Nerves cannot supply enough choline so it has to be taken up from the blood. We get it from our diet or synthesis in the liver and then released into the circulation to be used in other parts of the body
To get choline into the nerve terminals, a secondary active transporter is used because it uses the gradient of another ion (Na+) to drive choline into the terminal.
Hemicholinium is a competitive inhibitor that prevents choline from binding to the necessary site on the transporter. This means that eventually the nerve terminal will be unable to transmit acetylcholine has the stores have been depleted
1 of 6
Synthesis
Choline + acetylCoA ==> acetylcholine + CoA
Catalysed by choline acetyltransferase (ChAT), found in the cytoplasm of nerve terminals
ChAT has another substrate ==> Triethylcholine. So if there is a high concentration of triethylcholine, the amount of ACh synthesised will decrease
2 of 6
Storage
An ATPase moves acetylcholine up its concentration gradient from the cytoplasm into the vesicles
A vesicular ACh transporter pumps ACh into the vesicles
Acetyltriethylcholine is a substrate for the vesicular ACh transporter. If it's available it's also packaged into vesicles; when it's released by exocytosis it acts as a "false transmitter" (the nerve terminals are using it as a neurotransmitter though its effects as an agonist of the post-synaptic receptors [muscarinic receptors] are weak)
3 of 6
Release
Neurotransmitter release requires Ca2+ ions to enter into the nerve terminals, vesicles fuse with plasma membrane and release contents into extracellular space (exocytosis)
A toxin can cause a massive release and depletion of vesicles (α-latrotoxin); this will cause spasming of muscles.
Botulinum toxin (botox) can be used to block neurotransmitter release.
4 of 6
Inactivation
Acetylcholinesterase breaks acetylcholine down into acetate and choline (non-reversible). This is much faster than diffusion alone
Neostigmine is an inhibitor of acetylcholinesterase, stop this break down and amplify effects of parasympathetic nervous system
5 of 6
Feedback
When ACh is exocytosed, it can act on the muscarinic receptors on the nerve terminal it was in before. This can inhibit exocytosis
ATP can also be released by the vesicles, and then broken down in the extracellular space into adenosine which acts on its own receptors. This also inhibits neurotransmitter release
This is useful because it stops overstimulation of nerves as they can "switch themselves off" and stop further release of neurotransmitters
Comments
No comments have yet been made