Lecture 4: Neurotransmitters and Pharmacology

Question 1

What does information transfer across the synapse require?

Answer 1

Release of neurotransmitters and interaction with postsynaptic receptors

Question 2

What are key features of synaptic transmission?

Answer 2

• rapid timescale
• diversity
• adaptability
• plasticity
• learning and memory

Question 3

What do the spines on dendrites do?

Answer 3

Increase surface area for more synaptic connections

Question 4

How does the way the information is being transferred change?

Answer 4

The transmission is electrical in the pre-synaptic neurone before becoming chemical neurotransmission when it passes across the synapse and then it returns to electrical transmission in the post-synaptic neurone

Question 5

What are the 3 stages of synaptic transmission?

Answer 5

1. Biosynthesis, packaging and release of neurotransmitter
2. Receptor action
3. Inactivation

Question 6

What can neurotransmitters be?

Answer 6

• amino acids (e.g. glutamate, GABA)
• amines (noradrenaline, dopamine)
• neuropeptides (e.g. opioid peptides)

Question 7

What is the most important excitatory neurotransmitter?

Answer 7

glutamate

Question 8

What is the most important inhibitory neurotransmitter?

Answer 8

GABA

Question 9

Which inhibitory neurotransmitter is present in the spinal cord?

Answer 9

glycine

Question 10

What is considered a rapid effect or slower effect?

Answer 10

Rapid = us - ms
slower = secs

Question 11

What does neurotransmitter release rely on?

Answer 11

increase in intracellular Ca2+ (200um) - this occurs by opening of Ca2+ ion channels

Question 12

What in the presynaptic neurone provides the source of neurotransmitter?

Answer 12

synaptic vesicles

Question 13

Outline the steps that lead to neurotransmitter release.

Answer 13

1. membrane depolarisation
2. Ca2+ channels open
3. Ca2+ influx
4. Vesicle fusion
5. Vesicle exocytosis
6. Transmitter release

Question 14

What is the process called from the Ca2+ channels opening to transmitter release?

Answer 14

Electrochemical transduction

Question 15

What are the synaptic vesicles?

Answer 15

Vesicles docked in the synaptic zone filled with neurotransmitter

Question 16

What are the proteins on synaptic vesicles called and what are they important for?

Answer 16

Vesicular proteins - important in docking/fusion process and exocytosis

Question 17

What are vesicular proteins the target of?

Answer 17

Neurotoxins

Question 18

What do Zn2+ endopeptidases inhibit?

Answer 18

transmitter release

Question 19

What does Tetanus toxin C tetani cause?

Answer 19

paralysis (breaks down skeletal muscle)

Question 20

What does botulinum toxin C botulinum cause?

Answer 20

flaccid paralysis (muscles lose functionality)

Question 21

What does alpha latrotoxin (from black widow spider) do?

Answer 21

Stimulates ACh release and cholinergic transmission to depletion

Question 22

Outline transmitter release requirements.

Answer 22

• calcium dependent
• transmitter-containing vesicles to be docked on 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 (lots of mitochondria)

Question 23

How is neurotransmitter action defined?

Answer 23

By receptor kinetics

Question 24

What 2 receptors could a neurotransmitter bind to?

Answer 24

• ion channel receptor

- G protein coupled receptor

Question 25

What do ion channel receptors mediate?

Answer 25

- Fast response (msecs) | - mediate all fast excitatory and inhibitory transmission

Question 26

What do G-protein coupled receptors mediate?

Answer 26

- slow response (secs/mins) | - effectors may be enzymes (adenyl cyclase, phospholipase C or channels e.g. Ca2+, K+)

Question 27

What are some examples of ion channel receptors?

Answer 27

``` CNS: glutamate, GABA Neuromuscular junction (NMJ): ACh at nicotinic receptors ```

Question 28

What are some examples of G-protein coupled receptors?

Answer 28

CNS and PNS: ACh at muscarinic receptors, dopamine (DA), noradrenaline (NA), serotonin (5HT) and neuropeptides (e.g. enkephalin)

Question 29

What are ion channel-linked receptors?

Answer 29

multiple subunit combinations-distinct functional properties

Question 30

What are some types of ion channel-linked receptors?

Answer 30

- nicotinic cholinergic receptors (nAChR) - glutamate (GluR) - GABA (GABAR) - Glycine (GlyR) receptors

Question 31

What ion causes hyperpolarisation?

Answer 31

Cl- (makes resting potential even more negative so it's harder to activate/propagate an action potential)

Question 32

What is an EPSP?

Answer 32

excitatory postsynaptic potential (excitatory neurotransmitter receptor)

Question 33

What is an IPSP?

Answer 33

inhibitory postsynaptic potential (inhibitory neurotransmitter receptor)

Question 34

What are the 2 different glutamate receptors?

Answer 34

- AMPA receptor | - NMDA receptor

Question 35

What is the AMPA receptor for?

Answer 35

- majority of fast excitatory synapses - rapid onset, offset and desensitisation - Na+ influx

Question 36

What is the NMDA receptor for?

Answer 36

- slow component of excitatory transmission - serve as coincidence detectors which underlie learning mechanisms - Ca2+/Na+

Question 37

Outline what occurs at an excitatory CNS synapse.

Answer 37

1) glutamate synthesised from glucose via TCA cycle and transamination 2) Glutamate reversibly binds post-synaptic receptors (linked to ion channels) 3) Rapid uptake of glutamate by excitatory amino acid transporters (EAATs) 4) Glutamate enzymatically modified by glutamine synthetase to glutamine in glial cell

Question 38

What can lead to seizures?

Answer 38

abnormal cell firing with excess glutamate in the synapse

Question 39

How can you measure electrical activity in the brain?

Answer 39

Electroencephalography

Question 40

What is epilepsy characterised by?

Answer 40

recurrent seizures due to abnormal neuronal excitability

Question 41

Outline what occurs at an inhibitory CNS synapse.

Answer 41

1. GABA formed by decarboxylation of glutamate by glutamic acid decarboxylase (GAD) 2. GABA reversibly binds post-synaptic receptors (Linked to ion channels) 3. rapid uptake of GABA transporters (GATs) 4. GABA enzymatically modified by GABA-transaminase to succinate semialdehyde in glial cell

Question 42

Which drugs facilitate GABA transmission?

Answer 42

- antiepileptic - anxiolytic - sedative - muscle relaxant