What is a neurotransmitter?
A chemical substance released at the end of a nerve fibre by the arrival of a nerve impulse to another nerve fibre, muscle fibre or some other structure
What is an excitatory neurotransmitter?
Increases the probability that the target cell will fire an action potential
Give an example of an excitatory neurotransmitter:
What is an inhibitory neurotransmitter?
Decreases the probability that the target cell will fire and action potential
Give two examples of inhibitory neurotransmitters:
GABA (fast, found in virtually every part of the brain = short interneurones e.g. pain modulation)
Glycine (the inhibitory transmitter in the spinal cord)
Anxiety is a disorder of the...
Too few GABA = Anxiety
What was GABA first discovered as?
A product of microbial and plant metabolism
Which drug enhances the effects of GABA?
What causes epilepsy?
When GABA is lacking in certain parts of the brain
Where are there long GABAergic tracts to?
Which enzyme produces GABA?
Glutamic Acid Decarboxylase (GAD) -> found primarily in CNS
Co-enzyme = Vitamin B6
Which reaction produces GABA?
Glutamate -> GABA + CO2
How many isoforms of Glutamic Acid Decarboxylase are found in the brain?
(GAD1 & GAD2 -> evolved separately but do same job!)
What is a glial cell?
A helper axillary cell = mop up and release neurotransmitter
What breaks GABA down?
Co-factor = Vitamin B6= located in the mitochondria
What does GABA-T break GABA down into?
Which drug is the most potent inhibitor of GABA-T?
Gabaculine (used more in lab than clinically)
What happens inside the cell after Gabaculine is given?
- Lots of GABA in cleft
- Eventually it stops vesicles containing GABA (relies on action of GAD to package produce GABA from glutamate and package into vesicle) = action potential = no release of GABA = no inhibition = Anxiety
Which cells express GABA receptors?
- Most neurones in the CNS
- Glial cells (astrocytes) = ANS neurones
When GABA binds what happens to the neurone?
Shift in membrane permeability to Chloride ions
postsynaptic inhibition = hyperpolarisation
presynaptic inhibition = depolarisation
How many types of GABA receptor are there?
What are they called?
GABA-A & GABA-B
What type of receptor is GABA-A?
Ligand-gated ion (chloride) channel
What type of receptor is GABA-B?
Which drug does GABA enhance the binding of?
Why does GABA enhance binding of benzodiazepine?
GABA-A and Benzodiazepine (BDZ) receptor make up 2 separate parts of the same complex
Which is the most prevalent GABA receptor?
How many subunits does the GABA-A receptor have?
N.b. subunit composition varies between brain regions and neuronal subpopulations (how we get sensitivity to specific regions)
Between which two subunits on the GABA-A receptor do benzodiazepines bind?
Alpha & Gamma
Which subunit of the GABA-A receptor binds GABA?
Whats the birds eye view subunit arrangement for the GABA-A receptor?