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Neurology > Glutamate (FS - Week 2) > Flashcards

Glutamate (FS - Week 2) Flashcards

1
Q

What type of neurotransmitter is glutamate

A

excitatory

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2
Q

Where is glutamate synthesised?

A

in the nerve terminals

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3
Q

What is the name of the enzyme that converts glutamine to glutamate?

A

Glutaminase

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4
Q

What is the name of the transporter that transports glutamate into vesicles?

A

VGLUT

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5
Q

What is the name of the transporter that reuptakes glutamate into neurons and glial cells

A

EAAT

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6
Q

What is the name of the enzyme that degrades glutamate to glutamine

A

glutamine synthase

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7
Q

What is the name of the transporter on Glial cells?

A

SN1

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8
Q

What is the name of transporters on neurons?

A

SAT2

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9
Q

Name the 3 ionotropic glutamate receptors

A
  • AMPA receptors
  • NMDA receptors
  • Kainate receptors
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10
Q

Name the 3 metabotropic glutamate receptors

A
  • Group I
  • Group II
  • Group III
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11
Q

How is the NMDA receptor different in terms of influx of ions to the AMPA and Kainate receptors?

A
  • it allows the influx of Na+ and Ca2+ whereas the AMPA receptor only allows Na+ influx
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12
Q

How many subtypes of AMPA receptors are there?

A

4

  • GluA1
  • GluA2
  • GluA3
  • GluA4
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13
Q

How many binding sites are there on the AMPA receptor?

A

4

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14
Q

How many sites of the AMPA receptor need to be occupied for the channel to open?

A

2

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15
Q

What subtype stops the influx of Ca2+ and what does this prevent?

A

GluA2

prevents excitotoxicity

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16
Q

How many subunit types are there of the NMDA receptor

A
  • GluN1
  • GluN2
  • GluN3
17
Q

What is the typical composition of an NMDA receptor

A

2 GluN1 and 2 GluN2/3

18
Q

What subtype is inhibitory in the NMDA receptor function

A

GluN3

19
Q

Apart from influx of ions, what makes the NMDA receptor different to the other glutamate receptors?

A

ligand-gated ion channel and a voltage-gated ion channel

20
Q

What subunits does glutamate bind to on the NMDA receptor

A

GluN2

21
Q

How many subtypes of the Kainate receptor are there?

A

5

- GluK1 > 5

22
Q

How many subtypes of metabotropic glutamate receptors are there?

A

8

mGlu1-8

23
Q

Describe 3 features of the group 1 metabotropic receptors

A
  • located post synaptically
  • Gq coupled = increase in Ca2+
  • include subtypes mGlu1 and mGlu5
24
Q

Describe 3 features of the group 2 metabotropic receptors

A
  • located pre synaptically
  • Gi/o coupled = NT inhibited release
  • include subtypes mGlu2 and mGlu3
25
Q

Describe 3 features of the group 3 metabotropic receptors

A
  • located pre synaptically
  • Gi/o coupled = NT inhibited release
  • include subtypes mGlu4/6/7/8
26
Q

What is meant by excitatory postsynaptic current

A

the flow of ions and current across a postsynaptic membrane

27
Q

How do excitatory postsynaptic currents increase the likelihood of an action potential firing

A

they lead to excitatory postsynaptic potentials

28
Q

Why are EPSCs slower and longer in NMDA and kainate receptors than AMPA receptors

A

AMPA receptors are the primary mediators of excitatory neurotransmission

29
Q

What is excitotoxicity

A

excessive excitatory stimulation can lead to neuronal damage and death

30
Q

How does excitotoxicity lead to neuronal damage

A
  • damage to vesicular glutamate transporters = build up of glutamate in presynaptic neuron
  • EAATs reverse their function and pump glutamate into the synaptic cleft (it is released without AP firing)
  • postsynaptic AMPA NMDA receptors are activated = influx of Ca2+ into postsynaptic neuron in an uncontrolled manner
31
Q

What are the consequences of excessive Ca2+

A
  • mitochondrial damage
  • oxidative stress
  • apoptosis
32
Q

Name a disease excitotoxicity can lead to

A

Alzheimer’s

33
Q

What is Alzheimer’s disease and name a drug used in the treatment of alzheimer’s.

A

Neuronal cell death in the hippocampus

Memantine - an NMDA receptor antagonist - blocks NMDA receptor ion channel which decreases glutamate neurotoxicity

34
Q

What is meant by long term potentiation

A

persistent strengthening of a synapse based upon repeated patterns of activity

35
Q

Describe initial phase long-term potentiation mechanism of action

A
  • glutamate activates AMPA receptors - Na+ influx into postsynaptic neuron = depolarisation
  • NMDA receptors open due to depolarisation which removes the Mg2+ ion from blocking voltage gated ion channel
  • Ca2+ ions enter - activates postsynaptic protein kinases (CaMKII and PKC)
  • these lead to insertion of new AMPA receptors at postsynaptic membrane = increase sensitivity to glutamate = increased ion channel conductance

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