OCB03-2008 GABA

Question 1

What does GABA stand for?

Answer 1

γ-amino butyric acid

Question 2

What is the role of GABA in the central nervous system?

Answer 2

Major inhibitory neurotransmitter (~50% of pathways) in CNS

Question 3

What two defects is GABA implicated in?

Answer 3

Epilepsy (loss of inhibition)

Huntington’s disease - neurodegeneration of GABAergic spiny neurons

Question 4

How is GABA formed?

Answer 4

From glutamate by glutamic acid decarboxylase (GAD) found only in GABA synthesising neurons

Question 5

Briefly describe release and reuptake processes of GABA.

Answer 5

(Similar to glutamate)
Stored in vesicles and exocytosed due to calcium influx

Diffuses then is taken up into astrocytes and neurons which terminates action

Question 6

What is the function of GABA transaminase?

Answer 6

GABA –> succinic semi aldehyde

Question 7

What enzyme catalyses the reaction of GABA –> succinic semi aldehyde?

Answer 7

GABA transaminase

Question 8

What is the function of glutamic acid decarboxylase?

Answer 8

Glutamate –> GABA

Question 9

What are the two types of GABA receptor?

Answer 9

Ionotropic = GABA A receptors

Metabotropic = GABA B receptors

Question 10

Where are GABA A receptors found?

Answer 10

Postsynaptic neurons

Question 11

What type of receptor does benzodiazepine act on?

Answer 11

GABA A receptors

Question 12

Where are GABA B receptors found?

Answer 12

Pre and postsynaptically

Question 13

Describe a GABA A receptor. (5)

Answer 13

Ionotropic

Postsynaptic

Mediates fast inhibition

5 subunits

Selective for anions

Question 14

What are the five subunits of a GABA A receptor?

Answer 14

2 x α

2 x β

1 x γ

Question 15

What happens when GABA binds to a GABA A receptor?

Answer 15

Conformational change = pore opens

Anions/Cl- enters cell down concentration gradient

Hyperpolarisation or clamping of voltage near resting potential

Question 16

What can blockages of GABA A receptors result in?

Answer 16

Hyperactivity of neurons = convulsions

Question 17

What drugs (4) can enhance the opening of GABA A receptors and what is their general mode of action?

Answer 17

Ethanol

Benzodiazepine

Barbituates

General anaesthetics

Allosteric mode of action

Question 18

What allosteric site do benzodiazepines bind to on GABA A receptors?

Answer 18

Where α and γ subunits interact

Question 19

What effect do benzodiazepines have on GABA A receptors?

Answer 19

Increase probability of channel opening with no effect on channel properties

Question 20

What type of drug is midazolam and what does it do/used for?

Answer 20

Benzodiazepine

Short-acting, used for sedation or anti-anxiety drug during minor invasive procedures

Question 21

What do fluorine volatile general anaesthetics do?

Answer 21

Promote GABA A channel activation/opening

Question 22

What type of drug is enflurane?

Answer 22

Fluorine volatile general anaesthetic

Question 23

Describe a GABA B receptor. (3)

Answer 23

Metabotropic/7TMGPCR

Coupled to Gi

Pre and postsynaptic

Question 24

What are the general functions of a GABA B receptor?

Answer 24

α-GTP inhibits adenylyl cyclase

βγ subunit coupled to ion channels

Question 25

What happens when a presynaptic GABA B receptor is activated?

Answer 25

βγ subunit inhibits voltage-gated Ca channels to decrease NT release

Question 26

What happens when a postsynaptic GABA B receptor is activated?

Answer 26

βγ subunit increases opening of K channels = IPSP

Reduced firing of AP

Question 27

What is baclofen?

Answer 27

GABA B agonist used to treat muscle spasticity

Question 28

What is the general effect of activating a GABA B receptor?

Answer 28

Long-lasting inhibition