon. Partial neutralization of the toxicity of the protagon-toxin complex is effected by small amounts of antitoxin; complete neutralization of residual toxicity requires comparatively greater amounts of antitoxin. 6. Fragments of antitoxin [F(ab′)2 and Fab′] are more effective for complete neutralization of toxin bound on protagon than the initial JgG-antitoxin. 7. Injections of antitoxin into the cisterna magna during the incubation period and at earlier stages of experimental tetanus ascendens and descendens are more effective than intramuscular, intravenous or intracarotid injections. At later stages of intoxication all ways of antitoxin injection used are ineffective. 8. The tetanus toxin molecule has at least three groupings; one of them is responsible for the binding on its receptor in brain substance, the other for the interaction with antitoxin and the third for tis specific toxic effect.