Nervous system signalling context
The nervous signalling to skeletal muscle occurs through nicotinic receptors which use acetylcholine. These are quick receptors, which acetylcholine binds to them they let in Na+ ions, leading to action potentials with enough sodium at the neuromuscular junction
overview of nervous system
cns fires to muscles and pns through nicotinic receptors. using ACh
PNS fires to effector organs (symp and parasymp through NE and ACH (musc))
Ionotropic receptors
chemical gated ion channel lets Na+ into cells pentameric and ~20 transmembrane subunits different isoforms of monomers based on tissye muscles has 2 alpha 1 beta 1 gamma 1 delt
Acetylcholine
Acetylcholine is made fo acetyl and choline (shocker) acetylcholine is transported in vesicles and calcium ions trigger the vesicles to merge with memebrane ACH esterase breaks down ACh in the cleft choline is recycled
Drug targets
- Inhibiting ACh release presynaptically (toxins and poisons)
- Inhibiting esterase (toxins and poisons)
- Inhibiting ACh postsynaptically (easiest and best)
Postsynaptic neuromuscular block
mess with Nictotinic receptors either switch them on permanently or off
depolarising vs nondepolarising
competitive antagonist (nondepolarising) or agonist (depolarising)
nondepolarising
something-curaranine tubocuranine (competitive antagonist) also reversable as it is competitive (slow but fast to clear) not absorbed orally quaternary ammonium compound
a lot of ACh gets release and so only
add neostigimine which is a ACh esterase inhibitor to functionally magnify ACh
depolarising
suxamethoium decomethonium (agonist) (fast but long to clear)
overactivates nicotinic receptors.
phase 1 block causes tetanic spasms and then flaccidity as loss of membrane potential decmethonium can be metabolised out
phase 2 block this is bc muscles figure out receptors are damaged and endocytoses receptors so then you have to wait for new receptors