Chapter 8 Part 2: GABA Flashcards
What is GABA?
GABA is the main inhibitory amino acid neurotransmitter in the brain. It is co-expressed and co-released with other classical neurotransmitters like glutamate, glycine, acetylcholine, and dopamine.
How is GABA synthesized?
It is synthesized from glutamate by the enzyme glutamic acid decarboxylase (GAD).
How is GABA packaged into synaptic vesicles?
It is taken up into synaptic vesicles by the transporter protein called vesicular GABA transporter (VGAT aka VIAAT). VGAT also transports glycine into synaptic vesicles.
How is GABA inactivated?
reuptake and metabolism by neurons and astrocytes
How is GABA taken up by neurons and astrocytes?
By transporters called GAT-1, GAT-2, and GAT-3. GAT-1 and GAT-2 are found on both neurons and astrocytes but GAT-3 is only found on astrocytes.
How do neurons metabolize GABA?
The enzyme GABA aminotransferase (GABA-T) converts GABA into the products glutamate and succinate.
How do astrocytes metabolize GABA?
The enzyme GABA aminotransferase (GABA-T) converts GABA into the products glutamate and succinate (same as with neurons).
Then the enzyme glutamine synthetase converts glutamate into glutamine. The glutamine can be released by the astrocyte, taken up by neurons, converted back to glutamate by the enzyme glutaminase, and resynthesized into GABA for reuse.
What is the structure of the GABA-A receptor?
The GABA-A receptor is an ionotropic receptor containing 5 subunits. A GABA-A receptor complex may contain a combination of 3-4 different kinds of subunits. The subunits form an ion channel that permits chlorine (Cl-) ions to move across the cell membrane.
How does the GABA-A receptor function?
Typically, Cl- moves from outside the cell to inside the cell causing inhibition of the postsynaptic cell due the membrane hyperpolarization. It is also possible for Cl- ions to move from inside the cell to outside the call causing membrane depolarization and cellular excitation (instead of inhibition).
What are anxiolytic drugs?
Anxiolytic drugs have an anti-anxiety profile.
How do anxiolytic drugs work?
The GABA-A receptor is sensitive to certain anxiolytic drugs that depress the central nervous system (e.g. BDZ, barbiturates, ethanol). The principle mechanism of action is positive allosteric modulation of the GABA-A receptor. This has the effect of potentiating GABA-mediated synaptic inhibition. These anxiolytic drugs interact with additional modulary sites on the GABA receptor that are distinct from the GABA binding site.
What is the structure of the GABA-B receptor?
The GABA-B receptor is metabotropic receptor made up of two subunits. GABA-B receptors are located both post- and presynaptically.
How do GABA-B postsynaptic receptors function?
The postsynaptic receptors stimulate potassium ion channel opening and have the effect of inhibiting neuronal firing.
How do GABA-B presynaptic receptors function?
The presynaptic receptors inhibit calcium ion channel opening and have the effect of reducing neurotransmitter release from the nerve terminal. They also inhibit cAMP formation. Presynaptic GABA-B receptors can act as with autoreceptors or heteroreceptors.
Where is GABA found?
- GABAergic neurons may function as interneurons (e.g. in the cortex and hippocampus).
- They can also function as projection neurons (e.g. from the striatum to the globus pallidus and substantia nigra.
