D1 GABA

Question 1

What is GABAs full name
how is GABA synthesized
where is GABA located

Answer 1

Gamma-aminobutyric acid
Conversion of glutamate via GAD (glutamine decarboxylase) –> GABA
- located: CNS: striatum, substantia niagra, hippocampus, globus pallidus etc.

Question 2

what criteria must a chemical meet to be classes as a neurotransmitter

Answer 2

1. Synthesised within neurone
2. Stored in nerve terminal
3. Released by nerve stimulation in Ca2+ dependent manner
4. Exogenous drug must mimic endogenous neurotransmitter
5. Antagonist must inhibit neurotransmitter & exogenous drug
6. Specific mechanisms exist for inactivation

Question 3

where is GABA

• synthesized
• how is it removed (by which two methods) & (what is the variants of transporters)

Answer 3

Formed in nerve terminals from glutamate
1. GABA transporter (GAT) terminates synaptic action
GAT variants: GAT1, GAT2, GAT3 and BGT1

2. Na ion symporter
   Na ions down conc gradient & GABA up (E dependent transport)
   - in neuronal (GAT1, GAT3) and non-neuronal (GAT2, BGT1) tissue

Question 4

which location is GABA catalyzed

- what is it converted to?

Answer 4

neuronal and non-neuronal tissue

- converted to succinate by GABA transaminase (GABA-T) (destroys GABA)

Question 5

what are the 2 main classes of binding sites of GABA

Answer 5

1. GABA receptors
   binding is NOT Na-dependent

2. GABA uptake site
(more Na uptake sites than GABA)
greatly outnumber GABA receptor sites
neuronal & non-neuronal
binding IS Na-dependent

Question 6

Name GABA receptor subtypes

Answer 6

1. GABAa
   - bicuculline-sensitive
   - baclofen-insensitive
2. GABAb
   - bicuculline-insensitive
   - baclofen-sensitive

Question 7

what does GABAa activation lead to

GABAb activation

Answer 7

GABAa activation leads to opening of Cl channel = movement of Cl ions across the cell membrane which stabilises the membrane and renders it unexcitable to other input - thats why it is inhibitory

GABAb - GCRP activation leads to activation of 2 protein & to changes in intracellular conc of 2nd messengers molecules - which can lead to cellular effects

Question 8

Describe the structure of GABAa complex

Answer 8

Ligand-gated chloride ion channel
Pentameric (5 subunits)
Subunits are standard 4TM structure (polypeptide crosses membrane 4 times)

Question 9

describe the role of GABA

where it is inhibitory

Answer 9

An inhibitor which suppresses neuronal activation

• inhibitory synaptic neurotransmitter: suppresses neuronal activation
• presynaptic inhibition: axo-axonal inhibition
• post synaptic inhibition: recurrent inhibition

inhibitory in the spinal cord

Question 10

describe recurrent inhibition

• what happens at axon co-lateral
• what does it prevent
• drug effects which enhance and depress

Answer 10

1. Stimulate incoming pathway: excitation followed by inhibition of outgoing pathway
2. from axon of pyramidal cell activates GABA interneuron which inhibits firing of pyramidal cell
3. Prevents bursting discharge: reduces maximum firing rate of pyramidal cell (bursting discharge is a feature of epilepsy (anticonvulsive)
   Drug effects
   - GABA agonists (muscimol) – enhance RI
   - GABA antagonists (bicuculline) – depress RI