Neurotransmitters Systems II: GABA & Glycine Flashcards
What are the criteria required for a molecule to be classed as a neurotransmitter?
The molecule must be synthesised and stored in the presynaptic neuron
The molecule must be released by the presynaptic axon terminal upon stimulation
The molecule must produce a response in the postsynaptic cell
What is the effect of inhibitory neurotransmitters?
Inhibitory neurotransmitters (e.g. GABA) can cause neuronal membrane hyperpolarisation - displacement of a membrane potential towards a more negative value
Explain the events that occur in a depolarisation
Resting potential -70mV
in a depolarisation event caused by Na+, membrane potential becomes more positive (~90mV) to trigger an action potential
What is hyperpolarisation?
Hyperpolarization involves the resting potential (-70mV) becoming more (hyper-) negative - action potential less likely to occur
What are the 2 mechanisms that cause hyperpolarisation?
2 main mechanisms cause hyperpolarisation:
- Influx of Cl-
- K+ efflux
Explain how Cl- influx causes hyperpolarisation
Negatively charged Cl- ions flow into the cell (facilitated by GABA)
How does K+ efflux lead to hyperpolarisation?
Moving positive K+ ions out of the cell causing the inside of the cell to become more negative
What is GABA?
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system (CNS)
Where is GABA most commonly known to induce its inhibitory effects?
GABA most commonly found as an inhibitory neurotransmitter in local circuit interneurons
How many synapses of the body does GABA have an effect on?
Approximately one third of synapses utilise GABA as their inhibitory neurotransmitter
How can we differentiate GABA and glutamate vesicles?
Glutamate is carried in round vesicles
GABA is transported in oval vesicles
Outline the synthesis of GABA
GABA synthesis from glutamate via Glutamate decarboxylase (GAD) enzyme action and a cofactor called Pyridoxal Phosphate (Vit. B6 derived)
=> OH group removed from glutamate to form GABA
Where is GABA synthesised?
Synthesised in the nerve terminals
How is GABA put in to vesicles?
Transported into vesicles by GABA transporters called vesicular inhibitory amino acid transporters (VIAAT)
Name the 2 major GABA receptors?
GABAa
GABAb
What type of receptor is GABAa?
The GABAₐ receptor is a ligand Gated Cl⁻ Channel
What happens when the GABAa receptor is stimulated?
When activated the channel opens allowing the movement of Cl- ions
=> causes hyperpolarisation
Explain how GABAa activation causes hyprpolarisation?
Resting potential (-70mV)
Cl- ions enter the cell when GABA binds to GABAₐ receptor
Causes hyperpolarisation - more negative membrane potential (-90mV)
Describe the structure of the GABAa receptor
The receptor is a pentameric structure:
Six 𝛂 subtypes (𝛂1-3)
Three ꞵ subtypes (ꞵ1-3) →
Three ɣ subtypes (ɣ1-3)
Also ε π ẟ θ subunits
2𝛂 and 2ꞵ ɣ most common configuration
How is GABAa activity regulated?
GABA activity terminated upon retake by GABA reuptake transporter GAT (EAAT for glutamate)
What are the different binding sites on the GABAa receptor?
Multiple binding sites on the GABAₐ receptor:
Agonists / antagonists e.g. GABA
Benzodiazepine binding site
Channel modulators e.g. GA, alcohol
Allosteric modulators e.g.
Barbiturates
Channel blockers e.g. Picrotoxin
Which part of the synaptic terminal are GABAa receptors found?
GABAₐ receptors are predominantly postsynaptic
Explain how GABA is transported across the synapse
- When GABA is released from its vesicles, it binds to its
GABAₐ receptor - GABA molecules then diffuse away once they’ve
activated their receptors
3, GABA is reuptaken into the presynaptic terminal
- Reuptake carried out by GAT
What kind of receptor is the GABAb receptor?
A metabotropic GPCR (similar to GLUT)