Somatic Flashcards
single neurone connecting the… to the …
CNS, skeletal muscle
what receptors are found skeletal-muscle motor end plates?
nicotinic
2 features about nicotinic receptors at the motor-end-plate
ligand gated ion channels, ACh binds at 2 places
Na+ driven AP open up…
L-type Ca channels
3 ways drugs interfere with ACh release at the NMJ
Block nAChR at NMJ, Decrease ACh at NMJ (inhibit synthesis/release) and Increase ACh or ACh effect at the NMJ
how do NMJ blocking drugs work?
interfere with postsynaptic action of ACh
2 different types of NMJ blocking drugs
NON-depolarising agents and DEPOLARISING agents
how do non-depolarising agents work?
competitive antagonists at the ACh receptors
examples of non-depolarising drugs
d-Tubocurarine, atracurium, α-bungarotoxin
are non-depolarising drugs reversible?
yes, increase [ACh]
unwanted effects of non-depolarising agents
hypotension
how do depolarising agents work?
initially bind and activate the nicotinic receptors, and maintain a constant depolarisation at the end-plate, causing a loss of electrical excitability
example of a depolarising agent
suxamethonium
what is a side effect of the depolarising agents
initial fasciculation
2 main stages of a depolarising agent
muscle held in depolarised state, desensitisation due to persistent stimulation
neostigmine
competes with ACh on cholinesterase, causes parasympathetic stimulation and reverses non-depolarising block
competitive inhibitor of choline uptake
hemicholinium (this will decrease the amount of ACh at the NMJ)
inhibition of ACh transport
Vesamicol, blocks ACh transport into vesicles, so can’t be released
False transmitters
triethylcholine - no depolarising actions
block neuronal depolarisation
tetrodotoxin, blocks voltage gated Na+ channels, block AP
Block neuronal Ca2+ influx
streptomycin/neomycin
inhibition of vesicular fusion
botulinum toxin, β bungarotoxin, cleaves the SNARE proteins
6 ways to decrease ACh at NMJ
inhibition of ACh synthesis, inhibition of ACh transport, false transmitters, block neuronal depolarisation, block neuronal Ca influx, inhibition of vesicular fusion
2 methods for increasing ACh release and levels at the NMJ
δ-atrocotoxin - prolong neuronal Na+ channel opening, prolonging the AP AND Acetylcholinesterase inhbitors, so
ACh is not degraded (Edrophonium and Neostigmine)
pralidoxime
can reactivate cholinesterases
neostigmine
improve muscle contraction, used to treat myasthenia gravis
