Acetylcholinesterase AChE

The bond between ACh and its receptor protein exists for only a brief instant. The ACh-receptor complex quickly dissociates but can be quickly re-formed as long as free ACh is in the vicinity. In order for activity in the postsynaptic cell to be stopped, free ACh must be inactivated very soon after it is released. The inactivation of ACh is achieved by means of an enzyme called acetyl-cholinesterase, or AChE, which is present on the postsynaptic membrane or immediately outside the membrane, with its active site facing the synaptic cleft (fig. 7.25).

Presynaptic axon

Postsynaptic cell

Postsynaptic cell

■ Figure 7.25 The action of acetylcholinesterase (AChE). The AChE in the postsynaptic cell membrane inactivates the ACh released into the synaptic cleft. This prevents continued stimulation of the postsynaptic cell unless more ACh is released by the axon.

Nerve gas exerts its odious effects by inhibiting AChE in skeletal muscles. Since ACh is not degraded, it can continue to combine with receptor proteins and can continue to stimulate the postsynaptic cell, leading to spastic paralysis. Clinically, cholinesterase inhibitors (such as neostigmine) are used to enhance the effects of ACh on muscle contraction when neuromuscular transmission is weak, as in the disease myasthenia gravis.

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