Botulinum toxin acetylcholine release affected

Mechanism of action. The cellular actions of bot-ulinum toxin at the neuromuscular junction have recently been clarified.84 This toxin is attracted to glycoproteins located on the surface of the presynaptic terminal at the skeletal neuromuscular junction.33 Once attached to the membrane, the toxin enters the presynaptic terminal and inhibits proteins that are needed for acetylcholine release (Figure 13-4).84 Normally, certain proteins help fuse presynaptic vesicles with the inner surface of the presynaptic terminal, thereby allowing the vesicles to release acetylcholine via exocytosis. Botulinum toxin cleaves and destroys these fusion proteins, thus making it impossible for the neuron to release acetylcholine into the synaptic cleft.32,84 Local injection of botulinum toxin into specific muscles will therefore decrease muscle excitation by disrupting synaptic transmission at the neuromuscular junction. The affected muscle will invariably undergo some degree of paresis and subsequent... 

The effects of curare develop rapidly after it enters the body. Victims develop rapid weakness of voluntary muscles followed by paralysis, respiratory failure, and death. The cause is a blockade of nicotinic cholinergic receptors at the neuromuscular junctions in skeletal muscle. Unlike botulinum toxin, release of acetylcholine by the cholinergic nerve terminals is not affected. When curare is present, however, the acetylcholine that is released cannot bind to the receptors because they are reversibly occupied by the curare. As a consequence, nerve-muscle communication fails and paralysis ensues. 

Botulinum toxin is one of several toxins produced by the bacterium Clostridium botulinum. The toxin binds with high affinity to peripheral cholinergic nerve endings, such as those at the neuromuscular junction and in the autonomic nervous system, preventing the release of the neurotransmitter acetylcholine (1). This action at the neuromuscular junction can cause weakness and even paralysis of the muscles supplied by the affected nerves. Sprouting of the terminal nerves eventually results in re-innervation of the muscles and return of function. Doses are measured in mouse units (MU), IMU being the LD50 in Swiss-Webster mice. 

Botulism is a disease caused by ingestion of foods contaminated with Clostridium botulinum (food-borne botulism) or, very rarely, by wound infection (wound botulism) or colonization of the intestinal tract with Clostridium botulinum (infant botulism). The toxins block the release of acetylcholine. Botulism is characterized by generalized muscular weakness, which first affects eye and throat muscles and later extends to all skeletal muscles. Flaccid paralysis can lead to respiratory failure. 

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