Neurotransmitter Systems II : GABA & Glycine

Question 1

What is the criteria for being a neurotransmitter?

Answer 1

→ 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

Question 2

What are the two main methods that inhibitory neurotransmitters use?

Answer 2

→ Influx of negative ions via chloride channels

→ Efflux of positive ions via potassium channels

Question 3

Describe the conversion from Glutamate to GABA?

Answer 3

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

Question 4

How is GABA transported into vesicles?

Answer 4

→ VIAAT

→ vesicular inhibitory amino acid transporters

Question 5

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

Answer 5

→ Glutamate vesicles are round

→ GABA or glycine vesicles are more oval in shape

Question 6

Where are GABA A receptors found?

Answer 6

→ Postsynaptically

→ They can sometimes be found presynaptically on glia

Question 7

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

Answer 7

→ GABA transaminase

→ can diffuse away from the synapse

Question 8

Between what two receptors does GABA bind?

Answer 8

→ Alpha and beta receptors

Question 9

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

Answer 9

→ 2 molecules

Question 10

Where is the benzodiazepine binding site found?

Answer 10

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

Question 11

What are channel modulators?

Answer 11

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

Question 12

What is an example of a GABA A channel blocker?

Answer 12

→ Picrotoxin

Question 13

What type of G protein is a GABA B receptor?

Answer 13

→ Gi protein channel

Question 14

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

Answer 14

→it opens K+ channels so it hyperpolarizes

Question 15

What is another effect of the GABA B receptor?

Answer 15

→ It blocks Ca2+ channels

Question 16

What are the 4 types of GABA A receptor enhancers?

Answer 16

→ Barbiturates
→ Benzodiazepines
→ Progesterone
→ Ganaloxone

Question 17

What is an example of a GABA transaminase inhibitor?

Answer 17

→ Vigabatrine

Question 18

How do the majority of epileptics work?

Answer 18

→ Increasing inhibition

→ Enhance the currents through GABA A

Question 19

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

Answer 19

→ GAT

Question 20

Describe the steps for glycine synthesis?

Answer 20

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

Question 21

What are the subtypes of glycine receptors?

Answer 21

→ alpha 1 - 4

→ one beta subtype

Question 22

How is glycine activity terminated?

Answer 22

→ Reuptake by glycine transporter GlyT

Question 23

What breaks down glycine?

Answer 23

→ serine hydroxymethyl-transferase

→ or it diffuses away from the synapse

Question 24

Why is glycine difficult to target?

Answer 24

→ It is present on inhibitory receptors

→ Glycine is also needed for NMDA receptors which are excitatory

Question 25

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

Answer 25

→ Inhibitory and excitatory pathways are activated

Question 26

What are the 4 glutamate receptors?

Answer 26

→ AMPA → NMDA → Kainate → MGlu R1-8s

Question 27

In what 2 ways can glutamate be terminated?

Answer 27

→ Diffusion | → EAATs

Question 28

What are the 2 GABA receptors?

Answer 28

→ GABA A | → GABA B

Question 29

In what 3 ways can GABA be terminated?

Answer 29

→ Diffusion → GAT → Enzyme

Question 30

What is the glycine receptor?

Answer 30

→ Glycine R

Question 31

In what 3 ways can glycine be terminated?

Answer 31

→ Diffusion, GlyT, enzyme

Question 32

What is the serotonin receptor?

Answer 32

→ 5-HT 1-7

Question 33

What are the 3 ways serotonin can be terminated?

Answer 33

→ Diffusion → SERT → enzyme

Question 34

What are the dopamine receptors?

Answer 34

→ D1-D5

Question 35

What are the 3 ways that dopamine can be terminated?

Answer 35

→ Diffusion → DAT → Enzyme

Question 36

What are the 2 receptors for ACh?

Answer 36

→ nAChR | → mAChR

Question 37

What kind of a receptor is GABA A?

Answer 37

→ ligand gated Cl-

Question 38

What are the subunits of a GABA A receptor?

Answer 38

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

Question 39

What is the typical configuration of a GABA A receptor?

Answer 39

→ pentameric structure | → 2 alpha, 2 beta and 1 gamma

Question 40

What are the components of the GABA B receptor?

Answer 40

→ GABAB 1 and GABA B2

Question 41

What are the two types of GAT?

Answer 41

→ GAT1 is in neurons | → GAT 3 is in glial cells

Question 42

How is GABA degraded?

Answer 42

→ GABA → succinic semialdehyde catalysed by gaba transaminase → succinic semialdehyde → succinic acid catalysed by succinic semialdehyde dehydrogenase (SSADH)

Question 43

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

Answer 43

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

Question 44

How is glycine transported into vesicles?

Answer 44

→ VIAAT

Question 45

What is the most common configuration of the glycine receptor

Answer 45

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

Question 46

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

Answer 46

→ Glyt1 - glial cells | → Glyt2 - neurons

Question 47

Where are glycine receptors found?

Answer 47

→ Pre and post synaptically

Question 48

What is hyperekplexia?

Answer 48

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

Question 49

How does hyperekplexia work?

Answer 49

→ no glycine protein at the postsynaptic membrane

Question 50

What are the noradrenaline receptors?

Answer 50

→ alpha 1 and 2 | → beta 1 and 2

Question 51

What are the three ways noradrenaline is terminated?

Answer 51

→ NERT → enzyme → diffusion