Glutamate

Question 1

What are the ionotropic glutamate receptors?

Answer 1

NMDA, AMPA, Kainate

Question 2

What ions are NMDA receptors permeable to?

Answer 2

Sodium, Potassium, Calcium

Question 3

How many subunits do all the ionotropic glutamate receptors have?

Answer 3

4 (Tetramers)

Question 4

What is the subunit composition of an NMDA receptor?

Answer 4

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

Question 5

Agonists of the NMDA receptor

Answer 5

NMDA, Glutamate, Aspartate

Question 6

Modulators of the NMDA receptor

Answer 6

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

Question 7

Where can NMDA receptors be located?

Answer 7

Presynaptically
Postsynaptically
On glial cells

Question 8

What responses is the NMDA receptor involved in?

Answer 8

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

Question 9

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

Answer 9

1 gene

8 different splice forms

Question 10

How many genes are there for the GluN2 subunit?

Answer 10

4 genes

Question 11

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

Answer 11

On the GluN1 subunit

Can bind glycine or D-serine

Question 12

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

Answer 12

On the GluN2 subunit

Question 13

What are the 3 requirements for NMDA receptor activation?

Answer 13

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

Question 14

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

Answer 14

Glial cells - this is how glial cells modulate neurotransmission

Question 15

Examples of competitive antagonists of the NMDA receptor

Answer 15

AP5

CPPene

Question 16

What ions are AMPA receptors permeable to?

Answer 16

Sodium and potassium, and SOMETIMES calcium

Question 17

Where can AMPA receptors be located?

Answer 17

Postsynaptically

On glial cells

Question 18

What are the functions of the AMPA receptor?

Answer 18

Mediates the majority of fast excitatory neurotransmission (Fast EPSPs)

Question 19

What is the subunit composition of an AMPA receptor?

Answer 19

Made of up any 4 from GluA1-4 subunits

Always has GluA2 subunit

Question 20

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

Answer 20

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

Question 21

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

Answer 21

Competitive = NBQX

Non competitive = Telampanel

Question 22

Name two positive allosteric modulators of the AMPA receptor

Answer 22

Cyclothiazide

Ampakines

Question 23

What ions are Kainate receptors permeable to?

Answer 23

Sodium and potassium

Question 24

What is the subunit composition of a Kainate receptor?

Answer 24

Made up of any 4 from GluK1-5 subunits

Question 25

Where can Kainate receptors be located?

Answer 25

Presynaptically Postsynaptically (Limited distribution)

Question 26

What are the functions of the Kainate receptor?

Answer 26

Fast EPSPs | Presynaptic inhibition

Question 27

What is demoic acid?

Answer 27

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

Question 28

Name two competitive antagonists of the kainate receptor

Answer 28

CNQX, ACET

Question 29

What are the metabotropic glutamate receptors?

Answer 29

mGlu1-8

Question 30

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

Answer 30

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

Question 31

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

Answer 31

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

Question 32

Where are Group 1 mGlu receptors located?

Answer 32

Postsyanptically | On glial cells

Question 33

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

Answer 33

Presynaptically

Question 34

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

Answer 34

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

Question 35

What is the function of Group 1 mGlu receptors?

Answer 35

Slow excitatory neurotransmission | Increases postsynaptic intracellular calcium

Question 36

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

Answer 36

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

Question 37

What charge does glutamate have?

Answer 37

Anion (negative charge)

Question 38

Where does glutamate come from?

Answer 38

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

Question 39

Which transporters move glutamate into neurons?

Answer 39

EAAT1-5 (mostly EAAT2) | Excitatory amino acid transporters

Question 40

Which transporters move glutamate into vesicles?

Answer 40

VGLUT1-3

Question 41

How is the action of glutamate terminated?

Answer 41

Diffusion and EAAT-mediated uptake

Question 42

What are the features of a tripartite synapse?

Answer 42

Presynaptic neuron Postsynaptic neuron Astrocyte (or other glial cell)

Question 43

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

Answer 43

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

Question 44

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

Answer 44

Ketamine | Memantine