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Flashcards in Mechanisms of exocytosis Deck (34)
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1
Q

What are the 5 different stages to fast synaptic transmission?

A
  1. AP. 2. Ca influx via calcium channels. 3. Vesicular transmitter release. 4. Activation of transmitter-gated ion channels. 5. Activation of voltage-gated ion channels.
2
Q

What mediates fast synaptic transmission?

A

Mediated by transmitter-gated ion channels. eg. nicotinic ACh receptor.

3
Q

Name the 4 important properties of the nicotinic ACh receptor?

A
  1. Intergral ion channel. 2. Agonist binding to the receptor induces a rapid conformational change to open the channel. 3. Selective for certain ions. 4. Signalling is extremely rapid.
4
Q

How do you test for fast synaptic transmission?

A

Record miniature end plate potentials (MEPPS) at the NMJ.

5
Q

Define what a “MEPP” is?

A

Miniature end plate potential. It is the energy given off when one single vesicle package of neurotransmitter is released.

6
Q

What process does the vesicles undergo to release the neurotransmitters from the presynaptic membrane?

A

Exocytosis.

7
Q

What is vesamicol and what does it do?

A

Inhibits vesicular uptake of ACh and consequently decreases the amplitude of MEPPs.

8
Q

Name the 2 ways in which a drug can decrease the amplitude of MEPPs?

A
  1. Inhibiting the post-synpatic receptor. 2. Decreasing the amount of ACh in each vesicle.
9
Q

What way does vesamicol decrease the amplitude of MEPPs?

A

By decreasing the amount of ACh in each vesicle.

10
Q

What does alpha-latrotoxin do?

A

Causes a large ACh release resulting in muscle spasms. Then there is a depletion of vesicles causing paralysis.

11
Q

Define “quantal content”?

A

The amount of neurotransmitter in each vesicle.

12
Q

How are synaptic vesicles recycled?

A

Exocytosis of neurotransmitter, Endocytosis from the membrane to produce new vesicles. Use of endosome to transport neurotransmitters into the vesicles

13
Q

What happens during an AP to synaptic release?

A

Calcium levels increases. Causing an increase in exocytosis- Increase in neurotransmitter release. After AP, low levels of vesicles.

14
Q

Define “EPP”

A

End-plate potential. The energy released taking into account all the vesicles that are released to the end plate.

15
Q

What does nACh receptor do?

A

Uses ACh as an agonist to transport sodium into the cell.

16
Q

What happens to the AP when there is a high magnesium and low calcium extracellular solution?

A

Reduces the EPP to below threshold for firing an AP.

17
Q

What happens to the muscle if there is an AP?

A

Contraction of the muscle.

18
Q

What does it mean when the release of neurotransmitter is quantal?

A

There is an immediate release of ACh and then gradually decreases.

19
Q

What is the equation of the quantal content?

A

Mean EPP (mV) / mean MEPP (mV)

20
Q

What receptor is activated to cause a MEPP?

A

Activation of nicotinic ACh receptors. Each quanta gives rise to this,

21
Q

Define “quanta”?

A

A single vesicle.

22
Q

What does GABAA do?

A

Mediates miniature inhibitory postsynpatic potentials summate to produce an IPSP-> neuronal inhibition.

23
Q

What does dendrotoxin (4-aminopyridine) do?

A

Increase EPP. No change in MEPP. Blocks voltage-gated potassium channels to prolong AP. Increase in calcium influx to increase release.

24
Q

What does tubocurarine do?

A

Decrease in EPP and MEPP Acts postsynaptically to block the nicotinic ACh receptors.

25
Q

What does botulinum toxin do?

A

Decrease quantal content. Decrease EPP but no change in MEPP. Acts post-synpatically to decrease neurally evoked ACh release.

26
Q

Name the 4 different stages in which the botulinum toxin inhibit vesicular release?

A
  1. Attachment of the toxin to the postsynpates. 2. Toxin enters the synapse by endocytosis. 3. Light chain is excreted into the cytoplasm. 4. Proteolytic cleavage of synaptobrevin.
27
Q

Define “synaptobrevin”?

A

A vesicle assocaited membrane protein (VAMP)

28
Q

Name the 4 different parts in how the botulinum toxin binds to the post-synpases?

A

Synaptobrevin. Synaptotagmin. SNAP 25. Syntaxin

29
Q

What part of the binding is Botox B D F G important in?

A

Synaptobrevin.

30
Q

What part of the binding is botox A E important in?

A

SNAP 25.

31
Q

What part of the binding is botox C important in?

A

Syntaxin

32
Q

How does synaptotagmin work?

A

binds to calcium cooperatively and undergoes conformational change.

33
Q

Describe the 3 stages of a vesicle binding to the postsynpatic membrane?

A
  1. Docking: synaptobrevin binds first to syntaxin and SNAP 25. 2. Priming: Synaptotagmin is recruited to the complex. 3. Fusion: Calcium influx triggers fusion and transmitter release.
34
Q

What two types of proteins make up the VAMPs?

A

Synaptotagmin and synaptobrevin.