Lecture 10. Glutamatergic Synaptic Transmission and the Trafficking of Transmembrane Receptors

Question 1

What is the major excitatory neurotransmitter in the mammalian CNS?

Answer 1

L-Glutamate

Question 2

What are L-glutamate ligand-gated ion channels called?

Answer 2

Ionotropic GluRs (iGluR)

Question 3

What are L-glutamate G-protein coupled receptors called?

Answer 3

Metabotropic GluRs (mGluR)

Question 4

What are the three types of iGluRs?

Answer 4

NMDA receptor
AMPA receptor
Kainate receptor

Question 5

What G-protein are coupled to group I mGluRs?

Answer 5

Gαq

Question 6

What G-protein are coupled to group II mGluRs?

Answer 6

Gαi

Question 7

What G-protein are coupled to group III mGluRs?

Answer 7

Gαi

Question 8

What is the obligatory receptor of NMDA?

Answer 8

GluN1 (has to be there or else not a NMDA receptor)

Question 9

What are the three subunits of NMDA receptors?

Answer 9

GluN1
GluN2A-D
GluN3A,B

Question 10

What are the four subunits of AMPA receptors?

Answer 10

GluA1-4

Question 11

What are the five subunits of kainate receptors?

Answer 11

GluK1-5

Question 12

What are the two subtypes of mGluR group I?

Answer 12

mGlu1
mGlu5

Question 13

What are the two subtypes of mGluR group II?

Answer 13

mGlu2
mGlu3

Question 14

What are the four subtypes of mGluR group III?

Answer 14

mGlu4
mGlu6
mGlu7
mGlu8

Question 15

What effect are brought about by iGluRs?

Answer 15

Fast, excitatory

Question 16

What effect are brought about by mGluRs?

Answer 16

Slow, excitatory or inhibitory

Question 17

How does glutamate arise in the synapse?

Answer 17

Either converted from glutamine taken up by the neurone from a glial cell/astrocyte or as a product of the tricarboxylic acid cycle

Question 18

How is glutamate packed into vesicles?

Answer 18

Through the creation of a H⁺ ion gradient that supports the uptake of Glu⁻

Question 19

What uptakes glutamate, allowing glutamate supply to be recycled?

Answer 19

EAAT1-4 (excitatory amino acid transporter)

Question 20

What EAATs are located on the glial cell?

Answer 20

EAAT1-2

Question 21

What EAATs are located on the neurone?

Answer 21

EAAT3-4

Question 22

Why do glial cells possess EAAT?

Answer 22

Due to being in close proximity of the neurone (tripartite synapse)

Question 23

How many agonists must bind to the NMDA receptor to activate it?

Answer 23

2

Question 24

What ion blocks the transmembrane pore?

Answer 24

Mg²⁺

Question 25

What are the co-agonists of the NMDA receptor that bind to GluN1?

Answer 25

Glycine and D-serine (normally always present so don't think about them)

Question 26

What ion regulatory site is present on GluN2?

Answer 26

Zn²⁺

Question 27

What does rectifying mean?

Answer 27

When the flow of ions through a channel is favoured in one direction supposed to the other direction

Question 28

What can AMPA receptor subunits affect?

Answer 28

Function, can fine tune activity due to certain stimuli. Can cause post-translational modifications that can influence the function of particular circuits

Question 29

What does arginine block?

Answer 29

Ca²⁺

Question 30

What is the difference in I/V curve between Ca²⁺-permeable and Ca²⁺-impermeable AMPA receptors?

Answer 30

Ca²⁺-permeable = rectifying Ca²⁺ impermeable = linear

Question 31

What are the roles of glutamate receptors in the mammalian brain?

Answer 31

Mediate the majority of fast excitatory synaptic transmission in the CNS Vital to many basic functions – cognition, movement, central cardiovascular, thermoregulatory & respiratory control Changes in glutamatergic synaptic strength may underpin learning and memory Implicated in a host of neurodevelopmental, neurological, neurodegenerative and psychiatric conditions (eg autism, epilepsy, stroke, Alzheimer’s disease, schizophrenia) Target of drugs of abuse – Ketamine (Special K), Phencyclidine (PCP; Angel Dust)

Question 32

What are the trafficking levels into and out of synapses?

Answer 32

Very high

Question 33

Why does Mg²⁺ block NMDA receptors when the cell is hyperpolarised?

Answer 33

The ion is more strongly attracted to the receptor, ion attracted more strongly into the channel

Question 34

What are active synapses?

Answer 34

Transmits information at hyperpolarised (resting) membrane potentials through AMPA receptors

Question 35

What are silent synapses?

Answer 35

Ones that lacks AMPARs at the synapse and does NOT transmit information at hyperpolarised (resting) membrane potentials due to the Mg²⁺ block of the NMDA receptor. AMPA receptors may be stored in intracellular vesicles or at extrasynaptic sites

Question 36

Synapses containing NMDAR can recruit what?

Answer 36

AMPAR through pairing protocol (creates response at -65mV)

Question 37

How can the movement of AMPARS to the synaptic cleft be visualised?

Answer 37

Through the use of a latex bead or staining with a quantum dot

Question 38

What is long-term potentiation?

Answer 38

When high plasticity is induced in the brain thorough high frequency stimulation

Question 39

What is long-term depression?

Answer 39

When low plasticity is induced in the brain thorough low frequency stimulation, decreasing the size of the response

Question 40

What are NMDARs necessary for?

Answer 40

Long-term potentiation and spatial learning

Question 41

What are the implications of AMPAR trafficking at synapses?

Answer 41

Trafficking may underlie learning and memory, as well as a host of pathological and psychiatric conditions This clinical relevance encourages the synthesis of subtype/subunit selective GluR-based drugs and hopes for new treatments