Neuro: Neurotransmitters Systems II: GABA & Glycine Flashcards
What type of neurotransmitter are GABA and glycine?
Inhibitory neurotransmitters - cause membrane potential hyperpolarisation
What is hyperpolarisation?
Displacement of a membrane potential towards a more negative value
What are the two ways that hyperpolarisation of a membrane can occur?
- Influx of negatively charged ions into the cell e.g. Cl-
- Efflux of K+ ions out of the cell
How is GABA synthesised within the pre-synaptic neurone?
- GABA is produced from glutamate via the enzyme glutamate decarboxylase (GAD)
- Glutamate decarboxylase requires a cofactor called pyridoxal phosphate
How is GABA stored within the pre-synaptic neurone once it’s synthesised?
GABA is transported into synaptic vesicles via the vesicular inhibitory amino acid transporter (VIAAT)
What is the difference in the synaptic vesicles that GABA and glutamate are stored in?
- Glutamate stored in round synaptic vesicles
- GABA stored in oval synaptic vesicles
What are the different types of GABA receptor?
- GABAA receptor
- GABAB receptor
What type of receptor is the GABAA receptor and how does it cause hyperpolarisation?
- GABAA receptor is a ligand-gated Cl- channel
- It causes hyperpolarisation by causing the influx of Cl- into the cell when activated
What are the different subunits/subtypes that can make up the GABAA receptor?
- α1-α6
- β1-β3
- γ1-γ3
What is the most common configuration of subunits of the GABAA receptor?
- Pentameric structure
- 2α 2β γ most common configuration
What is the name of the transporter responsible for the re-uptake of GABA back into the pre-synaptic neurone?
GABA reuptake transporter (GAT)
What are the different binding sites present on the GABAA receptor?
- GABA binding sites - between α and β subunits
- Benzodiazepine binding site
- Channel blocker binding sites
- Channel modulator binding sites
- Allosteric modulator binding sites
What type of receptor is the GABAB receptor?
G-protein coupled receptor
What are the different subunits of the GABAB receptor?
- GABAB1
- GABAB2
What are the different configurations of the subunits of GABAB receptors?
- Form dimers
- Can be homomers - e.g. GABAB1 and GABAB1
- Can heteromers - e.g. GABAB1 and GABAB2
What type of G protein is the GABAB receptor coupled to?
Gi/o
How does activation of the GABAB receptor cause hyperpolarisation?
- Activation of GABAB receptor results in K+ efflux out of the cell
- Also causes inactivation of the voltage-gated Ca2+ channel preventing Ca2+ influx into the cell
Both neurons and glial cells have GABA reuptake transporters (GAT), what type of GAT do the glial cells and neurons have?
- Glial cells have GAT-3
- Neurons have GAT-1
Explain how is GABA degraded
- GABA is converted into Succinic semialdehyde by GABA transaminase (GABA-T)
- Succinic semialdehyde is then converted into succinic acid by Succinic semialdehyde dehydrogenase (SSADH)
How is the brain able to control it’s level of excitation?
Brain is able to convert Glutamate into GABA via Glutamate decarboxylase (and pyridoxal phosphate) to keep a constant excitatory-inhibitory balance
What is epilepsy?
Brain disorder characterised by periodic and unpredictable seizures mediated by the rhythmic firing of large groups of neurons
What are the different types drugs that can treat epilepsy via increasing inhibition via GABA?
- GABAA receptor enhancers e.g. progesterone
- GABA reuptake transporter (GAT) blockers
- GABA-transaminase inhibitors
- Glutamate decarboxylase (GAD) modulators
- Progabide - precusor to GABA
What is anxiety?
Feeling of unease which can range from mild to severe
What are anxiolytics and what receptor do they work on?
- Anxiolytics are drugs used to reduce anxiety
- They bind to/work on the GABAA receptor
