GABA

Question 1

What does GABA do? Basic

Answer 1

It is the major inhibitory neurotransmitter in the CNS

Question 2

What percentage of synapses does GABA-A receptors make up in the brain?

Answer 2

20-50% of synapses in the brain

Question 3

What is GABA-As mechanism of action?

Answer 3

It binds to GABA by opening a transmembrane channel that is permeable to chloride. Supressing neuronal activity in the brain

Question 4

What is the predominant synaptic GABA isoform?

Answer 4

A1B2Y2

Question 5

Which sub-unit interface does GABA bind to?

Answer 5

beta-alpha interface

Question 6

Which sub-unit interface does benzodiazepines bind to?

Answer 6

alpha-gamma interface

Question 7

What superfamily does GABA-A receptors belong to?

Answer 7

Cys loop ligand-gated ion channel

Question 8

How many GABA subunits are there in humans?

Answer 8

19

Question 9

List all human GABA subunits

Answer 9

A1-6 (6), B1-3 (3), G1-3 (3), Rho1-3 (3), Epsilon (1), Delta (1), Pie (1), Theta (1)

Question 10

Where are GABA-A receptors known to localise in the synapse?

Answer 10

In both postsynaptic sites and extrasynaptic sites

Question 11

How do GABA-A receptors function at the postsynaptic site?

Answer 11

Synaptic transmission leads to the release of GABA, opening GABAA receptor chloride channels. This causes a short (millisecond) increase in anion conductance, resulting in the hyperpolarisation of a depolarised membrane

Question 12

How do GABA-A receptors function at the extrasynaptic sites?

Answer 12

Low ambient GABA concentrations open GABA-A receptors for a longer period

Question 13

What ions are GABA-A mostly selective for?

Answer 13

Chloride ions, with some permeability for bicarbonate anions

Question 14

How are GABA-A receptors modulated?

Answer 14

Post-translational modification

Question 15

Where do benzodiazepines bind?

Answer 15

High-affinity binding site located at the A/Y subunit interface in the homologous position to the agonist site

Question 16

What is the mechanism of action for benzodiazepines?

Answer 16

Benzodiazepines bind to their recognition site, causing a conformational change in the receptor. This increases the affinity for channel gating by GABA at both sites. This increases the mean opening time of the channels

Question 17

Name an additional exogenous modulator of GABA

Answer 17

Ethanol

Question 18

What location in the brain is GABA named as the major inhibitory neurotransmitter?

Answer 18

Cerebral cortex

Question 19

Where is GABA formed?

Answer 19

GABAergic axon terminals

Question 20

How is GABA formed?

Answer 20

Transamination of a a-ketoglutarate to glutamic acid, which is then decarboxylated by gluamic acid decarboxylase (GAD) to GABA

Question 21

Describe the GABA-A receptor complex

Answer 21

Pentameric heterooligomer that contains binding sites for GABA, barbituates, benzodiazepines, and neurosteriods

Question 22

How does GABA-B receptors work?

Answer 22

Hyperpolarise the neuron by increasing potassium conductance