What do inhibitory neurotransmitters do?
They cause neuronal membrane hyperpolarisation (an action potential less likely to take place).
What is hyperpolarisation?
Displacement of a membrane potential towards a more negative value
What happens in a depolarisation?
At the resting potential, the membrane is -70mV. When there is sodium influx, the membrane potential becomes more positive - this is depolarisation.
What causes hyperpolarisation?
- Caused by the influx of negatively charged chloride ions in the cell.
- Potassium efflux causing positive ion out of the cell.
What is GABA?
Gamma-aminobutyric acid is the major inhibitory neurotransmitter in the CNS
How is GABA made?
It is synthesised from glutamate by the key enzyme glutamate decarboxylase (GAD), this requires a co-factor called pyridoxal phosphate derived from vitamin B6.
What is required for GAD to work?
Pyridoxal phosphate
Where does synthesis of GABA occur?
It occurs in the nerve terminals
What is the shape of glutamate and gaba vesicles and why is this important?
Glutamate is round
GABA is oval
To be able to distinguish them on a microscope image
How are GABA and Glycine transported into vesicles?
By vesicular inhibitory amino acid transporters
What type of channel is the GABAa receptor?
Ligand gated chloride channel
What is the structure of the GABAa receptor?
Six alpha subtypes (alpha 1 - alpha 6)
Three beta subtypes (Beta 1 - beta 3)
Three gamma subtypes (gamma 1 - gamma 3)
There is also other delta, zeta etc.
What is the most common structure of the GABAa receptor?
2alpha and 2 beta, gamma are the most common configuration
What activates GABAa receptors?
They are activated by GABA released from pre-synaptic neurons via synaptic vesicles
What causes the reuptake of GABA?
By the transporter called GABA reuptake transporter (GAT) which takes GABA back up into the pre-synaptic terminal. This will terminate GABA activity.
Where does GABA bind on the GABAa receptor?
Between the alpha and beta subunits
What else can bind to the GABAa receptor?
- Benzodiazepine binds between alpha and gamma subunits - used to treat anxiety and affects GABA neurotransmission
- Channel blockers e.g. Picrotoxin which prevents ion flow by blocking the channels
- Channel modulators e.g. GA (general anaesthetics)
- Allosteric modulators e.g. Barbiturates - also involved in anxiety treatment
What are GABAb receptors?
Metabotropic, G-coupled protein receptors
- Forms dimers which can be heteromers of GABAb1+2
- Coupled to a G protein - this is Gi/o.
- Activates potassium channels to facilitate potassium efflux which causes hyperpolarisation
- Block calcium influx into the cell to stop the chance of excitotoxicity
How is GABA reuptaken by neurons and glia?
Neurons and glial contain high-affinity Na+ dependent GABA re-uptake transporters (GAT).
Which GATs do neurons and glial cells have?
GAT-1 = neurons GAT-3 = glial cells
How is GABA degraded?
It is degraded by an enzyme called GABA transaminase (GABA-T). This forms succinic semialdehyde that is then degraded by an enzyme called succinic semialdehyde dehydrogenase (SSADH) into succinic acid.
What is the enzyme that degrades GABA into succinic semialdehyde?
GABA transaminase (GABA-T)
What is the enzyme that degrades succinic semialdehyde into succinic acid?
Succinic semialdehyde dehydrogenase (SSADH)
How are glutamate and GABA linked?
In one step, the major excitatory neurotransmitter, Glutamate is converted into the major inhibitory neurotransmitter, GABA. It is converted by glutamate decarboxylase (GAD) with the cofactor pyridoxal phosphate derived from vitamin B6.
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Introduction to Clinical Neuroscience52
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Structure of the Nervous System (Cranial Nerves)70
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Neurons and Glia66
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Glutamate57
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GABA and Glycine48
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Monoamines104
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Neurohormones89
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Vision82
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The Chemical Senses46
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Auditory and Vestibular Systems79
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Sleep53
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Somatosensation84
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Motivation61
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Learning and Memory60
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Control of Movement41
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Depression48
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Emotion35
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Anxiety41
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Schizophrenia31
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Language34
