Week 2- Part 3- Neurotransmitter synthesis, transport, storage and release. Flashcards

1
Q

Where does the AP arrive and what does it trigger?

A

Synaptic button in the presynaptic neuron- triggers the release of neurotransmitter molecules into the synapse.

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2
Q

What does where are NTs made depend on?

How many different synthesis locations are there?

What are the two categories?

A

Differs depending on what NT we are talking about.

Two.

Small molecule NTs + large molecule NTs.

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3
Q

Small molecule NTs:

Give examples of small molecule NTs.

Where are they synthesised and stored?

Where are they packaged?

A

Dopamine, serotonin, glutamate etc.

Synthesised in the synaptic/terminal button- by enzymes-then stored there ready to be released.

Synaptic vesicles.

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4
Q

Large molecule NTs:

Give an example.

Where are they synthesised and transported to?

Where are they packaged?

Give other two examples.

A

Peptides (proteins).

Synthesised (assembled) in the cell body near the nucleus- they need to be transported a long way down the axon to the synaptic buttons in order to be used.

In vesicles.

Endorphins + oxytocin.

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5
Q

Are large molecule NT the only ones that need a transport system?

Explain how this is relevant to small molecule NTs.

A

No.

Small molecule NTs are made in the synaptic button- but- synthesised by enzymes- enzymes are proteins made in the cell body- enzymes need to be transported down the axon to the terminal button so they can do their jobs.

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6
Q

In the axon of a neuron, what do you have?

What does it include?

What about in the case of small molecule NTs?

What do enzymes do?

A

Cytoskeleton- skeleton of a cell.

Microtubules- like train tracks- they run down the axon and are used to transport packages from the nucleus down to the terminal button.

Enzymes needed to make them- synthesised in the cell body- these enzymes are transported slowly down the axon into the terminal button- then they manufacture neurotransmitter molecules like serotonin- these get packaged into vesicles and stored ready to be released.

Hang about there so they can keep doing their job.

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7
Q

What is synthesised in the cell body too?

Where are they then transported down more rapidly than enzymes?

Where do they go after this?

What happens to the vesicles containing peptide NTs?

What is the process of transporting stuff down an axon called?

A

Peptide NTs.

The axon.

Down microtubule tracks.

Hang around in the button ready to be used.

Axonal/axoplasmic transport.

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8
Q

How many systems do we have?

Give some information about the slow system.

Give some information about the fast system.

What happens if the axon is full of packages?

A

Two- the slow + fast system.

2-8 mm/day- for things like e.g. enzymes- Microfilaments.

200-400mm/day- peptide neurotransmitters + membrane proteins (in vesicles)- might still take a couple of days.

Vesicles, carrying proteins, will always be some arriving at the end of the axon- won’t run out.

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9
Q

How do they get moved along the axon, what powers this motion?

What does it depend on?

What provides track?

What moves materials (packages) along the tracts?

A

Axoplasmic transport.

Elements of the cytoskeleton.

Microtubules and neurofilaments provide track.

Motor proteins.

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10
Q

What moves vesicles?

What is the most well-known one?

What is another one?

Give an example of an actin filament motors.

A

Microtubule motors.

Kinesin- anterograde movement- down the axon, away from the cell body to the synaptic button.

Dynein- retrograde movement.

Myosin.

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11
Q

Why is axonal transport is important?

What is it?

What does this loss do?

A

Has clinical relevance.

Reduction in number + density of microtubules- feature of some neurodegenerative diseases (e.g. Alzheimer’s).

Impairs the capacity of the neuron to maintain axonal transport and synaptic connections- if they cannot get get packages of enzymes, peptide neurotransmitters etc to synaptic buttons, it cannot function effectively.

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12
Q

How do synaptic vesicles get released into the synapse?

What then happens to these vesicles?

A

AP arriving at the presynaptic neurons terminal button- triggers the release of neurotransmitter molecules into synapse- through a process called exocytosis (exo= moving something from the interior to the exterior in this case neurotransmitter molecules).

They fuse with the cell membrane and release their contents into the synaptic cleft- all through exocytosis.

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13
Q

In terms of the chemical processes involved, what triggers this?

What then happens after this?

A

When the AP arrives at the synaptic button- causes the opening of a voltage gated calcium channel.

Positively charged calcium ions rush into the presynaptic cell- these trigger the fusion of the synaptic vesicles with the cell membrane- happens through exocytosis.

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14
Q

What happens when the NT molecules diffuse across the synapse?

What do the vesicles have?

What is the thing that is outside the vesicle called?

How does it work?

A

They bind to receptors in the postsynaptic membrane- they will do stuff, either excite or inhibit what that neuron is doing.

Proteins projecting from the outside.

Snare proteins- designed to snag on parts of the cell membrane.

There is a synaptic vesicle- snare proteins catching on the cell membrane- fuse with the cell membrane- release its contents into the synaptic cleft.

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15
Q

How many vesicles get released into the synapse?

What happens at the peripheral nervous system?

What might a single action potential trigger?

A

Varies depending on the type of neuron we are speaking about.

At at neuromuscular junctions- neurons + synapse with muscle cells- stimulate to contract- movement depends on this.

Exocytosis of 200+ vesicles at a neuromuscular synapse.

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16
Q

In the CNS, what might a single action potential trigger?

What might happen if it is alone?

What will you need?

A

Might trigger the exocytosis of one vesicle from the presynaptic neuron.

Might only cause an EPSP of 0.2 to 0.3 mV- not enough to get the postsynaptic neuron to fire.

Many vesicles to trigger a postsynaptic neuron (e.g. get it to -65mV)- many to release enough NT molecules- to stimulate a postsynaptic neuron sufficiently to reach excitation- happens through summation.

17
Q

Explain the whole process, first 4 steps- look at the picture in the doc first.

A

1) AP- down the axon of the presynaptic neuron- into the presynaptic button.
2) Causes depolarization- opens voltage gated calcium channels- positively charged calcium ions rush into the synaptic button.
3) Triggers fusion of the synaptic vesicles with the cell membrane.
4) Fusion depends on- snare proteins snagging the membrane causing fusion.

18
Q

Continue explaining the process- last 4 steps.

A

5) NT molecules get released into the synapse through the exocytosis process.
6) Go across the postsynaptic cell and do stuff- cause ion channels to open- bind to receptors- can cause an excitatory or inhibitory postsynaptic potential.
7) Then postsynaptic neuron might fire or not.
8) Vesicles can get recycled and used again.

19
Q

Termination of synaptic transmission:

What is this avoiding?

What are the two mechanisms to terminate activity?

A

Continual action of the postsynaptic neuron.

1) Reuptake- pumped back into the presynaptic neuron to be used again- are selective to particular neurotransmitters + a well known one is SSRIs- are packaged up into vesicles to be reused.
2) Enzymatic degradation- get broken down by enzymes in the synapse.

20
Q

What are all the steps we learnt about interesting?

A

Because they are all steps drugs can influence- like influencing the synthesis of NTs or disrupting how they are stored.