Principles of GABA-ergic Transmission Flashcards

1
Q

What are the two main inhibitory amino acid neurotransmitters?

A

GABA

Glycine

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2
Q

What are the main excitatory amino acid neurotransmitters?

A

Glutamate

Aspartate

(L-homocysteine – sulphur containing)

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3
Q

What type of amino acids are the inhibitory neurotransmitters?

A

Neutral

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4
Q

What type of amino acids are the excitatory neurotransmitters?

A

Acidic

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5
Q

Why is GABA called GABA?

A

Gamma amino butyric acid

This is because the amino group is on the gamma carbon of GABA

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6
Q

Describe the distribution of GABA neurones.

A

Cerebral cortex

Cerebellum

Hippocampus

Corpus striatum

Hypothalamus

Dorsal horn of spinal cord

Relatively little in the PNS

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7
Q

Describe the morphology of GABA neurones.

A

They are generally short inhibitory interneurons

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8
Q

Where do you find longer GABA tracts?

A

Striato-nigral

Cerebellar

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9
Q

What is the main action of GABA neurones?

A

Widespread inhibitory action in the CNS

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10
Q

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

A

Emotional control

Motor control

Extrapyramidal activity

Endocrine function

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11
Q

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

A

Glutamic acid (glutamate)

Glutamic acid decarboxylase (GAD)

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12
Q

Where is this enzyme (GAD) found?

A

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

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13
Q

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

A

Alpha-oxoglutarate

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14
Q

How is GABA broken down?

A

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

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15
Q

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

A
GABA-A = type 1 – ionotropic  
GABA-B = type 2 – metabotropic- (g protein)
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16
Q

How is GABA inactivated?

A

By reuptake

17
Q

What are the GABA reuptake mechanisms dependent on?

A

Sodium dependent

Energy dependent

18
Q

Where are the transport proteins for GABA found?

A

Presynaptic neurones

Glial cells

19
Q

What type of enzyme is GAD?

A

Cytoplasmic enzyme

20
Q

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

A

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

Vigabatrin (selective GABA-T inhibitor)

21
Q

Where are GABA-A receptors found?

A

Postsynaptic

22
Q

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

A

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

23
Q

Name two agonists of GABA-A.

A

GABA

Muscimol

24
Q

Name two antagonist of GABA-A

A

Bicuculline (competitive antagonist)

Picrotoxin (non-competitive antagonist)

25
Q

What effect do the GABA antagonists have?

A

They are convulsants

They are used experimentally but not therapeutically

26
Q

Where are GABA-B receptors located?

A

Presynaptic

27
Q

What is the effect of GABA-B?

A

It is the negative feedback receptor for GABA release

similar to the effect of alpha-2 receptors on noradrenaline release

28
Q

What are the two different terms used to describe GABA-B receptors that regulate GABA release and other neurotransmitter release (e.g. dopamine)?

A

Autoreceptors – when they regulate GABA release

Heteroreceptors – when they regulate the release of other neurotransmitters

29
Q

Describe the mechanism of action of GABA-B receptors.

A

G protein linked receptor

Causes a decrease in calcium conductance

Reduction in neurotransmitter release

Stimulation of GABA-B also causes a reduction in cAMP

30
Q

Name two agonists of GABA-B receptors.

A

Baclofen

GABA

31
Q

Name an antagonist of GABA-B receptors.

A

Saclofen (competitive antagonist)

32
Q

What can GABA-B receptor agonists be used for?

A

Muscle relaxant and spasmolytic

Mechanism – reduced GABA release in the spinal cord and reduced activation of alpha motor neurone output causes relaxation of skeletal muscles

This reduces spasticity

33
Q

Describe how G-protein coupling works. (GABA-B)

A

GABA binds to the GABA receptor and changes its conformation so that it can bind the alpha subunit of the G protein

The alpha subunit normally has GDP bound to it, when it binds to the receptor it exchanges GDP for GTP

The alpha-GTP subunit is active at the target

The alpha subunit breaks down GTP to GDP, which then inactivates it