Glutamate (FS - Week 2)

Question 1

What type of neurotransmitter is glutamate

Answer 1

excitatory

Question 2

Where is glutamate synthesised?

Answer 2

in the nerve terminals

Question 3

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

Answer 3

Glutaminase

Question 4

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

Answer 4

VGLUT

Question 5

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

Answer 5

EAAT

Question 6

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

Answer 6

glutamine synthase

Question 7

What is the name of the transporter on Glial cells?

Answer 7

SN1

Question 8

What is the name of transporters on neurons?

Answer 8

SAT2

Question 9

Name the 3 ionotropic glutamate receptors

Answer 9

• AMPA receptors
• NMDA receptors
• Kainate receptors

Question 10

Name the 3 metabotropic glutamate receptors

Answer 10

• Group I
• Group II
• Group III

Question 11

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

Answer 11

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

Question 12

How many subtypes of AMPA receptors are there?

Answer 12

4

• GluA1
• GluA2
• GluA3
• GluA4

Question 13

How many binding sites are there on the AMPA receptor?

Answer 13

4

Question 14

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

Answer 14

2

Question 15

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

Answer 15

GluA2

prevents excitotoxicity

Question 16

How many subunit types are there of the NMDA receptor

Answer 16

• GluN1
• GluN2
• GluN3

Question 17

What is the typical composition of an NMDA receptor

Answer 17

2 GluN1 and 2 GluN2/3

Question 18

What subtype is inhibitory in the NMDA receptor function

Answer 18

GluN3

Question 19

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

Answer 19

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

Question 20

What subunits does glutamate bind to on the NMDA receptor

Answer 20

GluN2

Question 21

How many subtypes of the Kainate receptor are there?

Answer 21

5

- GluK1 > 5

Question 22

How many subtypes of metabotropic glutamate receptors are there?

Answer 22

8

mGlu1-8

Question 23

Describe 3 features of the group 1 metabotropic receptors

Answer 23

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

Question 24

Describe 3 features of the group 2 metabotropic receptors

Answer 24

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

Question 25

Describe 3 features of the group 3 metabotropic receptors

Answer 25

- located pre synaptically - Gi/o coupled = NT inhibited release - include subtypes mGlu4/6/7/8

Question 26

What is meant by excitatory postsynaptic current

Answer 26

the flow of ions and current across a postsynaptic membrane

Question 27

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

Answer 27

they lead to excitatory postsynaptic potentials

Question 28

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

Answer 28

AMPA receptors are the primary mediators of excitatory neurotransmission

Question 29

What is excitotoxicity

Answer 29

excessive excitatory stimulation can lead to neuronal damage and death

Question 30

How does excitotoxicity lead to neuronal damage

Answer 30

- 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

Question 31

What are the consequences of excessive Ca2+

Answer 31

- mitochondrial damage - oxidative stress - apoptosis

Question 32

Name a disease excitotoxicity can lead to

Answer 32

Alzheimer's

Question 33

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

Answer 33

Neuronal cell death in the hippocampus | Memantine - an NMDA receptor antagonist - blocks NMDA receptor ion channel which decreases glutamate neurotoxicity

Question 34

What is meant by long term potentiation

Answer 34

persistent strengthening of a synapse based upon repeated patterns of activity

Question 35

Describe initial phase long-term potentiation mechanism of action

Answer 35

- 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