GABA Flashcards
What is the function of GABA?
Primary inhibitory transmitter in the brain
GABA transmission plays numerous roles in brain function:
Acts as a filter for information coming into neurons (cortical neurons are often bombarded by numerous excitatory inputs from other parts of the cortex, limbic system, etc., so GABA help to filter out what’s important vs what’s not)
Regulates different patterns of firing in cortex (e.g.; GABA aids the transition from single spike to burst mode firing)
Reduced GABA activity promotes seizures
Many brain circuits are set up as a series of inhibitory GABAergic connections- works through a process of disinhibition
What neurons use GABA?
All medium spiny neurons in striatum and other nuclei with the basal ganglia
Projection neurons intermixed within monoamine cell groups (DA, 5-HT).
Interneurons in cerebral cortex (30% of all neurons), hippocampus, amygdala and most other brain regions
How is GABA synthesized? Which neurons synthesize it?
Synthesized from glutamate by glutamate decarboxylase (GAD)
GABA is only synthesized in GABA neurons, so GAD serves as a good marker for these cells
How is GABA moved into vesicles?
The vesicular GABA transporter (VGAT) move GABA into vesicles
How is GABA removed from the synaptic cleft?
GABA is removed from the synaptic cleft by reuptake transporters: GAT-1 through 3.
Where are the different GABA reuptake transporters located?
GAT-1 can be located on presynaptic terminals, whereas all 3 transporters are on astrocytes that mop up GABA in a similar manner to glutamate
How is GABA metabolized?
GABA is metabolized to glutamate and succinate by GABA aminotransferase (GABA-T)
In astrocytes, the glutamate is converted to glutamine by glutamine synthetase.
What happens to the glutamine that is being stored in astrocytes (after GABA is uptaken and converted)?
Glutamine can be released by astrocytes, taken up by neurons, converted back to glutamate, and used to remake GABA.
List the two main GABA receptor subtypes
GABA-A (ionotropic) and GABA-B (metabotropic)
What is the GABA-A receptor?
GABA-A is an ionotropic GABA receptor subtype: allow Cl (negatively charged ion that is present in higher concentrations outside the cell) to move from outside inside the cell = hyperpolarization.
How many subunits does GABA-A consist of?
Each receptor consists of five subunits, of various combinations of four types—α (alpha), β (beta), γ (gamma), δ (delta).
Where can drugs bind to affect GABA-A function?
GABA-A receptors have multiple sites where drugs/other molecules can bind to affect its function:
- GABA binding site
- Inside channel pore
What is muscimol?
An agonist that acts on GABA-A receptor by binding to the GABA binding site. It is used in experiments for reversibly inactivations fo brain regions. It was used as a hallucinogen in the past.
What is bicuculline?
A competitive antagonist that acts on GABA-A receptor by binding to the GABA binding site. It prevents GABA from activating the receptor and has no effect on activating the receptor and can induce seizures. Use experimentally primarily for understanding GABA-A function.
What is picrotoxin?
A non-competitive antagonist that acts on GABA-A receptor by binding to the inside channel pore which blocks the receptor and prevents ions from flowing through. It’s non-competitive because it’s disrupting the receptor function at a site separate from the GABA binding site.
