Neuro 5 - Neurotransmitters + epilepsy tutorial

Question 1

What are the three classes of neurotransmitter?

Answer 1

Amino acids. Ex glutamate (most abundant in CNS, excitatory), GABA (inhibitory)
Amines - Noradrenaline, dopamine
Neuropeptides - opioid peptides e.g. endorphins

Question 2

Describe the process of synaptic transmission.

Answer 2

The vesicles dock on the pre-synaptic membrane and await a signal before the contents of the vesicles are expelled into the synaptic cleft.

Question 3

What allows the vesicles to dock stably?

Answer 3

Interaction between the vesicle membrane proteins and pre-synaptic membrane proteins.
–> these proteins have tails and can form super alpha helices between them

Question 4

What triggers the vesicle exocytosis?

Answer 4

There is a high concentration of calcium channels at the area where the vesicle docks. An influx of calcium causes vesicle exocytosis. They have calcium sensors located on vesicles.
(calcium increase is local)

Question 5

State three toxins that target vesicle proteins and the effects that they have.

Answer 5

Vesicular proteins are targets for neurotoxins
Tetanus - causes spastic paralysis (zinc dependent endopeptidase)
Botulinum - causes flacid paralysis
Alpha-latrotoxin - (black widow spider) prevents recycling of the vesicles and hence releases the transmitter to total depletion

Question 6

Describe a synaptic cycle

Answer 6

1. Early endosome
2. Neurotransmitter uptake
3. Reserve pool
4. Docking
5. Priming
6. Fusion after Ca2+ influx
7. Endocytosis
8. Recycling

Question 7

What does activation of transmitter release need?

Answer 7

• -> calcium dependent and requires rapid docking
• Transmitter containing vesicles to be docked on the presynaptic membrane
• Protein complex formation between vesicle, membrane and cytoplasmic proteins to enable both vesicle docking and a rapid response to Ca2+ entry leading to membrane fusion and exocytosis.
• ATP and vesicle recycling

Question 8

What are the two types of receptor and what is the most important difference in their properties?

Answer 8

Ion Channel Receptor - FAST - pentameric structure - GABA, glutamate - Entry of ion will affect polarization of cell, example Na+ entry by glutamate activation will depolarise.
G-protein linked receptor – SLOW - secondary messenger system - ACh at muscarinic receptors, DA, NA

Question 9

What is the effect of glutamate on the post-synaptic membrane?

Answer 9

Glutamate is excitatory - causes influx of Na+

Question 10

What is the effect of GABA on the post-synaptic membrane?

Answer 10

GABA is inhibitory - causes influx of Cl- so hyperpolarises

Question 11

What are the two main types of glutamate receptor? State some properties.

Answer 11

AMPA - rapid acting - responsible for the majority of fast excitatory synapses
NMDA - slower acting (despite still being excitatory and fast) - requires two conditions for activation = depolarisation of membrane + glutamate binding
NMDA lets in Na+ and Ca2+

Question 12

Where is glutamate formed?

Answer 12

Glutamate is a product of intermediary metabolism (e.g. glycolysis and TCA cycle)
Precursor alpha ketoglutarate

Question 13

Which transporter takes glutamate up into glial cells on the pre-synaptic membrane?

Answer 13

Excitatory Amino Acid Transporter 2 (EAAT 2)

Question 14

How is glutamate inactivated in the glial cells?

Answer 14

Glutamate is converted to glutamine by GLUTAMINE SYNTHETASE

Question 15

What causes epilepsy?

Answer 15

Increased release of glutamate causing hyperexcitability

Question 16

Describe the structure of GABA and state how it is produced.

Answer 16

GABA has the same structure as Glutamate but with the carboxyl group removed. So GABA is produced from glutamate by the action of GLUTAMIC ACID DECARBOXYLASE (GAD).

Question 17

What transporter takes GABA up into the glial cells?

Answer 17

GABA transporters (GAT) on presynaptic membrane and glial cells

Question 18

Describe the inactivation of GABA in the glial cells.

Answer 18

Processing: GABA enters GAT –> GABA Transaminase (GABA T) makes GABA -> succinate semi-aldehyde (SSA) (later -> succinate for TCA = GABA shunt)

Question 19

Describe how the GABA receptor can be manipulated to create treatments for epilepsy.

Answer 19

Drugs facilitate GABA transmission as GABA is inhibiting
Also inhibit GABA T so that GABA is not taken up into cells, stays in synapse to have more effect (cannot be inactivated as this is the role of GABA T)

Question 20

How are different epilepsies classfied?

Answer 20

Generalised or partial

Generalised:

• tonic-clonic
• absence
• myoclonic
• atonic

Partial:

• simple
• complex
• scondarily generalized

Question 21

Where does benzodiazepines act?

Answer 21

On the GABA receptor