Neurotransmitter Systems II: GABA And Glycine Flashcards
What does GABA stand for?
Gamma-aminobutyric acid
What is GABA?
Major inhibitory neurotransmitter in the CNS
What is the main precursor to GABA?
Glucose
How does glucose turn into GABA?
Glucose -> glutamate, which then is turned into GABA by glutamate decarboxylase with the cofactor pyridoxal phosphatase
What shaped vesicles is glutamate stored in?
Round
What shaped vesicles is GABA stored in
Oval
How is GABA retaken up?
High affinity sodium dependant GABA transporters GAT-1 on neurons and GAT-3 on glial cells
What are the steps in GABA degredation (no enzymes)?
GABA -> succinic semialdehyde -> succinic acid
What enzyme catalyses GABA -> succinic semialdehyde?
GABA Transaminase (GABA-T)
What enzyme catalyses succinic semialdehyde -> succinic acid?
Succinic semialdehyde dehydrogenase (SSADH)
What type of receptors are GABAa receptors?
Ionotropic
What type of receptors are GABAb receptors?
Metabotropic
What happens upon GABA binding to GABAa receptor?
Channel opens and allows the influx of chloride ions
What are the possible GABAa receptor subunits?
6 alpha, 3 beta, 3 gamma, delta, epsilon, pi and theta
What is the most common GABAa configuration?
2 alpha, 2 beta and a gamma
Why are GABAa receptors a key drug target?
Multiple binding sites
Where do agonists/ antagonists bind on GABAa receptors?
Between the alpha and beta subunits
Where does benzodiazepine bind on GABAa receptors?
Between alpha and gamma subunits
Where do channel blockers bind on GABAa receptors?
Blocks the ion pore (non-competitive antagonist)
How do channel modulators work on GABAa receptors?
Increase the opening
What is an example of a GABAa channel blocker?
Picrotoxin
Where do allosteric modulators bind on GABAa receptors?
The receptor
Give an example of a GABAa allosteric modulator
Barbituates
What are the heteromers of the GABAb receptor?
GABAb1 and GABAb2
How does the GABAb receptor work?
Binding stimulates the Gi/O pathway
What does activation of the Gi/O pathway cause?
Activates adenylyl cyclase to reduce cAMP levels, which activates potassium channels, causing an effluent
What are the two ways in which hyperpolarisation can happen?
Influx of calcium or efflux of potassium
How much of the brains volume does the cerebellum account for?
10%
What is the function of the cerebellum?
Helps the motor cortex to procure precise and coordinated movements- detects the differences in motor error between an intended movement and the actual movement
What are purkinje cells?
A class of GABAergic neurons that comprise the principle projection neurons of the cerebellar cortex
What do the purkinje cells dendritic trees receive?
Convergent input from cells in the molecular layer
What do the purkinje cells dendritic trees send out?
GABAergic projections to Deep cerebellar neurons
What does the GABAergic projection to the deep cerebellar neurons generate?
An error connection signal that can modify movements
What do GABA projections in the cerebellum provide the basis for?
Real time control of precise and synchronous movement
What two things work together to control the brains overall level of excitation?
GABA and glutamate
What is epilepsy?
Brain disorder characterised by periodic and unpredictable seizures mediated by the rhythmic firing of large groups of neurons
How do epilepsy drugs work?
Increase inhibition by increasing GABA
What is glycine?
Major inhibitory neurotransmitter in the CNS
Where is glycine most commonly found?
In the ventral ramus Which is the location for spinal interneuron terminals
What is the precursor to glycine?
Serine
What catalyses serine -> glycine?
Serine hydroxymethyltransferase
Where is glycine synthesised?
Nerve terminals
What class of enzymes causes the reuptake of glycine?
GlyT 1 and 2
What enzyme is glycine -> serine catalysed by?
Serine hydroxymethyl
What type of receptor does glycine bind to?
Ligand gated ion channel
What happens when glycine binds to its receptor?
Allows chloride ions into the neuron, leading to hyperpolarisation
What different subtypes of the glycine receptor are there?
4 alpha, one beta
What are the most common glycine LGIC configurations?
3 alpha, 2 beta or 4 alpha, 1 beta
What potently blocks glycine receptors?
Plant alkaloid strychnine
What is hyperekplexia?
A rare disorder characterised by hypertonic and increased muscle tone
What can hyperekplexia lead to?
Neuronal hyperexcitability and hypertonic and an exaggerated startle response
Why do the fainting goats faint?
Decreased muscle chloride conductance, which can be caused by glycine receptor mutations
