NEUROTRANSMITTER RELEASE Flashcards
How fast do action potentials travel
120 metres/sec
What is the location of action potential and where does it follow through to
They trigger at the nerve terminal, a release of neurotransmitters, which carry the signal across the synaptic cleft
What happens to the neurotransmitters acting on receptors expresses on the receiving cell
excitation or inhibition
What is Ach usually released to?
gamma a receptors
What is fast synaptic transmission mediated by
Transmitter-gated ion channels (cys loop superfamily)
What is an example of a member of the cys-loop superfamily
Nicotinic acetylcholine receptor
Explain the characteristics of the nAChR
Integral ion channel
Agonist bidning to the receptor induces a rapid conformational change to opent he channel
The channel is selective foe certain ions
Signalling is extremely rapid
Where is the binding site for the agonist on the nAChR
Ach
What are MEPPS
Miniature end plate potentials
What is alpha-bungarotoxin?
Aselective high affinity antagonist of the nAChRs
Does a mepp result from the release of a single vesicle of packaged ACh?
Yes- this then activates a family of nicotinic receptors where sodium fluxes and causes the depolarisation
What does the drug Vesamicol do?
Inhibits vesicular uptake of ACh and consequently decrease the amplitude of mepps (can help with adenocarcinoma in lungs)
What does black widow spider venom (a-Latrotoxin-aLTX) affect with neurotransmitter release?
Their venom influences spontaneous transmitter release
1) massive ACh release and muscle spasms
2)Depletion of vesicles, inhibition of endocytosis, distended terminal paralysis
How many binding sites are there on the pre-synaptic nerve
2
Explain how a-latrotoxin spider venom influences neurotranmitter release
Involves both the Ca2+ dependant and Ca2+ independant pathways
a-LTX binds to a specific presynaptic receptors (neurexin and latrophillin) - G-protein coupled receptor
Toxin forms a cation
Where does the release and recycling of synaptic vesicles occur?
Starts at the endosomes, calcium then enters and fused with presynaptic membrane - exocytosis
There is then the release of neurotransmitter
Vesicle goes up and gets refilled or goes through a long process of being coated in clathrin
Name each step of the release and recycling
1 Budding
2 Endosome
3 Budding
4 Neurotransmitter uptake into docking
5 Priming
6 Fusion
7 Kiss and run (recycling)
What is essential for neurally evoked neurotransmitter release
Calcium
How does calcium enter the cell?
Via voltage gated calcium channels
What happens when calcium enters the cell?
Calcium triggers vesicle fusion very fast ~0.1ms
Magnesium then blocls the voltage gated calcium ion channel
What happens within the muscle is there is no action potentia?
No muscle contraction
How do you calculate the quantal content
QC= number of vesicles/stimulus
or
mean EPP amplitude (mV)/ mean MEPP amplitude (mV)
What do mepps summate to give?
An end plate potential, which initiates an action potential and causes muscles contraction
In the CNS what does the glutamate receptor release in order to produce neuronal excitation
miniature excitatory postsynaptic potentials which summate to produce EPSP
What produces neuronal inhibition?
GABAa or glycine receptor which mediates a miniature inhibitory postsynaptic potential (mIPSPs) which summate to produce IPSP
What does dendrotoxin to do quantal content
Increases it- EPP is increased and MEPP is not changed therefore quantal content is up
Does this by blocking K+ channels and prolonging the action potential. This gives an increased opportunity to open calcium channels and vesicles being released
What is tubocarine and what does it do
Does the quantal content change?
A non-depolarising neuromuscular blocker - acts postsynaptically
Reduces the amplitude of the endplate potential (e.p.p) to below the threshold for muscle fibre action potential generation
Quantal content does not change as both EPP and MEPP are reduced
What reduces the quantal content of botulinum and how does it act?
EPP is reduced whilst there is no change in MEPPs
Acts pre-synaptically to decrease neurally evoked ACh release - has no effect on the amount of ACh in each vesicle - no effect on quantal size
no effect on the postsynaptic nicotinic receptors
Explain the relationship of botulinum toxin and neurotransmitter release
- It attaches to the synapse
- Enters through endocytosis
- It then uses the light chain in cytoplasm which acts as a protease
- Proteolytic cleavage of synaptobrevin
Causes neuromuscular paralysis - brekas down proteins and doesnt aloow vesicles to fuse
Whta us Synaptobrevin
a vesicle associated membrane protein (VAMP)
What forms a complex that are all sensitive to botulinum toxin?
Synaptobrevin, SNAP25, Syntaxin
What is the function of synaptobrevin?
- It binds Ca2+ cooperatively and then undergoes a conformational change
- Ca2+ dpendant transmitter release is impaired
Explain in terms of VAMPS the process of vesicular release
1 Docking- complex of VAMP proteins and SNAP25 forms to bring the vesicle into the active zone adjacent to the calcium channel
2 Priming- Synaptotagmin is recruited to the complex
3 Fusion- calcium influx triggers fusion and transmitter release
