NEUROTRANSMITTER RELEASE

Question 1

How fast do action potentials travel

Answer 1

120 metres/sec

Question 2

What is the location of action potential and where does it follow through to

Answer 2

They trigger at the nerve terminal, a release of neurotransmitters, which carry the signal across the synaptic cleft

Question 3

What happens to the neurotransmitters acting on receptors expresses on the receiving cell

Answer 3

excitation or inhibition

Question 4

What is Ach usually released to?

Answer 4

gamma a receptors

Question 5

What is fast synaptic transmission mediated by

Answer 5

Transmitter-gated ion channels (cys loop superfamily)

Question 6

What is an example of a member of the cys-loop superfamily

Answer 6

Nicotinic acetylcholine receptor

Question 7

Explain the characteristics of the nAChR

Answer 7

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

Question 8

Where is the binding site for the agonist on the nAChR

Answer 8

Ach

Question 9

What are MEPPS

Answer 9

Miniature end plate potentials

Question 10

What is alpha-bungarotoxin?

Answer 10

Aselective high affinity antagonist of the nAChRs

Question 11

Does a mepp result from the release of a single vesicle of packaged ACh?

Answer 11

Yes- this then activates a family of nicotinic receptors where sodium fluxes and causes the depolarisation

Question 12

What does the drug Vesamicol do?

Answer 12

Inhibits vesicular uptake of ACh and consequently decrease the amplitude of mepps (can help with adenocarcinoma in lungs)

Question 13

What does black widow spider venom (a-Latrotoxin-aLTX) affect with neurotransmitter release?

Answer 13

Their venom influences spontaneous transmitter release

1) massive ACh release and muscle spasms
2)Depletion of vesicles, inhibition of endocytosis, distended terminal paralysis

Question 14

How many binding sites are there on the pre-synaptic nerve

Answer 14

2

Question 15

Explain how a-latrotoxin spider venom influences neurotranmitter release

Answer 15

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

Question 16

Where does the release and recycling of synaptic vesicles occur?

Answer 16

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

Question 17

Name each step of the release and recycling

Answer 17

1 Budding
2 Endosome
3 Budding
4 Neurotransmitter uptake into docking
5 Priming
6 Fusion
7 Kiss and run (recycling)

Question 18

What is essential for neurally evoked neurotransmitter release

Answer 18

Calcium

Question 19

How does calcium enter the cell?

Answer 19

Via voltage gated calcium channels

Question 20

What happens when calcium enters the cell?

Answer 20

Calcium triggers vesicle fusion very fast ~0.1ms
Magnesium then blocls the voltage gated calcium ion channel

Question 21

What happens within the muscle is there is no action potentia?

Answer 21

No muscle contraction

Question 22

How do you calculate the quantal content

Answer 22

QC= number of vesicles/stimulus
or
mean EPP amplitude (mV)/ mean MEPP amplitude (mV)

Question 23

What do mepps summate to give?

Answer 23

An end plate potential, which initiates an action potential and causes muscles contraction

Question 24

In the CNS what does the glutamate receptor release in order to produce neuronal excitation

Answer 24

miniature excitatory postsynaptic potentials which summate to produce EPSP

Question 25

What produces neuronal inhibition?

Answer 25

GABAa or glycine receptor which mediates a miniature inhibitory postsynaptic potential (mIPSPs) which summate to produce IPSP

Question 26

What does dendrotoxin to do quantal content

Answer 26

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

Question 27

What is tubocarine and what does it do Does the quantal content change?

Answer 27

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

Question 28

What reduces the quantal content of botulinum and how does it act?

Answer 28

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

Question 29

Explain the relationship of botulinum toxin and neurotransmitter release

Answer 29

1. It attaches to the synapse 2. Enters through endocytosis 3. It then uses the light chain in cytoplasm which acts as a protease 4. Proteolytic cleavage of synaptobrevin Causes neuromuscular paralysis - brekas down proteins and doesnt aloow vesicles to fuse

Question 30

Whta us Synaptobrevin

Answer 30

a vesicle associated membrane protein (VAMP)

Question 31

What forms a complex that are all sensitive to botulinum toxin?

Answer 31

Synaptobrevin, SNAP25, Syntaxin

Question 32

What is the function of synaptobrevin?

Answer 32

- It binds Ca2+ cooperatively and then undergoes a conformational change - Ca2+ dpendant transmitter release is impaired

Question 33

Explain in terms of VAMPS the process of vesicular release

Answer 33

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