Neurotransmission and Pharmacology

Question 1

What does information transfer across a synapse require?

Answer 1

Release of neurotransmitter
Interaction of neurotransmitter with postsynaptic receptors

Question 2

What 3 processes are neurones adapted to do?

Answer 2

Information reception
Integration
Rapid transfer (AP)

Question 3

What does communication between cells require?

Answer 3

Neurotransmitter release

Question 4

Describe the structure of a neurone.

Answer 4

Spines
Dendrites
Soma
Axon
Synaptic terminal

Question 5

How many synapses do each neurone make?

Answer 5

several hundred or thousands

Question 6

Where is neurotransmission restricted to?

Answer 6

the synapses (they are specialized structures)

Question 7

How big is the gap of a synapse?

Answer 7

roughly 20-100nm

Question 8

What are the 3 stages of synaptic transmission?

Answer 8

1. biosynthesis, packaging and release of neurotransmitter
2. receptor action
3. inactivation

Question 9

How do transmitters vary?

Answer 9

Enormous diversity in variety of transmitters and their receptors including Amino acids (e.g. glutamate, γ-aminobutyric acid [GABA], glycine [Gly]), Amines (e.g. noradrenaline [NA] and dopamine [DA]) and Neuropeptides (e.g. opioid peptides)

Vary in abundance from nM to mM CNS tissue concentrations

May mediate rapid (micros- ms) or slower effects (secs)

Question 10

What are the essential features of synaptic transmission?

Answer 10

Restricted to specialised structures - the synapses

Calcium is essential - transmitter release requires an increase in intracellular Ca2+ (200 microM)

Transmission is fast - within ms

Synaptic vesicles (SVs) provide the source of neurotransmitter (4,000-10,000 molecules per SV)

Question 11

What is transmitter release dependent on?

Answer 11

calcium dependent
and requires RAPID transduction

Question 12

Describe the process of neurotransmitter release.

Answer 12

Membrane depolarisation-> Ca2+ channels open-> Ca2+ influx-> Vesicle fusion-> vesicle exocytosis-> transmitter release

Question 13

What are the stages of the neurotransmitter vesicle in the pre-synaptic neurone?

Answer 13

Budding-> forms endosome->?
Budding->
Docking->
Priming->
Fusion->
Neurotransmitter release

Question 14

How do rapid release rates occur?

Answer 14

Synaptic vesicles are filled with neurotransmitter (T) and docked in the synaptic zone
Special proteins on the vesicle and presynaptic membrane enable fusion & exocytosis

Question 15

What is an example of a target for neurotoxins?

Answer 15

vesicular proteins

Question 16

Give 2 examples of neurotoxins affecting vesicles and how they work?

Answer 16

Alpha latrotoxin (from spider)
- lots of stimulation
- promotes Ca2+ influx
- excess sweating
- too much neurotransmitter
- constant spasm

Botulinum toxin (C botulinum)
- most potent toxin in the world
- prevent neurotransmitter release= paralysis of skeletal muscle

Question 17

What are the transmitter release requirements?

Answer 17

1. Calcium-dependent (Ca2+)
2. Transmitter-containing vesicles to be docked on the presynaptic membrane
3. 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 18

What is neurotransmitter action defined by?

Answer 18

receptor kinetics

Question 19

What is the difference between ion channel-linked receptor and G-protein-coupled receptors?

Answer 19

Question 20

Give examples of ion channel linked receptors and g-protein-coupled receptors.

Answer 20

Question 21

Describe ion-channel linked receptors.

Answer 21

Question 22

What causes excitatory postsynaptic potential?

Answer 22

Na+ entering the cell

Question 23

What causes inhibitory postsynaptic potential?

Answer 23

Cl- entering the cell

Question 24

What are the type of glutamate receptors?

Answer 24

AMPA and NMDA

Question 25

Describe AMPA and NMDA receptors?

Answer 25

Question 26

What happens in an excitatory Glu synapse?

Answer 26

Question 27

What happens in an inhibitory GABA synapse?

Answer 27

Question 28

What leads to seizures?

Answer 28

Abnormal cell firing leads to seizures associated with excess GLUTAMATE in the synapse
?Aetiology uncertain – Glutamine synthetase?

Question 29

What is an EEG?

Answer 29

Electroencephalography (EEG) measures electrical activity in the brain

Question 30

What converts glutamate to something else?

Answer 30

Glutamine synthetase to glutamine in glial cells

Question 31

What is epilepsy?

Answer 31

One of the common neurological conditions affecting 50 million people worldwide

Characterised by recurrent seizures due to abnormal neuronal excitability

Despite advances in modulating seizure generation and propagation the disease can be disabling

25-30% don’t respond to treatment

Question 32

What are symptoms of epilepsy?

Answer 32

Loss of consciousness
Weakness
Anxiety
Staring
Contracting and jerking of muscles
Confused speech

Question 33

What is a possible treatment for epilepsy?

Answer 33

The synaptic properties of GABA may be modulated pharmacologically as an approach to treating epilepsy

Question 34

How do you monitor seizures?

Answer 34

With EEG (electroencephalography)
excessive activation in the brain, associated with excess glutamate