GABA

Question 1

What type of neurotransmitter is GABA?

Answer 1

Traditional small molecule

Main inhibitory neurotransmitter

Question 2

How is GABA synthesised?

Answer 2

From glutamate, by glutamate decarboxylase (GAD), in nerve terminals
GAD67 throughout body
GAD65 in nerve terminals

Question 3

What transporters move GABA into cells?

Answer 3

GAT1 and GAT3

Question 4

What transporters move GABA into vesicles?

Answer 4

VGAT

Question 5

Describe the structure of the GABAa receptor

Answer 5

Pentameric
4 transmembrane domains
Extracellular C and N terminus
N terminus has cys-cys loop with disulfide bond

Question 6

Describe the subunit composition of the GABAa receptor

Answer 6

19 possible subunits (alpha, beta, gamma, delta, phi)

Almost always 2 alpha, 2 beta and a gamma or delta

Question 7

What happens when the GABAa receptor is activated?

Answer 7

Chloride ion influx into the postsynaptic cell leading to hyperpolarisation
Known as an IPSP

Question 8

Where does GABA bind on the GABAa receptor?

Answer 8

Interface between alpha and beta subunits

Question 9

Give an example of a GABAa receptor subunit that is only found in one region of the brain

Answer 9

Alpha6 is only present in the cerebellum

Question 10

Name 4 things that are positive allosteric modulators of the GABAa receptor

Answer 10

Alcohol
Benzos
Barbiturates
Neurosteroids

Question 11

Describe the structure of the GABAb receptor

Answer 11

Obligate dimer - 2 interacting GPCRs
7 transmembrane domains
Extracellular N terminus, intracellular c terminus 
GABAb-R1 binds GABA
GABAb-R2 interacts with the G proteins

Question 12

What type of G protein is the GABAb receptor linked to?

Answer 12

Gi/o

Question 13

What happens when the GABAb receptor is activated?

Answer 13

Activation of GIRK potassium channels; postsynaptic potassium efflux and hyperpolarisation
Inactivation of presynaptic VOCCs
Inhibition of adenylyl cyclase and cAMP signalling

Question 14

Where are GABAa receptors and GABAb receptors found?

Answer 14

GABAa is postsynaptic only

GABAb is postsynaptic and presynaptic

Question 15

Name two agonists of the GABAb receptor

Answer 15

GABA

Baclofen

Question 16

Why don’t GABA receptors occur on dendritic spines?

Answer 16

They are not permeable to calcium therefore are not involved in any biochemical changes, only voltage changes

Question 17

Why are GABA-mediated IPSPs biphasic?

Answer 17

Initial IPSP caused by GABAa receptors

Slower prolonged IPSP caused by slower acting GABAb receptors

Question 18

What is wiring transmission vs volume transmission?

Answer 18

Wiring transmission = between compact, well define structures, resulting in localised responses e.g. at a synapse
Volume transmission = covers large areas e.g. neuromodulators that diffuse over a wide area

Question 19

How is the GABAc receptor distinguishable from the GABAa receptor?

Answer 19

Made from rho subunits only

Insensitive to classic GABAa antagonists such as bicuculline and GABAzine

Question 20

What is an orthosteric ligand?

Answer 20

Ligand that binds to the main binding site

Question 21

Name two agonists of the GABAa receptor

Answer 21

GABA

Muscimol

Question 22

Name two competitive antagonists of the GABAa receptor

Answer 22

Bicuculline

GABAzine

Question 23

Name a non competitive antagonist of the GABAa receptor

Answer 23

Picrotoxin (pore blocker)

Question 24

Where do benzos bind to the GABAa receptor?

Answer 24

Interface between alpha and gamma subunit

Question 25

Which type of GABAa receptors will benzos not work on?

Answer 25

Those containing an alpha4 or alpha6 subunit

Question 26

Name 3 uses of benzos

Answer 26

Anticonvulsant
Promote sleep
Reduce anxiety

Question 27

Name a competitive antagonist of the BDZ binding site and what it could be used for

Answer 27

Flumanezil - treat overdoses