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The bacterium Clostridium botulinum secretes botulinum toxin, a neurotoxin. The toxin blocks the release of acetylcholine...

The bacterium Clostridium botulinum secretes botulinum toxin, a neurotoxin. The toxin blocks the release of acetylcholine from the axon terminal of a motor neuron. Explain how the toxin binding would change the normal sequence of events at the neuromuscular junction

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Answer #1

NORMAL SEQUENCE OF EVENTS AT NMJ:

  • Acetylcholine is a neurotransmitter, which is produced by parasympathetic nervous system. It acts at Nm nicotinic receptors at muscular junction to cause muscle contraction.  
  • Steps involved are : acetylcholine is produced in the presynaptic nerve terminal and stored there . Acetate from mitochondria and choline from breakdown of ach ( acetylcholine) at synaptic cleft is taken back by presynaptic neuron to form acetylcholine. Then it is stored in synaptic vesicles in the presynaptic nerve terminal.  
  • There is a group of proteins called snare proteins which involve , syntaxin , snap 25 and synaptobrevin , their main function is exocytosis of the vesicles containing ach into synaptic cleft .
  • following a stimulus, calcium ions influx into presynaptic neuron by calcium channels , which causes snare proteins to fuse and cause exocytosis of vesicles containing acetylcholine.
  • Synaptobrevin is found in vesicle wich stores ach and snap25 and syntaxin in presynaptic nerve terminal membranes .
  • This synaptobrevin fuses with syntaxin and synap25 causing fusion of vesicle with membrane and exocytosis of ach .
  • This ach binds with nicotine receptors in post synaptic neuron which then causes muscle contraction.  

ROLE OF BOTILINIUM TOXIN IN ALTERING NORMAL MECHANISMS:

  • Boltulinum is a neurotoxin , it has its effects mainly in the neuromuscular junction , in autonomic ganglia , postganglionic parasympathetic nervous system.  
  • At neuromuscular junction it is taken up by presynaptic neuron by endocytosis , as it reaches the cytoplasm the acidic environment in the terminal activates the botulinum toxin to more active form .
  • This toxin manages to reach the vesicles and cause clevage of synaptobrevin , syntaxin and synas25 .
  • This toxin causes clevage or proteolysis of snare proteins, so vesicles will not be fused with intracellular membrane of presynaptic neuron, and ach release is blocked .
  • Since ach release is blocked , muscle contraction is absent and flaccid pralysis is seen .
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