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
Q

How does the GABAb receptor work?

A

Binding stimulates the Gi/O pathway

26
Q

What does activation of the Gi/O pathway cause?

A

Activates adenylyl cyclase to reduce cAMP levels, which activates potassium channels, causing an effluent

27
Q

What are the two ways in which hyperpolarisation can happen?

A

Influx of calcium or efflux of potassium

28
Q

How much of the brains volume does the cerebellum account for?

A

10%

29
Q

What is the function of the cerebellum?

A

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
Q

What are purkinje cells?

A

A class of GABAergic neurons that comprise the principle projection neurons of the cerebellar cortex

31
Q

What do the purkinje cells dendritic trees receive?

A

Convergent input from cells in the molecular layer

32
Q

What do the purkinje cells dendritic trees send out?

A

GABAergic projections to Deep cerebellar neurons

33
Q

What does the GABAergic projection to the deep cerebellar neurons generate?

A

An error connection signal that can modify movements

34
Q

What do GABA projections in the cerebellum provide the basis for?

A

Real time control of precise and synchronous movement

35
Q

What two things work together to control the brains overall level of excitation?

A

GABA and glutamate

36
Q

What is epilepsy?

A

Brain disorder characterised by periodic and unpredictable seizures mediated by the rhythmic firing of large groups of neurons

37
Q

How do epilepsy drugs work?

A

Increase inhibition by increasing GABA

38
Q

What is glycine?

A

Major inhibitory neurotransmitter in the CNS

39
Q

Where is glycine most commonly found?

A

In the ventral ramus Which is the location for spinal interneuron terminals

40
Q

What is the precursor to glycine?

A

Serine

41
Q

What catalyses serine -> glycine?

A

Serine hydroxymethyltransferase

42
Q

Where is glycine synthesised?

A

Nerve terminals

43
Q

What class of enzymes causes the reuptake of glycine?

A

GlyT 1 and 2

44
Q

What enzyme is glycine -> serine catalysed by?

A

Serine hydroxymethyl

45
Q

What type of receptor does glycine bind to?

A

Ligand gated ion channel

46
Q

What happens when glycine binds to its receptor?

A

Allows chloride ions into the neuron, leading to hyperpolarisation

47
Q

What different subtypes of the glycine receptor are there?

A

4 alpha, one beta

48
Q

What are the most common glycine LGIC configurations?

A

3 alpha, 2 beta or 4 alpha, 1 beta

49
Q

What potently blocks glycine receptors?

A

Plant alkaloid strychnine

50
Q

What is hyperekplexia?

A

A rare disorder characterised by hypertonic and increased muscle tone

51
Q

What can hyperekplexia lead to?

A

Neuronal hyperexcitability and hypertonic and an exaggerated startle response

52
Q

Why do the fainting goats faint?

A

Decreased muscle chloride conductance, which can be caused by glycine receptor mutations