Glutamate And GABA

Question 1

Is Glutamate an excitatory or inhibitor NT?

Answer 1

Excitatory

Question 2

Where is glutamate most widely distributed in the body?

Answer 2

70% in the CNS

Question 3

How is glutamate made in the neurone?

Answer 3

Glutamine is converted to glutamate by Glutaminase. Then it is degraded to alpha-oxoglutarate by transaminase

Question 4

How it glutamate formed in Glia cells?

Answer 4

Alpha-oxoglutarate is converted to glutamate by GABA transaminase. It is degraded to Glutamine by Glutamine synthase

Question 5

What are the three different types of vesicular-glutamate transporter pumps?

Answer 5

VGluT1
VGluT2
VGluT3

Question 6

What is transported out of the vesicle in order for glutamate to be transported into the vesicle?

Answer 6

2 x H+ ions

Question 7

How is the inside of the storage vesicle kept at a low pH?

Answer 7

Another proton pump/ATPase which pumps H+ into the cell against it’s concentration gradient. Needs ATP

Question 8

Which channels opens after depolarisation occurs to release the glutamate form the vesicle?

Answer 8

Voltage gated Ca channels

Question 9

What are the three ionotropic glutamate receptors? (Ion channels activated by glutamate)

Answer 9

NMDA cation channel - Na, K, Ca
AMPA cation channel - Na, K, (some Ca)
Kainate cation channel - N, K

Question 10

What are the three metabotropic receptors what glutamate acts upon? (G-protein coupled receptors, Class C)

Answer 10

Group 1 - mGluR1 + mGluR5 couple to Gq and G11 G-proteins
Group 2 - mGluR2 + mGluR3 couple to Go and Gi G-proteins
Groups 3 - mGluR4 + mGluR6-8 couple to Go and Gi G-proteins

Question 11

What is the structure of Inotropic glutamate receptor?

Answer 11

Heterotetromer
Bind to glutamate at the N terminus
3 alpha helices and inverted P loop

Question 12

What is the structure of the G-coupled glutamate receptors?

Answer 12

7 transmembrane domains
Binding site outside on the N terminus
Coupling region on the third intracellular loop
Activate second messenger system

Question 13

How is glutamate recycled?

Answer 13

Either taken up into the glial cells where it is converted to glutamine or repackaged into vesicles in the neurone

Question 14

How is glutamate removed from the synaptic cleft?

Answer 14

EAAT

Question 15

Which drugs work on the NMDA glutamate receptor?

Answer 15

Ketamine - channel blocker

Meantime - competitive antagonist

Question 16

Which drug works on the AMPA glutamate receptor?

Answer 16

Perampanel - noncompetitive antagonist

Question 17

Which recreational drugs involved the glutamate receptors?

Answer 17

Ketamine

PCP (phencyclidine)

Question 18

Which diseases can be therapeutically controlled by manipulation of the glutamate receptors?

Answer 18

Epilepsy
Alzheimer’s
Anaesthetic

Question 19

Is GABA an inhibitory or excitatory neurotransmitter?

Answer 19

Inhibitory

Question 20

How is GABA made?

Answer 20

From glutamate via the glutamic acid decarboxylase enzyme (GAD)

Question 21

What is the name of the transporter which concentrates GABA into it’s storage vesicle?

Answer 21

Vesicular GABA transporter

Question 22

What is needed for release of GABA from the vesicles?

Answer 22

Ca influx

Question 23

Which ionotropic receptors are activated by GABA?

Answer 23

GABAa receptor - anion Cl-

Question 24

Which metabotropic receptors do GABA work on?

Answer 24

GABAb receptors coupled to Gi and Go proteins

Question 25

What is the structure of the ionotropic receptor GABAa?

Answer 25

Heteropentomer - 5 subunits 2 binding sites for GABA Cl- pore in the middle so when GABA binds, Cl- ions can flow through in the cell

Question 26

What is the structure of the metabotropic GABAb receptor?

Answer 26

7 transmembrane units GABA binds to N terminus Third loop modifies cell’s biochemistry

Question 27

How is GABA removed from the synaptic cleft?

Answer 27

Via the reuptake protein

Question 28

Which reuptake proteins are present on neurones?

Answer 28

GAT1

Question 29

Which reuptake proteins are on astrocytes, in particular glial cells?

Answer 29

GAT3

Question 30

How is GABA degraded?

Answer 30

It is broken down to Succinic semialdehyde via the GABA transaminase

Question 31

Which drugs act via the GABAa receptor?

Answer 31

Benzodiazepines, alcohol and some general anaesthetics (propofol) are all positive allosteric modulators

Question 32

Which drugs work via the GABAb receptors?

Answer 32

Baclofen (agonist) | Saclofen (competitive antagonist)

Question 33

Which two drugs used in Epilepsy work via the GABA system and how?

Answer 33

Tiagabine - blocks GAT | Vigabatrine - blocks GABA-t

Question 34

Which recreational drugs work via the GABA system?

Answer 34

Barbiturates | Nitrous oxide