Neurotransmitter Systems II : GABA & Glycine Flashcards

1
Q

What is the criteria for being a neurotransmitter?

A

→ The molecule must be synthesized and stored in a presynaptic neuron
→ The molecule must be released by the presynaptic axon terminal upon stimulation
→ the molecule must produce a response in the post synaptic cell

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2
Q

What are the two main methods that inhibitory neurotransmitters use?

A

→ Influx of negative ions via chloride channels

→ Efflux of positive ions via potassium channels

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3
Q

Describe the conversion from Glutamate to GABA?

A

→ Carboxylic acid group is removed from glutamate to make GABA
→ vitamin B6 (pyridoxal phosphate) acts as a cofactor

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4
Q

How is GABA transported into vesicles?

A

→ VIAAT

→ vesicular inhibitory amino acid transporters

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5
Q

What is the difference in shape between glutamate, GABA and glycine vesicles?

A

→ Glutamate vesicles are round

→ GABA or glycine vesicles are more oval in shape

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6
Q

Where are GABA A receptors found?

A

→ Postsynaptically

→ They can sometimes be found presynaptically on glia

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7
Q

What are the two ways that GABA can be broken down?

A

→ GABA transaminase

→ can diffuse away from the synapse

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8
Q

Between what two receptors does GABA bind?

A

→ Alpha and beta receptors

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9
Q

How many molecules of GABA are needed for the GABA A channels to open?

A

→ 2 molecules

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10
Q

Where is the benzodiazepine binding site found?

A

→ At the alpha and gamma interface of the GABA A receptor

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11
Q

What are channel modulators?

A

→ They increase the conductance of chloride through the GABA A channels such as alcohol

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12
Q

What is an example of a GABA A channel blocker?

A

→ Picrotoxin

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13
Q

What type of G protein is a GABA B receptor?

A

→ Gi protein channel

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14
Q

What is one of the major effects of the GABA B receptors?

A

→it opens K+ channels so it hyperpolarizes

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15
Q

What is another effect of the GABA B receptor?

A

→ It blocks Ca2+ channels

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16
Q

What are the 4 types of GABA A receptor enhancers?

A

→ Barbiturates
→ Benzodiazepines
→ Progesterone
→ Ganaloxone

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17
Q

What is an example of a GABA transaminase inhibitor?

A

→ Vigabatrine

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18
Q

How do the majority of epileptics work?

A

→ Increasing inhibition

→ Enhance the currents through GABA A

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19
Q

What is the transporter that takes GABA to the presynaptic terminal?

A

→ GAT

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20
Q

Describe the steps for glycine synthesis?

A
3-phosphoglycerate (glycolysis)
              ↓
         serine (serine hydroxy methyl transferase)
              ↓
         glycine
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21
Q

What are the subtypes of glycine receptors?

A

→ alpha 1 - 4

→ one beta subtype

22
Q

How is glycine activity terminated?

A

→ Reuptake by glycine transporter GlyT

23
Q

What breaks down glycine?

A

→ serine hydroxymethyl-transferase

→ or it diffuses away from the synapse

24
Q

Why is glycine difficult to target?

A

→ It is present on inhibitory receptors

→ Glycine is also needed for NMDA receptors which are excitatory

25
Q

What gets activated if you use an agonist that has a similar shape to glycine?

A

→ Inhibitory and excitatory pathways are activated

26
Q

What are the 4 glutamate receptors?

A

→ AMPA
→ NMDA
→ Kainate
→ MGlu R1-8s

27
Q

In what 2 ways can glutamate be terminated?

A

→ Diffusion

→ EAATs

28
Q

What are the 2 GABA receptors?

A

→ GABA A

→ GABA B

29
Q

In what 3 ways can GABA be terminated?

A

→ Diffusion
→ GAT
→ Enzyme

30
Q

What is the glycine receptor?

A

→ Glycine R

31
Q

In what 3 ways can glycine be terminated?

A

→ Diffusion, GlyT, enzyme

32
Q

What is the serotonin receptor?

A

→ 5-HT 1-7

33
Q

What are the 3 ways serotonin can be terminated?

A

→ Diffusion
→ SERT
→ enzyme

34
Q

What are the dopamine receptors?

A

→ D1-D5

35
Q

What are the 3 ways that dopamine can be terminated?

A

→ Diffusion
→ DAT
→ Enzyme

36
Q

What are the 2 receptors for ACh?

A

→ nAChR

→ mAChR

37
Q

What kind of a receptor is GABA A?

A

→ ligand gated Cl-

38
Q

What are the subunits of a GABA A receptor?

A

→ Six alpha subtypes (a1-6)
→ three beta subtypes (b1-3)
→ three gamma subtypes ( y1-3)
→ also delta, epsilon, pi and theta subunits

39
Q

What is the typical configuration of a GABA A receptor?

A

→ pentameric structure

→ 2 alpha, 2 beta and 1 gamma

40
Q

What are the components of the GABA B receptor?

A

→ GABAB 1 and GABA B2

41
Q

What are the two types of GAT?

A

→ GAT1 is in neurons

→ GAT 3 is in glial cells

42
Q

How is GABA degraded?

A

→ GABA → succinic semialdehyde
catalysed by gaba transaminase

→ succinic semialdehyde → succinic acid
catalysed by succinic semialdehyde dehydrogenase (SSADH)

43
Q

What are the 5 types of drugs used to treat epilepsy?

A
→ GABA A receptor enhancers
→ GAT blockers
→ GABA transaminase inhibitor 
→ GAD modulator 
→ Prodrug
44
Q

How is glycine transported into vesicles?

A

→ VIAAT

45
Q

What is the most common configuration of the glycine receptor

A

→ 3a1 or 2 beta
OR
→ 4 alpha 1 and 1 beta

46
Q

What are the two different types of Glyt and where are they found?

A

→ Glyt1 - glial cells

→ Glyt2 - neurons

47
Q

Where are glycine receptors found?

A

→ Pre and post synaptically

48
Q

What is hyperekplexia?

A

→ Disorder characterised by increased mucscle tone and a exaggerated startle response

49
Q

How does hyperekplexia work?

A

→ no glycine protein at the postsynaptic membrane

50
Q

What are the noradrenaline receptors?

A

→ alpha 1 and 2

→ beta 1 and 2

51
Q

What are the three ways noradrenaline is terminated?

A

→ NERT
→ enzyme
→ diffusion