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Flashcards in Principles of GABA-ergic Transmission Deck (36)
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1

What are the two main inhibitory amino acid neurotransmitters?

GABA
Glycine

2

What are the main excitatory amino acid neurotransmitters?

Glutamate
Aspartate
(L-homocysteine – sulphur containing)

3

What type of amino acids are the inhibitory neurotransmitters?

Neutral

4

What type of amino acids are the excitatory neurotransmitters?

Acidic

5

Why is GABA called GABA?

Gamma amino butyric acid
This is because the amino group is on the gamma carbon of GABA

6

Describe the distribution of GABA neurones.

Cerebral cortex
Cerebellum
Hippocampus
Corpus striatum
Hypothalamus
Dorsal horn of spinal cord
Relatively little in the PNS

7

Describe the morphology of GABA neurones.

They are generally short inhibitory interneurons

8

Where do you find longer GABA tracts?

Striato-nigral
Cerebellar

9

What is the main action of GABA neurones?

Widespread inhibitory action in the CNS

10

What are the main functions of GABA neurones in terms of CNS activity?

Emotional control
Motor control
Extrapyramidal activity
Endocrine function

11

What is the precursor for GABA and what enzyme converts it to GABA?

Glutamic acid
Glutamic acid decarboxylase (GAD)

12

Where is this enzyme found?

This enzyme is exclusive to GABA nerve terminals – it is a marker for GABA neurones

13

What product of the Krebs’ cycle gives rise to glutamate?

Alpha-oxoglutarate

14

How is GABA broken down?

Initially by GABA-T (GABA transaminase) to succinic semialdehyde
Succinic semialdehyde is broken down by succinic semialdehyde dehydrogenase (SSDH) to succinate
Succinate then enters the Krebs’ cycle

15

Describe the release of GABA from GABAergic nerve terminals.

Calcium-mediated exocytosis

16

What are the two main GABA receptors and why type of receptorsare they?

GABA-A = type 1 – ionotropic
GABA-B = type 2 – metabotropic

17

How is GABA inactivated?

By reuptake

18

What are the uptake mechanisms dependent on?

Sodium dependent
Energy dependent

19

Where are the transport proteins for GABA found?

Presynaptic neurones
Glial cells

20

What type of enzymes are the enzymes that break down GABA?

Mitochondrial enzymes

21

What type of enzyme is GAD?

Cytoplasmic enzyme

22

Name two drugs that are used as anti-convulsants that decrease the metabolism of GABA.

Sodium valproate (acts on GABA-T and SSDH (but more so on SSDH))
Vigabatrin (selective GABA-T inhibitor)

23

Where are GABA-A receptors found?

Postsynaptic

24

Describe the structure of GABA-A receptors.

They are ionotropic receptors (type 1)
They have a pentameric structure consisting of the following subunits:
 2 x alpha
 2 x beta
 1 x gamma

25

What is the mechanism of action of GABA-A receptors?

GABA binding causes opening of the chloride channel leading to chloride influx
This causes hyperpolarisation of the postsynaptic neurone (inhibitory post-synaptic potential)
This causes inhibition of firing

26

Name two agonists of GABA-A.

GABA
Muscimol

27

Name two antagonist of GABA-A

Bicuculline (competitive antagonist)
Picrotoxin (non-competitive antagonist)

28

What effect do the antagonists have?

They are convulsants
They are used experimentally but not therapeutically

29

Where are GABA-B receptors located?

Presynaptic

30

What is the effect of GABA-B?

It is the negative feedback receptor for GABA release (similar to the effect of alpha-2 receptors on noradrenaline release)