The Neuromuscular Junction Flashcards
What does acetyl transferase enzyme do?
It transfers and acetyl group to choline to form acetylcholine
What effect does Ca2+ and Mg2+ have on synaptic transmission?
Ca2+ will stimulate excocytosis of the neurotransmitter from vesicle and Mg2+ will inhibit it
What is the mechanism of Hemicholinium?
Hemicholinium is an uptake inhibitor, working by competitive inhibition. It is preferential towards highly active synapses
What is the difference in location between AChE and BuChE?
AChE is membrane bound and fount within cholinergic synapses and in red cells. BuChE is soluble and is found in plasma, liver, and many other tissues.
What is the difference in specificity between AChE and BuChE?
AChE is specific to ACh and closely related esters whilst BuChE is less specific
What is the dibucaine number and what does it show?
Some people have a mutation in the BuChE enzyme, which makes them more sensitive to anaesthetics such as suxamethonium. Dibucaine inhibits BuChE, so with a mutation in BuChE the dibucaine number will be lower.
Describe the hydrolysis of ACh by acetylcholinesterase
AChE has an anionic site which attracts the cationic head ionically, and a esteratic site with a serine hydroxyl group that interacts with ester. Hydrolysis occurs in which:
- ACh binds to the enzyme at the two sites
- Acetyl group binds to serine OH in esteratic site, resulting in transiently acetylated enzyme and free dissociated choline.
- Hydrolysis of acetyl-OH bond releasing the acetyl group.
Give 3 examples of Ca2+ channel blockers in the NMJ
Botulinum toxin, tetanus toxin, aminoglycosides
Competitive vs. depolarising blocker - Myasthenia patients
Myasthenia gravis is more sensitive to competitive blockers and cause more damage. Less sensitive to depolarizing blockers because they have less functioning ACh receptors.
Competitive vs. depolarising blocker - hypotension
Competitive blockers cause hypotension because they result in ganglion block and histamine release. Suxamethonium is not hypotensive but can induce bradycardia (agonist action at mAChRs)
Competitive vs. depolarising blocker - Plasma [K+]
Depolarizing blockers will cause hyperkalaemia because of action on endplate causing K+ release from cells. This can be hazardous in burn/crash victims causing cardiac dysrhythmias where it is already enhanced. Competitive blockers do not have any affect on plasma [K+].
Competitive vs. depolarising blocker - Eye
Depolarizing blockers is more sensitive within the eye because the muscles in the eye are much more fine.
What happens to our symptoms when you increase the dose of nicotine?
At low doses it will have central stimulatory effects.
At higher doses it will stimulate ganglia
At highest doses it will block the ganglia and the CNS in a similar manner to a depolarizing block.
Name an example of a short acting reversible anticholinesterase and how does it work?
These cholinesterases only act on anionic site and bind/dissociate rapidly. There is simple reversible competition at the anionic site used in diagnosis of myasthenia gravis. An example is edrophonium.
Name an example of a medium acting reversible anticholinesterase and how does it work?
Neostigmine, physostigmine, pyridostigmine
These bind to both anionic and esteric site. The esteratic bond with serine OH will cause carbamylation. Hydrolysiss of this bond is much slower than usual splitting of acetylated enzyme so each enzyme molecule is inhibited for several minutes. Used therapeutically for myasthenia gravis.
