The 4-step process by which botulinum toxin reduces neuromuscular activity: (a) Normally functioning neuromuscular junction; (b) Binding step: The binding of botulinum dichain as the 100-kDa heavy chain binds to the cholinergic site on the cell membrane of the presynaptic cholinergic motor nerve terminal at a neuromuscular junction; (c) Internalization: The invagination of the cell membrane around the toxin molecule produces small endocytic vesicles within the cytoplasm of a motor nerve terminal; (d) Translocation step: Penetration and translocation of the neurotoxin 30-kDa light chain domain across the endosomal membrane of the endocytic vesicle into the cytosol of the motor nerve terminal; Blocking step: The neurotoxin 50-kDa light chain domain impedes the fusion of the acetylcholine vesicles on the inner side of the nerve terminal plasma membrane and the exocytosis of acetylcholine and its release into the synaptic cleft, preventing muscle contraction (Bendetto AV, 1999).

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