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Neuropharmacology > Glutamate > Flashcards

Glutamate Flashcards

1
Q

What are the ionotropic glutamate receptors?

A

NMDA, AMPA, Kainate

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2
Q

What ions are NMDA receptors permeable to?

A

Sodium, Potassium, Calcium

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3
Q

How many subunits do all the ionotropic glutamate receptors have?

A

4 (Tetramers)

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4
Q

What is the subunit composition of an NMDA receptor?

A

Heterotetramer of…
Two GluN1 subunits
Two GluN2 subunits
Can also occasionally include GluN3

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5
Q

Agonists of the NMDA receptor

A

NMDA, Glutamate, Aspartate

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6
Q

Modulators of the NMDA receptor

A

Glycine, D-serine, Polyamines (such as magnesium and zinc)

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7
Q

Where can NMDA receptors be located?

A

Presynaptically
Postsynaptically
On glial cells

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8
Q

What responses is the NMDA receptor involved in?

A

Slower, longer-lasting EPSPs
Synaptic plasticity - LTP and LTD
Excitotoxicity

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9
Q

How many genes and splice forms are there for the GluN1 subunit?

A

1 gene

8 different splice forms

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10
Q

How many genes are there for the GluN2 subunit?

A

4 genes

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11
Q

Where on the NMDA receptor is the glycine binding site and what else can also bind here?

A

On the GluN1 subunit

Can bind glycine or D-serine

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12
Q

Where on the NMDA receptor is the glutamate (main) binding site?

A

On the GluN2 subunit

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13
Q

What are the 3 requirements for NMDA receptor activation?

A

Glutamate/Aspartate/NMDA binding
Co activation by glycine or D-serine
Depolarisation of neuron to remove the magnesium block

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14
Q

Where does the D-serine come from for co-activation?

A

Glial cells - this is how glial cells modulate neurotransmission

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15
Q

Examples of competitive antagonists of the NMDA receptor

A

AP5

CPPene

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16
Q

What ions are AMPA receptors permeable to?

A

Sodium and potassium, and SOMETIMES calcium

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17
Q

Where can AMPA receptors be located?

A

Postsynaptically

On glial cells

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18
Q

What are the functions of the AMPA receptor?

A

Mediates the majority of fast excitatory neurotransmission (Fast EPSPs)

19
Q

What is the subunit composition of an AMPA receptor?

A

Made of up any 4 from GluA1-4 subunits

Always has GluA2 subunit

20
Q

What determines whether or not an AMPA receptor is permeable to calcium?

A

The GluA2 subunit has a Q/R site in the amino acid chain in the pore-forming M2 region, that can be arginine or glutamine.
Glutamine = permeable
Arginine = impermeable

21
Q

Name a competitive and a non-competitive antagonist of AMPA receptors

A

Competitive = NBQX

Non competitive = Telampanel

22
Q

Name two positive allosteric modulators of the AMPA receptor

A

Cyclothiazide

Ampakines

23
Q

What ions are Kainate receptors permeable to?

A

Sodium and potassium

24
Q

What is the subunit composition of a Kainate receptor?

A

Made up of any 4 from GluK1-5 subunits

25
Q

Where can Kainate receptors be located?

A

Presynaptically
Postsynaptically
(Limited distribution)

26
Q

What are the functions of the Kainate receptor?

A

Fast EPSPs

Presynaptic inhibition

27
Q

What is demoic acid?

A

Agonist of the kainate receptor
Found in mussels
Can cause seizures, motor weakness and death

28
Q

Name two competitive antagonists of the kainate receptor

A

CNQX, ACET

29
Q

What are the metabotropic glutamate receptors?

A

mGlu1-8

30
Q

What are the groups of metabotropic glutamate receptors and which receptors does each group contain?

A

Group 1: mGlu 1, 5
Group 2: mGlu 2, 3
Group 3: mGlu 4, 6-8

31
Q

What G-protein are Group 1 mGlu receptors coupled to?

A 
Gq
Activation of PLC
PIP2 --> IP3 + DAG
DAG activates PKC
IP3 release calcium from ER
32
Q

Where are Group 1 mGlu receptors located?

A

Postsyanptically

On glial cells

33
Q

Where are Group 2 mGlu and group 3 mGlu receptors located?

A

Presynaptically

34
Q

What G-protein are Group 2 and Group 3 mGlu receptors coupled to?

A

Gi/o
Inhibition of adenylyl cyclase
Less cAMP
Less PKA activation

35
Q

What is the function of Group 1 mGlu receptors?

A

Slow excitatory neurotransmission

Increases postsynaptic intracellular calcium

36
Q

What is the function of Group 2 and Group 3 mGlu receptors?

A

Slow inhibitory neurotransmission
Open presynaptic potassium channels
Reduce presynaptic intracellular calcium
Prevent neurotransmitter release

37
Q

What charge does glutamate have?

A

Anion (negative charge)

38
Q

Where does glutamate come from?

A

Non-essential amino acid (It is synthesised endogenously, you don’t need to eat it)

39
Q

Which transporters move glutamate into neurons?

A

EAAT1-5 (mostly EAAT2)

Excitatory amino acid transporters

40
Q

Which transporters move glutamate into vesicles?

A

VGLUT1-3

41
Q

How is the action of glutamate terminated?

A

Diffusion and EAAT-mediated uptake

42
Q

What are the features of a tripartite synapse?

A

Presynaptic neuron
Postsynaptic neuron
Astrocyte (or other glial cell)

43
Q

How is glutamate in the synaptic cleft re-packaged into vesicles in the postsynaptic neuron?

A

Glutamate in the synaptic cleft transported into astrocytes by EAAT1/2
Glutamate broken down into glutamine by glutamine synthetase
Glutamine pumped back into extracellular space by Gln transporter
Glutamine uptaken by presynaptic cell byGln transporter
Glutamine converted into glutamate by glutaminase

44
Q

Name two non-competitive, low affinity antagonists of NMDA receptors

A

Ketamine

Memantine

Neuropharmacology (16 decks)

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