Neurotransmitter System I: Glutamate Flashcards

1
Q

What are the criteria for a neurotransmitter?

A

Synthesised and stored in the pre-synaptic neuron
Release by a presynaptic axon terminal upon stimulation
Produce a response in the post-synaptic cell

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2
Q

What is glutamate?

A

major excitatory neurotransmitter in the CNS

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3
Q

What do over half of all the brain synapses release?

A

Glutamate

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4
Q

What is glutamate synthesised from, and using what enzyme?

A

Glutamine, using glutaminase

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5
Q

Where is glutamate synthesised?

A

Nerve terminals

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6
Q

How is glutamate transported into vesicles?

A

Counter transport with H+ ions using VGLUTs

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7
Q

How is glutamate retaken up?

A

Sodium ion dependant excitatory amino acid transporters

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8
Q

What enzyme degrades glutamate?

A

Glutamine synthase

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9
Q

How is glutamine transported out of the glial cell and into the neurons?

A

SN1 and SAT2 transporters

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10
Q

What are the ionotropic glutamate receptors?

A

AMPA, NMDA, Kainate

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11
Q

What are the metabotropic glutamate receptors?

A

Group I, II and III

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12
Q

What do NMDA receptors allow the entry of?

A

Both sodium and calcium ions

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13
Q

What do AMPA and Kainate receptors allow the entry of?

A

Sodium

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14
Q

What do AMPA, NMDA and kainate receptors allow out?

A

Potassium

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15
Q

What are the four AMPA receptor subunit types?

A

GluA 1, 2, 3 and 4

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16
Q

What is the most common makeup of an AMPA receptor?

A

Two GluA 2 subunits and two GluA 1, 3, or 4

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17
Q

How many binding sites does the AMPA receptor have?

A

Four

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18
Q

How many binding sites must be occupied for AMPA channel opening?

A

Two

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19
Q

What prevents calcium ion flow in AMPA receptors?

A

GluA2 subunit

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20
Q

What are the subunit types for NMDA?

A

GluN 1, 2 and 3

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21
Q

What is the most common NMDA structure?

A

Two GluN1 and two GluN2

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22
Q

What is special about GluN3 subunits?

A

Nonfunctional and therefore inhibitory to NMDA receptor function

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23
Q

Are the NMDA receptors ligand or voltage gated?

A

Both

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24
Q

What blocks the voltage gated NMDA channels at resting membrane potential?

25
What are the subunit types for Kainate receptors?
GluK 1, 2, 3, 4 and 5
26
Which kainate receptors can form homomers or heteromers?
GluK 1- 3
27
Which Kainate receptors can only form heteromers with GluK 1-3?
GluK 4-5
28
What is required for opening of the kainate ligand gated ion channel?
Glutamate binding
29
What are metabotropic glutamate receptors made up of?
Large extracellular domain 7 TMDs Intracellular C terminal domain
30
What are the subtypes of metabotropic glutamate receptors?
MGlu 1-8
31
What metabotropic glutamate receptor subtypes are in group I?
MGlu 1 and 5
32
What metabotropic glutamate receptor subtypes are in group II?
MGlu 2 and 3
33
What metabotropic glutamate receptor subtypes are in group III?
MGlu 4, 6, 7 and 8
34
What are the group I metabotropic glutamate receptors coupled to?
The Gq/PIP2 receptor pathway
35
What does the Gq/PIP2 receptor pathway lead to?
Calcium release
36
What are group I metabotropic glutamate receptors important in?
Synaptic plasticity
37
Where are group I metabotropic glutamate receptors predominantly found?
Post synaptic
38
What are the group II and III metabotropic glutamate receptors coupled to?
Gi/O pathway
39
What does the Gi/O pathway do?
Decreases cAMP formation and inhibits neurotransmitter release
40
Where are group II and III metabotropic glutamate receptors predominantly found?
Pre-synaptic
41
What do excitatory neurotransmitters lead to?
Neuronal membrane depolarisation
42
What do excitatory post synaptic currents represent?
The flow of ions and change in current across a post-synaptic membrane
43
What does a change in current across a post-synaptic membrane lead to?
The generation of excitatory postsynaptic potentials
44
What does the generation of excitatory postsynaptic potentials increase?
The likelihood of firing an action potential
45
What is the difference between excitatory post synaptic currents in NMDA, AMPA and kainate?
NMDA and kainate are slower and last longer than those produced by AMPA receptors
46
What is excitotoxicity?
Pathological process by which excessive excitatory stimulation can lead to neuronal damage and death
47
What happens if VGLUTs aren't working properly?
Glutamate accumulates in the presynaptic neurone
48
What normally stops glutamate accumulating in the synaptic cleft?
EAATs transport glutamate out of the synaptic cleft into the presynaptic neuron down the concentration gradient
49
What happens to EAAT function if there's a high glutamate concentration in the presynaptic neuron?
Starts pumping glutamate into the synaptic cleft
50
What happens if glutamate is pumped into the synaptic cleft?
Uncontrolled influx of calcium into the post-synaptic neuron
51
What can uncontrolled influx of calcium into the post-synaptic neuron cause?
Mitochondrial damage, oxidative stress and apoptosis
52
What diseases are linked to excitotoxicity?
Stroke and Alzheimer's
53
What is Alzheimer's?
Neurodegenerative disorder
54
What is Alzheimer's characterised by?
Neuronal cell death in the hippocampus and cerebral cortex
55
What is the drug used to treat moderate-severe Alzheimer's called?
Memontine
56
How does memontine work?
Low affinity NMDA receptor antagonist that blocks the NMDA receptor ion channel to reduce glutamate excitotoxicity
57
What is long term potentiation?
Persistent strengthening of a synapse based upon repeated patterns of activity
58
What does long term potentiation underlie?
Learning and memory