neuro: neurotransmitter systems 2: GABA and Glycine Flashcards
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what is GABA?
gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system
GABA is most commonly found as an inhibitory neurotransmitter in local circuit inter neurons
describe GABA synthesised?
the precursor is glutamate.
it is then converted into GABA via the enzyme: glutamate decarboxylase (GAD) and help of a co factor called pyridoxal phosphate (derived from vitamin B6)
This is a decarboxylation reaction, removal of the carboxylic acid
how is GABA transported?
transported into vesicles by the vesicular inhibitory amino acid transporters VIAAT
how can you determine the neurotransmitters vesicles under an electron microscope?
-glutamate is transported into vesicles that are more round, however GABA and glycine are are present in oval vesicles.
how is GABA reuptook?
-it is important for neurotransmitters to leave the synapse, as it will continually cause action potentials. It can either be diffused itself or it has to be reuptook back into the pre synaptic neurone.
- the presynaptic neurone consists of a transporter called GAT (gaba re uptake transporters)
This allows it to take the gaba back up and recycle it.
-these transporters are sodium dependent
-the transporters have different isoforms depending on what cell they’re on:
- neurons: GAT-1
-glial cells: GAT-3
How is GABA degraded?
- GABA is converted into succinic semialdehyde via the enzyme GABA transaminase (GABA-T)
- succinic semialdehyde is converted into succinic acid via succinic semialdehyde dehydrogenase (SSADH)
what receptors can GABA bind to?
It can bind to both ionotrophic and metabotrophic GABA receptors.
describe the GABAa receptor?
the GABAa receptor is a ligand gated chloride ion channel receptor, ionotrophic
-once GABA binds, it will allow the influx of chloride ions, causing the membrane potential to become more negative, leading to hyper polarisation of the membrane which then stops an action potential from occurring, giving GABA its inhibitory nature
-the GABAa receptor is a pentameric structure, and it’s most common configuration consists of 2 alpha, 2 beta and one gamma subunit.
why is the GABAa receptor important?
-bc it is a key drug target for a number of different disorders.
-consists o multiple binding sites :
-GABA binds between rhe alpha and beta subunit of the receptor
-GABAa has a specific binding site for benzodiazepines, this is between the alpha and gamma subunits
-it also allows channel blockers to act on the receptor.
- chanelmoduators
-allosteric modulators
describe the GABAb receptor?
—it is a metabotropic receptor, G protein coupled receptor.
- gabaB receptor form dimers with each other
-once GABA binds, we get activation of the Gi/O G protein
- this allows the efflux of potassium ions, leading to a negative membrane potential, causing hyperpolarisation which stops action potentials from occurring.
- they interact with calcium channels aswell, they block the influx of calcium ions. giving an inhibitory effect.
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how do the different GABA receptors cause hyperpolarisation?
- GABA A receptor: influx of chloride ions
-GABA B: efflux of potassium ions (and also involves with blocking influx of calcium ions by interacting with calcium channels.
describe the cerebellum and its function?
- ‘little brain’ - prominent hindbrain structure, and accounts for approximetly 10% of the brains volume
- doesnt initiate movement, however detects differences in motor error between an intended movement and the actual movement, therefore aids the muscle cortex to produce precise and co-ordinated movement.
what are purkinje cells?
- purkinje cells are a class of GABAergic cells present in the cerebellum. These output to deep cerebellar neurones and causes generation of an error correction signal that can modify and cause precise movements
why is a balance of GABA and GLUTAMATE needed and how is it maintained?
-both of them work together to control the brains overall level of excitation
-the major excitatory neurotransmitter (glutamate) is comverted into the major inhibitory neurotransmitter (GABA)
what happens when the GABA-GLUTAMATE balance is not maintained and what is the treatment for this?
epilepsy: which is a brain disorder characterized by periodic and unpredictable seizures mediated by rhythmic firing of large groups of neurones.
- higher excitation-> increased inhibition.
-GABA A receptor enhancers, GAT blockers, GABA transaminase inhibitors, GAD modulators, produg
