structural:expansion, information:extraction
Pathophysiology

Tetanus neurotoxin (TeNT) binds to the presynaptic membrane of the neuromuscular junction, is internalized, and is transported back through the axon until it reaches the central nervous system. Here, it selectively binds to and is transported into inhibitory neurons via endocytosis. It then leaves the vesicle for the neuron cytosol, where it cleaves vesicle associated membrane protein (VAMP) synaptobrevin, which is necessary for membrane fusion of small synaptic vesicles (SSV's). SSV's carry neurotransmitter to the membrane for release, so inhibition of this process blocks neurotransmitter release.

Tetanus toxin specifically blocks the release of the neurotransmitters GABA and glycine from inhibitory neurons. These neurotransmitters keep overactive motor neurons from firing, and also play a role in the relaxation of muscles after contraction. When inhibitory neurons are unable to release their neurotransmitters, motor neurons fire out of control, and muscles have difficulty relaxing. This causes the muscle spasms and spastic paralysis seen in tetanus infection.

The tetanus toxin, tetanospasmin, is made up of a heavy chain and a light chain. There are three domains, each of which contributes to the pathophysiology of the toxin. The heavy chain has two of the domains. The N-terminal side of the heavy chain helps with membrane translocation, and the C-terminal side helps the toxin locate the specific receptor site on the correct neuron. The light chain domain cleaves the VAMP protein once it arrives in the inhibitory neuron cytosol.

There are four main steps in tetanus's mechanism of action: binding to the neuron, internalization of the toxin, membrane translocation, and cleavage of the target VAMP.