Neurotransmitter Systems II: GABA And Glycine Flashcards

1
Q

What does GABA stand for?

A

Gamma-aminobutyric acid

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2
Q

What is GABA?

A

Major inhibitory neurotransmitter in the CNS

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3
Q

What is the main precursor to GABA?

A

Glucose

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4
Q

How does glucose turn into GABA?

A

Glucose -> glutamate, which then is turned into GABA by glutamate decarboxylase with the cofactor pyridoxal phosphatase

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5
Q

What shaped vesicles is glutamate stored in?

A

Round

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6
Q

What shaped vesicles is GABA stored in

A

Oval

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7
Q

How is GABA retaken up?

A

High affinity sodium dependant GABA transporters GAT-1 on neurons and GAT-3 on glial cells

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8
Q

What are the steps in GABA degredation (no enzymes)?

A

GABA -> succinic semialdehyde -> succinic acid

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9
Q

What enzyme catalyses GABA -> succinic semialdehyde?

A

GABA Transaminase (GABA-T)

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10
Q

What enzyme catalyses succinic semialdehyde -> succinic acid?

A

Succinic semialdehyde dehydrogenase (SSADH)

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11
Q

What type of receptors are GABAa receptors?

A

Ionotropic

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12
Q

What type of receptors are GABAb receptors?

A

Metabotropic

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13
Q

What happens upon GABA binding to GABAa receptor?

A

Channel opens and allows the influx of chloride ions

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14
Q

What are the possible GABAa receptor subunits?

A

6 alpha, 3 beta, 3 gamma, delta, epsilon, pi and theta

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15
Q

What is the most common GABAa configuration?

A

2 alpha, 2 beta and a gamma

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16
Q

Why are GABAa receptors a key drug target?

A

Multiple binding sites

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17
Q

Where do agonists/ antagonists bind on GABAa receptors?

A

Between the alpha and beta subunits

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18
Q

Where does benzodiazepine bind on GABAa receptors?

A

Between alpha and gamma subunits

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19
Q

Where do channel blockers bind on GABAa receptors?

A

Blocks the ion pore (non-competitive antagonist)

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20
Q

How do channel modulators work on GABAa receptors?

A

Increase the opening

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21
Q

What is an example of a GABAa channel blocker?

A

Picrotoxin

22
Q

Where do allosteric modulators bind on GABAa receptors?

A

The receptor

23
Q

Give an example of a GABAa allosteric modulator

A

Barbituates

24
Q

What are the heteromers of the GABAb receptor?

A

GABAb1 and GABAb2

25
How does the GABAb receptor work?
Binding stimulates the Gi/O pathway
26
What does activation of the Gi/O pathway cause?
Activates adenylyl cyclase to reduce cAMP levels, which activates potassium channels, causing an effluent
27
What are the two ways in which hyperpolarisation can happen?
Influx of calcium or efflux of potassium
28
How much of the brains volume does the cerebellum account for?
10%
29
What is the function of the cerebellum?
Helps the motor cortex to procure precise and coordinated movements- detects the differences in motor error between an intended movement and the actual movement
30
What are purkinje cells?
A class of GABAergic neurons that comprise the principle projection neurons of the cerebellar cortex
31
What do the purkinje cells dendritic trees receive?
Convergent input from cells in the molecular layer
32
What do the purkinje cells dendritic trees send out?
GABAergic projections to Deep cerebellar neurons
33
What does the GABAergic projection to the deep cerebellar neurons generate?
An error connection signal that can modify movements
34
What do GABA projections in the cerebellum provide the basis for?
Real time control of precise and synchronous movement
35
What two things work together to control the brains overall level of excitation?
GABA and glutamate
36
What is epilepsy?
Brain disorder characterised by periodic and unpredictable seizures mediated by the rhythmic firing of large groups of neurons
37
How do epilepsy drugs work?
Increase inhibition by increasing GABA
38
What is glycine?
Major inhibitory neurotransmitter in the CNS
39
Where is glycine most commonly found?
In the ventral ramus Which is the location for spinal interneuron terminals
40
What is the precursor to glycine?
Serine
41
What catalyses serine -> glycine?
Serine hydroxymethyltransferase
42
Where is glycine synthesised?
Nerve terminals
43
What class of enzymes causes the reuptake of glycine?
GlyT 1 and 2
44
What enzyme is glycine -> serine catalysed by?
Serine hydroxymethyl
45
What type of receptor does glycine bind to?
Ligand gated ion channel
46
What happens when glycine binds to its receptor?
Allows chloride ions into the neuron, leading to hyperpolarisation
47
What different subtypes of the glycine receptor are there?
4 alpha, one beta
48
What are the most common glycine LGIC configurations?
3 alpha, 2 beta or 4 alpha, 1 beta
49
What potently blocks glycine receptors?
Plant alkaloid strychnine
50
What is hyperekplexia?
A rare disorder characterised by hypertonic and increased muscle tone
51
What can hyperekplexia lead to?
Neuronal hyperexcitability and hypertonic and an exaggerated startle response
52
Why do the fainting goats faint?
Decreased muscle chloride conductance, which can be caused by glycine receptor mutations