5.5 : Gaba and DA

Question 1

Q: What is GABA and how is it synthesised?

Answer 1

A: GABA is the major inhibitory neurotransmitter, synthesised from glutamate and removed from the synapse by transporters on presynaptic neurons and astrocytes.

Question 2

Q: What effect does GABA have on neurons?

Answer 2

A: GABA causes hyperpolarisation of neurons.

Question 3

Q: What are the three classes of GABA receptors?

Answer 3

A: GABAa, GABAb, and GABAc.

Question 4

Q: How does the GABAa receptor cause hyperpolarisation?

Answer 4

A: By opening Cl⁻ channels.

Question 5

Q: How does the GABAb receptor cause hyperpolarisation?

Answer 5

A: Indirectly opens potassium channels via G-protein signalling.

Question 6

Q: How does the GABAc receptor cause hyperpolarisation?

Answer 6

A: By causing chloride influx.

Question 7

Q: At what membrane potential are GABA receptors activated?

Answer 7

A: At the physiological resting potential of -65 mV.

Question 8

Q: What is the effect of GABA at a hyperpolarised resting membrane (e.g., in epilepsy)?

Answer 8

A: It can cause depolarisation at -80 mV.

Question 9

Q: Where are GABAa receptors located and what is their function?

Answer 9

A: Post-synaptically and extra-synaptically, mediating fast and tonic inhibition.

Question 10

Q: How are extra-synaptic GABAa receptors activated?

Answer 10

A: Through excess presynaptic GABA release, also called volume transmission.

Question 11

Q: What makes GABAc receptors unique compared to GABAa and GABAb?

Answer 11

A: They are insensitive to typical GABA blockers.

Question 12

Q: Where are GABAc receptors expressed?

Answer 12

A: In the retina and axonally on bipolar cells.

Question 13

Q: What is the role of GABAc receptors?

Answer 13

A: The role is unclear but possibly involved in pain and myopia.

Question 14

Q: Where are GABAb receptors located?

Answer 14

A: On glial cells and pre/post-synaptic neurons.

Question 15

Q: How do GABAb receptors work presynaptically?

Answer 15

A: They inhibit presynaptic neurons by decreasing calcium-dependent neurotransmitter release.

Question 16

Q: How do GABAb receptors work postsynaptically?

Answer 16

A: They activate potassium channels, causing slow hyperpolarisation.

Question 17

Q: Can GABAb receptor effects reverse?

Answer 17

A: Yes, under pathological conditions.

Question 18

Q: How many subtypes of GABA transporters are there?

Answer 18

A: Four: GAT1-3 and BGT1.

Question 19

Q: Where is GAT1 located?

Answer 19

A: On presynaptic terminals, axon segments, and glial cells.

Question 20

Q: Where is GAT3 located?

Answer 20

A: On glial cells.

Question 21

Q: What ions are co-transported with GABA by GAT transporters?

Answer 21

A: 2 Na⁺ and 1 Cl⁻.

Question 22

Q: What is BGT1?

Answer 22

A: Betaine GABA transporter 1.

Question 23

Q: What type of neurotransmitter is dopamine (DA)?

Answer 23

A: A monoamine neurotransmitter from the catecholamine group.

Question 24

Q: What is dopamine’s function in the brain?

Answer 24

A: It modulates excitatory and inhibitory neurotransmission and is involved in movement, reward, and motivation.

Question 25

Q: What can impaired dopamine function cause?

Answer 25

A: Neurological disorders.

Question 26

Q: How many dopamine receptor subtypes exist?

Answer 26

A: Five: D1 to D5.

Question 27

Q: What class do D1 and D5 belong to and how do they work?

Answer 27

A: D1 class; they activate G-αs to stimulate cAMP production via adenylyl cyclase.

Question 28

Q: Where are D1 class receptors located?

Answer 28

A: Post-synaptically.

Question 29

Q: What do D1 class receptors increase?

Answer 29

A: PIP2 and downstream signalling pathways.

Question 30

Q: What class do D2, D3, and D4 receptors belong to and how do they work?

Answer 30

A: D2 class; they activate G-αi to inhibit adenylyl cyclase.

Question 31

Q: Where are D2 class receptors located?

Answer 31

A: Pre- and post-synaptically.

Question 32

Q: What is the effect of D2 class receptor activation?

Answer 32

A: Decreased Ca²⁺ currents and increased K⁺ currents.

Question 33

Q: What is the significance of presynaptic D2 receptor activation?

Answer 33

A: Provides negative feedback/autoreception and responds to lower DA levels than postsynaptic receptors.

Question 34

Q: What is L-DOPA and how does it relate to dopamine?

Answer 34

A: It is a precursor and indirect agonist for dopamine receptors used in therapy.

Question 35

Q: What is the dopamine transporter (DAT) responsible for?

Answer 35

A: Returning dopamine to the presynaptic terminal.

Question 36

Q: What ions does DAT co-transport with dopamine?

Answer 36

A: 2 Na⁺ and 1 Cl⁻.

Question 37

Q: How does cocaine affect dopamine neurotransmission?

Answer 37

A: It binds to DAT and inhibits dopamine reuptake.

Question 38

Q: How does amphetamine affect dopamine neurotransmission?

Answer 38

A: It reverses the direction of DAT and alters DA reuptake.

Question 39

Q: What do monoamine oxidase (MAO) enzymes do?

Answer 39

A: Break down monoamines and are located on the outer mitochondrial membrane.

Question 40

Q: What can happen if high-tyramine foods are consumed with MAO-B inhibitors?

Answer 40

A: A hypertensive crisis may occur.

Question 41

Q: Can a neuron release more than one neurotransmitter?

Answer 41

A: Yes, for example, neurons in the olfactory bulb release both GABA and dopamine.

Question 42

Q: How does cocaine indirectly increase dopamine activity via GABA?

Answer 42

A: Cocaine decreases GABA activity, disinhibiting dopamine neurons, leading to increased dopamine release.