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PA20023 > GABA > Flashcards

GABA Flashcards

1
Q

What is GABA?

A

The principal inhibitory transmitter in the CNS - it is used in over 30% of the brain synapses.

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2
Q

What type of receptors can it activate?

A

Both ionotropic and metabotropic receptors.

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3
Q

What is the difference between ionotropic and metabotropic receptors?

A

Ionotropic act quickly whereas metabotropic act slower. Ionotropic change shape when bound to a receptor, whereas metabotropic activate a g protein that in turn activates a secondary messenger. Metabotropic receptors may cause a channel somewhere else on the membrane to be activated.

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4
Q

What is GABA formed from and via what cycle?

A

Glucose via the Krebs cycle.

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5
Q

How is GABA inactivated?

A

The reuptake by GABA transporters (GAT).

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6
Q

What roles are GABA neurones involved in?

A

Cerebellum, basal ganglia, hippocampus, hypothalamus and cortex.

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7
Q

Where is GABA principally located?

A

Local interneurones.

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8
Q

What are local interneurones?

A

Neurones with axons that spread out from the cell body, but dont go out of the area into other areas.

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9
Q

How do GABA and glutamate work together?

A

They balance excitation and inhibition and act together rather than independently. EPSP and IPSPs.

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10
Q

What is the process for GABA synthesis?

A

Glucose enters the Krebs cycle in the mitochrondria. GABA-transminase (GABA-T) converts alpha-ketaglutarate into glutamate. GAD (glutamic acid decarboxylase) converts glutamate into GABA.

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11
Q

What happens when GABA has been synthesised?

A

It is packaged into a vesicular transporter (VGAT) and released as normal.

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12
Q

How is GABA inactivated?

A

It is taken up into a type of glial cells and then metabolised by mitochondria or can pass back into the nerve terminals.

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13
Q

What are the two ways in which GABA can be reused?

A

It can be taken directly up into the vesicles by the transporter or it can be acted on by GAT which converts it into succinic semialdehyde which can then enter the krebs cycle again.

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14
Q

What are the three types of GABA receptor?

A

GABAa, GABAb, GABAc.

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15
Q

What are the features of GABAa receptors?

A

They are ligand gated ion channels that are permeable to Cl- ions. They are primarily postsynaptic and mediate fast inhibition.

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16
Q

What are the features of GABAb receptors?

A

They are G-protein coupled receptors that are coupled to Ca2+ and K+ ion channels. They are pre and post-synaptic and mediate slow inhibition. THey can also inhibit transmitter release.

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17
Q

What are the features of GABAc receptors?

A

They are ligand gated Cl- channels that are postsynaptic and mainly located in the retina. They mediate fast inhibition. They are not widely distributed in the brain.

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18
Q

What happens when GABA binds to a GABAa receptor?

A

As there is low intracellular Cl-, Cl- enters the cell and hyperpolarizes the membrane and there is an inhibitory postsynaptic potential.

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19
Q

How many subunits are in the GABAa receptor?

A

5 - they are pentameric.

20
Q

How many segments are in the GABAa receptor subunits and how do they span the membrane?

A

There are 4 transmembrane segments.

21
Q

What is the most common combination of subunits in the GABAa receptor?

A

Two alpha, two beta and one gamma.

22
Q

How many molecules of GABA are required to activate the GABAa receptor?

A

2 - they bind between the alpha and beta subunits.

23
Q

What is an isoform?

A

Functionally similar proteins that have a similar, but not identical, amino acid sequence.

24
Q

What does changing the conformation of the GABAa receptor do?

A

It can change the probability of the channel opening, the Cl- permeability, the duration of the channel opening.

25
Q

What is significant about the different binding sites of the GABAa receptors?

A

There are lots of sites that can be modified, meaning different drugs can be developed for target receptors.

26
Q

What are the agonists of the GABA binding site?

A

GABA, muscimol.

27
Q

What are the antagonists of the GABA binding site?

A

Bicuculline, gabazine.

28
Q

Where is the barbiturate/anaesthetic binding site located in the GABAa receptor?

A

Inside the channel.

29
Q

What can the barbiturate/anaesthetic binding site be used for?

A

It can be used for drug use to increase the activity of the GABA receptor - prolong the time the channel stays open.

30
Q

What are neurosteroids?

A

They are derivatives of sex hormones that can increase of decrease GABA inhibition.

31
Q

What does the channel blocking site do in the GABAa receptor?

A

It binds non-competitive agonists.

32
Q

What drugs can bind to the channel blocking site?

A

Picrotoxin, pentyleneterazole which can block CL- permeability.

33
Q

What can the benzodiazepine binding site be used for?

A

Used for antidepressants such as diazepam, lorazepam. They potentiate GABA and increase the frequency of the channel opening.

34
Q

What do GABAb receptors do?

A

They presynapticalaly close calcium channels to reduce transmitter release.

35
Q

What are the agonists of GABAb receptors?

A

GABA and baclofen.

36
Q

What are the antagonists of GABAb receptors?

A

2-hydroxy-saclofen and CGP55845A.

37
Q

What are GABAb receptors linked to in postsynpatic neurones?

A

K+ channels.

38
Q

What are GABAb receptors linked to in presynaptic terminals?

A

Ca2+ channels.

39
Q

What effect do GABAb receptors have presynaptically?

A

They close calcium channels to reduce transmitter release.

40
Q

What effect do GABAb receptors have postsynaptically?

A

They open potassium channels eliciting a slow hyperpolarization.

41
Q

What does it mean that GABAb receptors are obligatory heterodimers?

A

There are two types - GABAbR1 and GABAbR2 that are non-functional alone. When they are both present, they dimerize via a C terminal to form a functional GABAbR.

42
Q

Where are the two GABAb receptors found?

A

GABAbR1 in the endoplasmic reticulum and GABAbR2 in the cell membrane.

43
Q

How do the GABAbR receptors combine if they are in different locations?

A

When both receptors are present, R2 traffics R1 to the cell surface.

44
Q

What agonists of GABAbR receptors can be used therapeutically?

A

Multiple sclerosis and related motor disorders. They activate postsynaptic GABABbR receptors on motor neurones.

45
Q

What can GABAbR antagonists be used for therapeutically?

A

Epilepsy - block presynaptic GABAbR on GABA neurones to prevent reduction of GABA release and increase synaptic inhibition.

PA20023 (17 decks)

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