Amino Acid Neurotransmitters

Question 1

Outline a common synaptic process.

Answer 1

1. Uptake of precursors
2. Synthesis of transmitter
3. Uptake into vesicles
4. Metabolism of transmitter
5. Invasion of AP
6. Ca2+ influx
7. Exocytosis of vesicles
8. Diffusion to receptors
9. Action at postsynaptic receptors
10. Diffusion away from synapse
11. Re-uptake of NT by neuron
12. Re-uptake of NT by glia
13. Action on presynaptic receptors

Question 2

What is the major EXCITATORY neurotransmitter in the CNS, and what are its transporter and vesicle?

Answer 2

GLUTAMATE

taken up from extracellular space by specific transporter:
Excitatory Amino Acid Transporters (EAAT I-V)

concentrated in vesicles in glutamatergic neurons, but not in others:
Vesicular Glutamate Transporter (VGluT)

Question 3

What is the major inhibitory neurotransmitter in the CNS, how is it synthesised, and what are its transporter and vesicle?

Answer 3

GABA

synthesised from glutamate via the cytosolic enzyme:
Glutamic Acid Decarboxylase (GAD)

taken up from extracellular space by specific transporters:
GABA Transporters (GAT I - IV)

concentrated in vesicles in GABAergic neurons, but not in others:
Vesicular Inhibitory Amino Acid Transport (VIAAT)

Question 4

What is the major INHIBITORY neurotransmitter in the CNS, how is it synthesised, and what are its transporter and vesicle?

Answer 4

GABA

synthesised from glutamate via the cytosolic enzyme:
Glutamic Acid Decarboxylase (GAD)

taken up from extracellular space by specific transporters:
GABA Transporters (GAT I - IV)

concentrated in vesicles in GABAergic neurons, but not in others:
Vesicular Inhibitory Amino Acid Transport (VIAAT)

Question 5

What is the major inhibitory neurotransmitter in the SC, how is it synthesised and what are its transport and vesicle?

Answer 5

Glycine

it is the simplest amino acid and is derived from metabolism and thereby synthesised in all cells

taken up from extracellular space by specific transporters:
Glycine Transporters (GlyT-1 and GlyT-2)

concentrated in vesicles in glycinergic neurons:
VIAAT (some neurons release both GABA and Glycine)

Question 6

What is meant by “excitatory” and “inhibitory”?

Answer 6

EXCITATORY — when NT binds to receptor on postsynaptic neuron, it allows in cations, e.g. Na+, Ca2+

INHIBITORY — when NT binds to receptor on postsynaptic neuron, it allows in anions, e.g. Cl-

Question 7

What are the two main receptor types in relation to NTs?

Answer 7

Ligand-gated ion channels (LGICs) — ionotropic

G-protein coupled receptors (GPCRs) — metabotropic

Question 8

Outline the classification of Glutamate receptors.

Answer 8

Glutamate has ionotropic and metabotropic receptors.

Ionotropic glutamate receptors are NMDA, AMPA or kainate

Metabotropic glutamate receptors are mGluRs.

Question 9

What is the main ionotropic glutamate receptor agonist?

Answer 9

L-Glutamate

Question 10

Outline the classification of GABA receptors.

Answer 10

GABA has ionotropic and metabotropic receptors.

Ionotropic GABA receptors are GABA(A) and GABA(C)

Metabotropic GABA receptors are GABA(B)
–> remember bc meta-B-otropic = GABA(B)

Question 11

Discuss the receptor pharmacology pf GABA(A).

Answer 11

MECHANISM: increased Cl- flux
COUPLING: ionophore
ENDOGENOUS AGONISTS: GABA
EXOGENOUS AGONISTS: muscimol
ANTAGONISTS: bicuculline

Question 12

Discuss the receptor pharmacology pf GABA(B).

Answer 12

MECHANISM: increased K+ flux,
decreased Ca2+ flux (cAMP)
COUPLING: G-protein
ENDOGENOUS AGONISTS: GABA
EXOGENOUS AGONISTS: baclofen
ANTAGONISTS: CGP 35348