GABA AND glycine

Question 1

How is glutamate synthesised?

Answer 1

glutamate metabolized by glutamic acid decarboxylase and pyridoxalphosphate (Vit B6)

Question 2

Where is GAD found?

Answer 2

nerve terminal cytoplasm containing GABA. RATE limiting step in GANA synthesis.

Question 3

Where is GABA stored?

Answer 3

nerve terminals versicular and non vesicularly

Question 4

What is the release of GABA dependent on?

Answer 4

calcium

Question 5

How is gaba inactivated by reuptake?

Answer 5

Re uptake is sodium dependent

back into nerve terminals and glia where it is reused in terminals and metabolised for both

Question 6

How is gaba inactivated by metabolism?

Answer 6

There are two stages
GABA metabolised by GABAt in mt to succinic semialdehyde then 2nd stage is the aldehyde to succinate via succinic semialdehyde dehydrogenase

Question 7

How is GABA distributed?

Answer 7

short interneurons and long projection neurons

Question 8

What is the function of Gaba?

Answer 8

1. A direct-chloride mediated hyperpolarisation of dendrites and soma (GABAa)
2. Decreased neurotransmitter release via a K+ conductance (GABAb). Post-synaptic also
3. GABAc receptors also exist.

Question 9

What are the properties of GABAa receptor?

Answer 9

1. ligand gated ion channel
2. number of binding sites
3. results in chloride influx = hyperpolarisation

Question 10

Describe the allosteric modulatory sites of GABAa receptor

Answer 10

a) Benzodiazepine (BZ) binding site - BZ increases the affinity of GABA for its receptor and also increases the frequency of channel opening in response to GABA thereby increasing inhibition.
Flumazenil binds to BZR to block BZ effects competitively
Beta carboline binds to BZR to decrease gaba action like an inverse agonists
b) Barbiturate binding site - increases the duration of chloride channel opening in response to GABA producing an increase in inhibition.

Question 11

What is the agonist and antagonist of GABAa?

Answer 11

agonist - muscimol

antagonist - Bicuculline

Question 12

What is the function of GABAa receptor

Answer 12

epilepsy and in anxiety

GABAa antagonists produce seizures and agonists producing anticonvulsant effects

Question 13

GABAb receptors agonist and antagonist?

Answer 13

agonist - baclofen - trests spastic condition i.e. hyperexcitability of the spinal cord
antagonist - phaclofen

Question 14

GABAb properties?

Answer 14

1. G-protein-lined receptor family
2. opens potassium channel - hyperpolarisation and increased inhibition.
3. inhibits neurotransmitter release
4. located mostly pre-synaptically, but also postsynaptic.
5. many GABAb receptors in the spinal cord.

Question 15

Glycine properties?

Answer 15

1. main inhibitory neurotransmitter
2. in the spinal cord
3. chloride influx
4. inhibition by hyperpolarisation

Question 16

How is glycine synthesised?

Answer 16

serine is metabolised by serine hydroxymethyltransferase into glycine

Question 17

What is glycine release dependent on?

Answer 17

calcium

Question 18

How is glycine inactivated?

Answer 18

re-uptake into neurons and glia

Question 19

How is glycine distributed?

Answer 19

distributed in spinal cord and brainstem. It is the inhibitory transmitter of the Renshaw cells in the spine that inhibit motor neurons.

Question 20

What are the two types of glycine receptors and describe the properties.

Answer 20

Strychnine-sensitive chloride channel in spine, which mediates inhibition.
Strychnine-insensitive binding site on the NMDA receptor, acting as an excitatory co-agonist.