GABA Flashcards

1
Q

What is the major inhibitory NT in the brain?

A

GABA

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2
Q

What kind of receptors can GABA activate?

A

Ionotropic and Metabotropic

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3
Q

How is GABA synthesised?

A

Enzymatically via the krebs cycle

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4
Q

What molecule is used to synthesise GABA in the krebs cycle?

A

glucose

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5
Q

Where is GABA synthesised?

A

Nerve terminal

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6
Q

What is the direct precursor to GABA?

A

Glutamate

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7
Q

Which enzyme converts glutamate to GABA?

A

Glutamic acid decarboxylase

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8
Q

Where are GABA transporters found?

A

Astrocytes and presynaptic nerve terminals

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9
Q

If the GABA isn’t recycled, what is it converted to in the presynaptic terminal?

A

Succinic semialdehyde

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10
Q

Which enzyme converts GABA to succinic semialdehye?

A

GABA transaminase

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11
Q

What is succinic semialdehyde an intermediate of?

A

Krebs cycle

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12
Q

What happens to GABA once it is reuptaken by astrocytes?

A

Converted to succinic semialdehyde

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13
Q

In which brain areas is GABA found?

A

Cerebellum, basal ganglia, hippocampus, hypothalamus, cortex

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14
Q

In which type of neurons is GABA is principally found?

A

local interneurones

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14
Q

What could happen if the glutamate GABA balance gets out of control?

A

Seizures and epilepsy

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15
Q

How does a neuron having multiple synapses on its dendrites affect the APs it may/may not fire down its axon?

A

It sums all the potentials from them (e.g. +ve from glutamate, -ve from GABA) and then fires the AP depending on the overall potential

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16
Q

What kind of receptor is GABAa?

A

Ligand gated ion channel

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17
Q

What kind of receptor is GABAb?

A

GPCR

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18
Q

Where are GABAa receptors generally found?

A

postsynaptically

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19
Q

Where are GABAb receptors generally found?

A

pre and postsynaptically

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20
Q

What speed of inhibition does GABAa receptors mediate?

A

fast

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21
Q

What speed of inhibition does GABAb receptors mediate?

A

slow

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22
Q

To which ion is the GABAa ion channel permeable to?

A

Cl-

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23
Q

Which ion channels can be regulated as a result of the GPCR receptor GABAb?

A

Ca2+ and K+

24
Which GABA receptor can inhibit transmitter release?
GABAb
25
Why do GABAb receptors exhibit a slow inhibition?
Second messenger systems take time
26
What does the K+ Cl- transporter do?
Transports K+ and CL- out of the postsynaptic neuron
27
What is the result of the K+ Cl- transporter?
A low conc of Cl- is maintained within the cell (maintains conc grad)
28
How many subunits make up the GABAa receptor?
5
29
How many transmembrane domains does each GABAa subunit have?
4
30
What is the role of the transmembrane 2 domain on the GABAa?
Pore forming segment
31
What is the subunit makeup of a GABAa receptor?
2 alpha, 2 beta, 1 gamma
32
Where does GABA bind on GABAa?
Interface between alpha and beta subunit
33
Why isnt there 3 GABAa binding sites?
The orientation of one of the alpha beta interfaces is incorrect so it cant be used as a binding site
34
Which subunit do the δ, ε, π, θ and ρ take the place of?
gamma
35
What is dependent on the subunit composition of GABAa receptors?
The inhibitory effect and the spatial distribution of the receptors
36
GABA agonists?
Muscimol, GABA
37
GABA antagonists
bicuculline, gabazine
38
What effect does the barbiturate/anesthetic binding site have on the GABAa receptor?
Prolong open time of channel
39
What effect does the neurosteroid binding site have on the GABAa receptor?
Increase or decrease endogenous GABA inhibition
40
Which molecules can bind to the GABAa channel blocking site?
Picrotoxin, pentylenetetrazole
41
What effect does the channel blocking binding site have on the GABAa receptor?
block cl- permeability
42
What effect does the benzodiazepine binding site have on the GABAa receptor?
increase frequency of channel opening
43
What are GABAb receptors coupled to?
G alpha i/o
44
What do GABAb receptors negatively regulate?
Adenyl cyclase and cyclic amp
45
GABAb receptor agonists?
GABA, baclofen
46
What do G beta gamma subunits regulate?
Ion channels
47
What does the g beta gamma subunit do presynaptically?
Closes calcium ion channels
48
What do GABAb receptors do postsynaptically?
Open K+ channels, allowing K+ to leave the cell thus hyperpolarising the postsynaptic neuron
49
How many subunits are required to make a GABAb receptor?
2
50
Where is GABAbR1?
In the ER
51
Where is GABAbR2?
In the cell membrane
52
What happens if there is a GABAbR2 that needs to be expressed in the cell surface?
GABAbR1 travels to the cell surface
53
When GABAbR1 and 2 are expressed at the CSM, what type of interaction do their cytoplasmic domains form?
A coil-coil interaction
54
Which subunit on GABAb does GABA bind to?
GABAbR1
55
What is baclofen used to treat?
muscle spasticity
55
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