Review the steps involved in normal neuromuscular transmission

  • A nerve action potential is transmitted, and the nerve terminal is depolarized.
  • ACh is released from storage vesicles at the nerve terminal. Enough ACh is released to bind 500,000 receptors.
  • ACh molecules bind to the a-subunits of the ACh receptor on the postjunctional membrane, generating a conformational change and opening receptor channels. Receptors do not open unless both a-receptors are occupied by ACh (a basis for the competitive antagonism of nondepolarizing relaxants).
  • Sodium and calcium flow through the open receptor channel generating an end-plate potential.
  • When between 5% and 20% of the receptor channels are open and a threshold potential is reached, a muscle action potential (MAP) is generated.
  • Propagation of the MAP along the muscle membrane leads to muscle contraction.
  • The rapid hydrolysis of ACh by acetylcholinesterase (true cholinesterase) within the synaptic cleft and return of normal ionic gradients return the NMJ to a nondepolarized, resting state, and the ACh receptors are closed.

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