GABA Flashcards
What does GABA do? Basic
It is the major inhibitory neurotransmitter in the CNS
What percentage of synapses does GABA-A receptors make up in the brain?
20-50% of synapses in the brain
What is GABA-As mechanism of action?
It binds to GABA by opening a transmembrane channel that is permeable to chloride. Supressing neuronal activity in the brain
What is the predominant synaptic GABA isoform?
A1B2Y2
Which sub-unit interface does GABA bind to?
beta-alpha interface
Which sub-unit interface does benzodiazepines bind to?
alpha-gamma interface
What superfamily does GABA-A receptors belong to?
Cys loop ligand-gated ion channel
How many GABA subunits are there in humans?
19
List all human GABA subunits
A1-6 (6), B1-3 (3), G1-3 (3), Rho1-3 (3), Epsilon (1), Delta (1), Pie (1), Theta (1)
Where are GABA-A receptors known to localise in the synapse?
In both postsynaptic sites and extrasynaptic sites
How do GABA-A receptors function at the postsynaptic site?
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
How do GABA-A receptors function at the extrasynaptic sites?
Low ambient GABA concentrations open GABA-A receptors for a longer period
What ions are GABA-A mostly selective for?
Chloride ions, with some permeability for bicarbonate anions
How are GABA-A receptors modulated?
Post-translational modification
Where do benzodiazepines bind?
High-affinity binding site located at the A/Y subunit interface in the homologous position to the agonist site
What is the mechanism of action for benzodiazepines?
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
Name an additional exogenous modulator of GABA
Ethanol
What location in the brain is GABA named as the major inhibitory neurotransmitter?
Cerebral cortex
Where is GABA formed?
GABAergic axon terminals
How is GABA formed?
Transamination of a a-ketoglutarate to glutamic acid, which is then decarboxylated by gluamic acid decarboxylase (GAD) to GABA
Describe the GABA-A receptor complex
Pentameric heterooligomer that contains binding sites for GABA, barbituates, benzodiazepines, and neurosteriods
How does GABA-B receptors work?
Hyperpolarise the neuron by increasing potassium conductance
