Glutamate

Question 1

The main _ transmitter in the CNS

Answer 1

Excitatory

Question 2

Glutamate is synthesised from…

Answer 2

Glutamine

Question 3

Reuptake of glutamate is done by …

Answer 3

Excitatory Amino Acid Transporters (EAAT)

Question 4

Synthesis of Glutamate

Answer 4

Glutamine transported into pre-synaptic neuron
Converted into glutamate
Stored in vesicles

Question 5

Use and reuptake of Glutamate

Answer 5

During depolarization, vesicles bind to cell wall and release glutamate into synapse
Taken up again by EAAT
Stored in pre-synaptic neuron or in glial cell

Question 6

Glutamine is transported into pre-synaptic neuron by …

Answer 6

Glutamine transporter

Question 7

Glutamine is converted to glutamate by…

Answer 7

Glutaminase

Question 8

What happens to synaptic glutamate?

Answer 8

Can be taken up by EAAT and stored back in the pre-synaptic neuron.
Can be taken up into the glial cell and stored as glutamine

Question 9

Excitotoxicity

Answer 9

When there is so much excitation of glutamate receptors that it causes cell death.

Question 10

Glutamate acts via _tropic and _tropic receptors

Answer 10

Ionotropic: NMDA, AMPA and KA
Metabotropic: Group I, Group II, Group III

Question 11

NMDA receptor names

Answer 11

GluN1
GluN2A
etc

Question 12

AMPA receptor names

Answer 12

GluA1
GluA2
etc

Question 13

KA receptor names

Answer 13

GluK1
GluK2
etc

Question 14

Group 1 receptors

Answer 14

mGluR1 and mGluR5
Increase calcium and IP3

Question 15

Group 2 receptors

Answer 15

mGluR2 and mGluR3
Decrease cAMP

Question 16

Group 3 Receptors

Answer 16

mGluR4, mGluR6, mGluR7, mGluR8
Decrease cAMP

Question 17

Why can glutamate bind so many receptors?

Answer 17

Because it doesn’t have a rigid shape

Question 18

Shape of glutamate

Answer 18

Nine ‘rotamers’ are possible
Contains different constituents that can rotate along two different axes about the alpha beta and beta gamma bonds

Question 19

Structure of ionotropic glutamate receptors

Answer 19

Tetrameric ligand gated ion channels
Subunits have 4 membrane sections
Extracellular loop between 3 and 4 forms part of the binding principle
P-elements face inward and form the channel

Question 20

Subunits of ionotropic glutamate receptors

Answer 20

1, 3 and 4 are trans-membrane segments
2 does not span the membrane (p-element)
Subunit composition can be heteromeric or homomeric

Question 21

NDMA will never be…

Answer 21

homomeric

Question 22

AMPAr receptor

Answer 22

Ligand gated Na+ channel
Permeable to Na+ in and K+ out
Ca2+ permeable if there is no GluA2 subunit
Fast excitatory transmission

Question 23

Agonists of AMPAr receptors

Answer 23

Glutamate
AMPA
KA

Question 24

Antagonists of AMPAr receptors

Answer 24

NBQX (competitive
GYKI 53655 (non-competitive)

Question 25

NMDA receptor

Answer 25

Dual gated Na+/Ca2+ channel Na+ out, K+ out, Ca2+ in Voltage and ligand gated, depolarisation required to relieve Mg block requires glycine or serine as co-agonist Much slower time course than AMPA

Question 26

Structure of NMDA receptor

Answer 26

1 GluN1 subunit and 3 GluN2A-D subunits

Question 27

Glycine _ NMDA receptor mediated responses

Answer 27

potentiates

Question 28

Competitive NMDA receptor antagonists

Answer 28

AP5 and CPP

Question 29

NMDA receptor ion channel blockers

Answer 29

Ketamine (high affinity) Memantine (low affinity) PCP (dissociative anaesthetic)

Question 30

mGluRs

Answer 30

GCPRs 7 transmembrane regions Slow neuromodulatory role Connected to different second messenger systems

Question 31

mGluRs and Ca2+

Answer 31

Channels normally let Ca2+ in Glutamate activates Ca channel closure Controls transmitter release Activation of intracellular enzyme releases Ca2+ from intracellular stores

Question 32

Activation of intracellular enzyme releases Ca2+ from intracellular stores

Answer 32

IP3 Initiation of second messenger cascade causes further enzyme activation. Opening/closing of ion channels Modulation of postsynaptic excitability Important for excitotoxicity and neurodegeneration

Question 33

mGluRs and K+

Answer 33

Channels normally let K+ out Glutamate activates mGluR Leads to K-channel closure Leads to slow depolarization

Question 34

mGluR1 and mGluR5

Answer 34

postsynaptic produce slow depolarisation release Ca2+ from intracellular stores

Question 35

mGluR2, 3, 4, 7 & 8

Answer 35

presynaptic usually inhibit glutamate (and other transmitters) release

Question 36

Presynaptic NMDAr _ glutamate release by _ Ca influx.

Answer 36

increase, increase

Question 37

Presynaptic mGluR _ glutamate release by _ Ca influx

Answer 37

decrease, decreasing