GABA

Question 1

GABA is the principle … transmitter in the CNS

Answer 1

Inhibitory

Question 2

GABA synthesis

Answer 2

Produced via enzymatic synthesis from glucose via Kreb’s cycle.
In nerve terminal

Question 3

GABA storage

Answer 3

Taken up by vesicular GABA transporters and stored until calcium dependent exocytosis occurs

Question 4

Reuptake of GABA

Answer 4

Reuptake by GABA Transporters (GAT)
The rest is converted into succinic semialdehyde by GABA transaminase
Or can be taken up by vesicles in glial cells and converted there.

Question 5

Role of GABA neurons

Answer 5

Cerebellum, basal ganglia, hippocampus, hypothalamus, cortex.
Prominent roles in local interneurons.
Also found in relay and projection neurons

Question 6

Local interneurons

Answer 6

Have short projections and regulate the interactions of the local circuit.
Connections are limited to other neurons in the local area.

Question 7

GABA A

Answer 7

• Ligand gated ion channels
• Permeable to Cl- ions
• Hyperpolarises membrane
• Primarily postsynaptic
• Mediate fast inhibition

Question 8

GABA B

Answer 8

• G-protein-coupled receptors (GPCR)
• Coupled to Ca2+ and K+ ion channels
• Pre and postsynaptic
• Mediate slow inhibition (seconds-minutes)
• Also inhibit transmitter release

Question 9

GABA A action

Answer 9

GABA opens channel
Low intracellular Cl- causes an inward current of Cl
This causes an inhibitory postsynaptic potential (IPSP), which makes the neuron less likely to fire

Question 10

GABA A structure

Answer 10

Pentameric combinations of subunits arranged to make a channel
Main receptor in our brain has two α, two β and one γ-subunit
GABA binds between α and β, so two molecules are needed for activation

Question 11

Subunits in GABA A

Answer 11

Each subunit has 4 trans-membrane segments
TM2 is the pore forming segment which faces into the channel and contributes to the ion selectivity

Question 12

Pharmacology of GABA A

Answer 12

Benzodiazepine binds and potentiates GABA increasing frequency of channel opening
Barbiturates/anaesthetics bind and potentiate GABA, prolonging channel opening
Channel blocking sites block Cl- permeability

Question 13

GABA B receptors are _ coupled

Answer 13

Gαi/o

Question 14

GABA B are GCPRs with _ transmembrane segments

Answer 14

7

Question 15

GABA B receptors couple to and open _ channels in _ synaptic neurons

Answer 15

K+, post
Allows K+ to leave cell
Hyperpolarisation

Question 16

Gβγ subunit closes _-channels in _synaptic terminals

Answer 16

Ca2+, pre

Question 17

Formation of GABA B

Answer 17

R1 in the endoplasmic reticulum binds GABA, inducing change in proteins, inducing change in cytoplasm.
Dimerises with R2 (where G protein couples) in the cell membrane to form functional GABA_B R

Question 18

GABA B receptors are obligatory _

Answer 18

Heterodimers

Question 19

Presynaptic GABA _ can mediate the effect of post synaptic GABA _

Answer 19

B, A

Question 20

GABA B agonists are used to treat …

Answer 20

spasticity by activating postsynaptic GABABR on motor neurones

Question 21

GABA B antagonists are used to treat

Answer 21

epilepsy by blocking postsynaptic GABA B R on GABA neurones to prevent the reduction of GABA release and to increase synaptic inhibition.