Inactivation of Released Acetylcholine

We have seen how ACh is released from the synaptic terminal and how it depolarizes the postsynaptic muscle cell. How is the action of ACh terminated so that the end-plate region returns to its resting state? The answer is that there is another specialized ACh-binding protein in the end-plate region. This protein is the enzyme acetylcholinesterase, which splits ACh into acetate and choline. Because neither acetate nor choline can bind to and activate the ACh-activated channel, the acetylcholinesterase effectively halts the action of any ACh it encounters.

When a puff of ACh is released in response to an action potential in the syn-aptic terminal, the concentration of ACh in the synaptic cleft abruptly rises. Some of the released ACh molecules will bind to ACh-activated channels, causing them to open and increasing the sodium and potassium permeability of the end-plate membrane; other ACh molecules will bind to acetylcholin-esterase and be inactivated. Even though the binding of ACh to the post-synaptic channel is highly specific, it is readily reversible; the binding typically lasts for only about 1 msec. When an ACh molecule comes off a gate, the channel closes. The newly freed ACh molecule may then bind again to an ACh-activated channel, or it might bind to acetylcholinesterase and be inactivated. With time following release of the puff, the concentration of ACh in the cleft will fall until all of the released ACh has been split into acetate and choline.

It would be wasteful if the choline resulting from inactivation of ACh were lost and had to be replaced with fresh choline from inside the presynaptic cell. This potential waste is avoided because most of the choline is taken back up into the synaptic terminal, where it is reassembled into ACh by the enzyme choline acetyltransferase. Thus, both the vesicle membrane (the packaging material of the quantum) and the released neurotransmitter (the contents of the quantum) are effectively recycled by the presynaptic terminal.

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