<P> Transport to the CNS inhibitory interneurons begins with the B - chain mediating the neurospecific binding of TeNT to the nerve terminal membrane . It binds to GT1b polysialo gangliosides, similarly to the botulinum neurotoxin . It also binds to another poorly characterized GPI anchored protein receptor more specific to TeNT . Both the ganglioside and the GPI anchored protein are located in lipid microdomains and both are requisite for specific TeNT binding . Once it is bound the neurotoxin is then endocytosed into the nerve and begins to travel through the axon to the spinal neurons . The next step, transcytosis from the axon into the CNS inhibitory interneuron, is one of the least understood parts of TeNT action . At least two pathways are involved, one that relies on the recycling of synaptic vesicle 2 (SV2) system and one that does not . </P> <P> Once the vesicle is in the inhibitory interneuron its translocation is mediated by pH and temperature, specifically a low or acidic pH in the vesicle and standard physiological temperatures . Once the toxin has been translocated into the cytosol the disulfide bond is reduced, mainly by the NADPH - thioredoxin reductase - thioredoxin redox system and the light chain is free to cleave the Gln76 - Phe77 bond of synaptobrevin . Cleavage of synaptobrevin affects the stability of the SNARE core by restricting it from entering the low energy conformation which is the target for NSF binding . Synaptobrevin is an integral V - SNARE necessary for vesicle fusion to membranes . The cleavage of synaptobrevin is the final target of TeNT and even in low doses the neurotoxin will inhibit neurotransmitter exocytosis in the inhibitory interneurons . The blockage of these neurotransmitters is what causes the physiological effects that accompany TeNT, specifically the blockage of the neurotransmitters GABA and glycine . </P> <P> Tetanus toxin causes violent spastic paralysis by blocking the release of γ - aminobutyric acid (GABA). GABA is a neurotransmitter that inhibits motor neurons . </P> <P> The action of the A-chain stops the affected neurons from releasing the inhibitory neurotransmitters GABA and glycine, but also excitatory transmitters, by degrading the protein synaptobrevin 2 . The consequence of this is dangerous overactivity in the muscles from the smallest stimulus--the failure of inhibition of motor reflexes by sensory stimulation . This causes generalized contractions of the agonist and antagonist musculature, termed a tetanic spasm . </P>

Tetanospasmin has this effect on the neuromuscular junction