Autonomic and NMJ physiology Flashcards
somatic nervous system always sends a signal
from spine to Ach to nicotinic receptor straight to target tissue which is always skeletal tissue.
Always gets a response - specialised.
autonomic nervous system:
the sympathetic nervous system always sends signal
from spine and has to synapse at the ganglion.
it goes along a Ach and then at ganglion to a nicotinic receptor before reaching the target tissue which is either alpha or beta receptors.
may not always have a response - unspecialised.
preganglionic is short, post ganglionic is long.
neurotransmitters noradrenaline and adrenaline are used.
autonomic nervous system:
the parasympathetic nervous system always sends signals from
spine and has to synapse at the ganglion.
it goes along an Ach and then at the ganglion to a nicotinic receptor before reaching the target tissue which has muscarinic receptors.
the autonomic nervous system targets
Cardiac muscle
Smooth muscle
GI neurons
Glands
acetylcholine acts on
cholinergic receptors:
Nicotinic
- N1 acts on ganglia
- N2 acts on NMJ
Muscarinic
- M1 acts on neuronal
- M2 acts on cardiaac and presynaaptic
- M3 acts on smooth muscle glands
noradrenaline and adrenaline act on
adrenergic receptors:
Alpha
A1
A2
Beta
B1 acts on cardiac muscle
B2
B3
cholinergic receptors are either
ionotropic
- with integral ion channel and specific ones are selectively activated by nicotine and so are called nicotinic receptors
muscarinic
- selectively activated by muscarine and so called muscarinic
metabotropic receptors are found
in adrenergic receptors.
so far no known ionotropic adrenergic receptors.
receptors can be split into groups based on
- what g group they are coupled to
- what secondary messenger signals they produce
steps in synaptic transmission that are common to pretty much all neurotransmitters.
- Transmitter is synthesised and packaged into vesicles.
- Na+ action potential evokes Ca2+ dependent exocytosis.
- Triggers Ca2+-dependent exocytosis of pre-packaged vesicles of transmitter
- Transmitter diffuses across cleft and binds to ionotropic and/or metabotropic receptors to evoke postsynaptic response (on the postsynaptic membrane)
- Transmitter also binds to presynaptic autoreceptors which inhibit voltage gated Ca2+ channels and curtail further transmitter release.
- Transmitter is inactivated, usually by uptake into neurones and glia.
- Transmitter is metabolised, usually, within cells.
Ach is a
transmitter
the receptors of ACh are all
nicotinic type but differ for ganglionic and NMJ
released ACh is broken down by
acetylcholinesterase into acetate and choline.
This is taken back up by neurones and recycled into new ACh to package into vesicles.
how could you stop NMJ synapse working so well
- Inhibit choline transporter (eg hemicholinium)
- Block voltage gated Ca2+ channels (eg black widow spider venom)
- Block vesicle fusion (eg botulinium toxins)
- Use non-depolarising nicotinic receptor blockers (eg d-tubocurarine)
- Use depolarising nicotinic receptor blockers (eg succinylcholine)
hemicholinium and NMJ
Inhibit choline transporter
- blocks some
black widow spider venom and NMJ
Block voltage gated Ca2+ channels
- blocks all
botulinium toxins and NMJ
Block vesicle fusion
- blocks all unless locally injected
d-tubocurarine and NMJ
stop ACh activating the postsynaptic nicotinic receptors by using a competitive antagonist
suxamethoneum and NMJ
blocks receptors with an agonist that activates the ion channel and keeps it activated which causes a brief muscle twitching and then paralysis as the voltage gated channels stay in their inactivated (refractory) state.
Has very short lasting action (3-7 minutes)
Twitching stage can cause damage and subsequent pain.
How could you make NMJ synapses work better?
- Prolong the action potential (eg 3,4-aminopyridine)
- Block acetylcholinesterase (eg eserine) so it hangs around in the synaptic cleft for longer
how can you prolong action potential using 3,4-aminopyridine?
- let more Ca2+ out and cause more ACh release making Ca2+ action potential longer
- normally curtailed (restricted) by K+ entering through voltage gated K+ channels (like Na+ release) - blocking then gets more release
Clinical applications for NMJ:
Non-depolarising or depolarising blockers used for paralysis during
- surgical procedures
- electroconvulsive therapy
- controlling spasms in tetanus
Clinical applications for NMJ:
Botulinum toxin used for
- treating muscle spasm
- cosmetic procedures
Clinical applications for NMJ:
Anti-cholinesterases used for
- treating myasthenic syndromes
- reversing action of non-depolarising blockers
- countering botulinum poisoning
