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Physiology 2 > Neurotransmitter System I: Glutamate > Flashcards

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?

A

Magnesium

25
Q

What are the subunit types for Kainate receptors?

A

GluK 1, 2, 3, 4 and 5

26
Q

Which kainate receptors can form homomers or heteromers?

A

GluK 1- 3

27
Q

Which Kainate receptors can only form heteromers with GluK 1-3?

A

GluK 4-5

28
Q

What is required for opening of the kainate ligand gated ion channel?

A

Glutamate binding

29
Q

What are metabotropic glutamate receptors made up of?

A

Large extracellular domain
7 TMDs
Intracellular C terminal domain

30
Q

What are the subtypes of metabotropic glutamate receptors?

A

MGlu 1-8

31
Q

What metabotropic glutamate receptor subtypes are in group I?

A

MGlu 1 and 5

32
Q

What metabotropic glutamate receptor subtypes are in group II?

A

MGlu 2 and 3

33
Q

What metabotropic glutamate receptor subtypes are in group III?

A

MGlu 4, 6, 7 and 8

34
Q

What are the group I metabotropic glutamate receptors coupled to?

A

The Gq/PIP2 receptor pathway

35
Q

What does the Gq/PIP2 receptor pathway lead to?

A

Calcium release

36
Q

What are group I metabotropic glutamate receptors important in?

A

Synaptic plasticity

37
Q

Where are group I metabotropic glutamate receptors predominantly found?

A

Post synaptic

38
Q

What are the group II and III metabotropic glutamate receptors coupled to?

A

Gi/O pathway

39
Q

What does the Gi/O pathway do?

A

Decreases cAMP formation and inhibits neurotransmitter release

40
Q

Where are group II and III metabotropic glutamate receptors predominantly found?

A

Pre-synaptic

41
Q

What do excitatory neurotransmitters lead to?

A

Neuronal membrane depolarisation

42
Q

What do excitatory post synaptic currents represent?

A

The flow of ions and change in current across a post-synaptic membrane

43
Q

What does a change in current across a post-synaptic membrane lead to?

A

The generation of excitatory postsynaptic potentials

44
Q

What does the generation of excitatory postsynaptic potentials increase?

A

The likelihood of firing an action potential

45
Q

What is the difference between excitatory post synaptic currents in NMDA, AMPA and kainate?

A

NMDA and kainate are slower and last longer than those produced by AMPA receptors

46
Q

What is excitotoxicity?

A

Pathological process by which excessive excitatory stimulation can lead to neuronal damage and death

47
Q

What happens if VGLUTs aren’t working properly?

A

Glutamate accumulates in the presynaptic neurone

48
Q

What normally stops glutamate accumulating in the synaptic cleft?

A

EAATs transport glutamate out of the synaptic cleft into the presynaptic neuron down the concentration gradient

49
Q

What happens to EAAT function if there’s a high glutamate concentration in the presynaptic neuron?

A

Starts pumping glutamate into the synaptic cleft

50
Q

What happens if glutamate is pumped into the synaptic cleft?

A

Uncontrolled influx of calcium into the post-synaptic neuron

51
Q

What can uncontrolled influx of calcium into the post-synaptic neuron cause?

A

Mitochondrial damage, oxidative stress and apoptosis

52
Q

What diseases are linked to excitotoxicity?

A

Stroke and Alzheimer’s

53
Q

What is Alzheimer’s?

A

Neurodegenerative disorder

54
Q

What is Alzheimer’s characterised by?

A

Neuronal cell death in the hippocampus and cerebral cortex

55
Q

What is the drug used to treat moderate-severe Alzheimer’s called?

A

Memontine

56
Q

How does memontine work?

A

Low affinity NMDA receptor antagonist that blocks the NMDA receptor ion channel to reduce glutamate excitotoxicity

57
Q

What is long term potentiation?

A

Persistent strengthening of a synapse based upon repeated patterns of activity

58
Q

What does long term potentiation underlie?

A

Learning and memory

Physiology 2 (38 decks)

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