Week 1- Neurotransmitters and Pharmacology

Question 1

What is synaptic transmission?

Answer 1

The release of neurotransmitters and their interaction with postsynaptic receptors

Question 2

Describe the movement of signals down a neuron

Answer 2

1. Information reception
2. Integration of signal
3. Rapid transmission

Question 3

What type of transmission occurs in a synapse?

Answer 3

Chemical

Question 4

How large is a synaptic cleft?

Answer 4

20-100nm

Question 5

What are the 3 stages of synaptic transmission?

Answer 5

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

Question 6

What are some examples of neurotransmitters?

Answer 6

Amino acids, amines and neuropeptides

Question 7

Describe the activation of a CNS synapse

Answer 7

1. AP arrives and causes depolarisation
2. Na+ influx
3. K+ efflux
4. Ca 2+ influx
5. Exocytotic release of transmitter
6. Transmitter has contact w post synaptic receptors
7. Excitatory receptors causes Na+ influx triggering AP
8. Once over, Na/K pump retains ionic balance

Question 8

How much intracellular Ca 2+ is required?

Answer 8

200 micro m

Question 9

How fast is transmission?

Answer 9

Very quick, within milliseconds

Question 10

What is electromechanical transduction?

Answer 10

Ca2+ influx, vesicle fusion, vesicle exocytosis, transmitter release

Question 11

How does neurotransmitter exocytosis work?

Answer 11

1. Vesicles are pumped with transmitter
2. Vesicles dock on presynaptic membrane (needs protein complex formation between vesicle, membrane and cytoplasmic proteins)
3. Vesicles are primed
4. Further Ca2+ influx causes fusion of vesicles w membrane
5. Neurotransmitter is released
6. Vesicles are pinched off via endocytosis and recycled
   NOTE: vesicular proteins help with docking

Question 12

What do neurotoxins target?

Answer 12

Vesicular proteins

Question 13

Whats does neurotoxin alpha latrotoxin do?

Answer 13

Stimulates transmitter release to depletion

Question 14

Whats does neurotoxin Zn 2+ dependant endopeptidases do?

Answer 14

Inhibit transmitter release

Question 15

Whats does neurotoxin tetanus toxin C tetani do?

Answer 15

Causes paralysis

Question 16

Whats does neurotoxin C botulinum do?

Answer 16

Cause flaccid paralysis

Question 17

What are the 2 main classes of receptors that transmitters work on?

Answer 17

Ion channel receptors (fast excitatory and inhibitory responses i.e. milliseconds) and G protein coupled receptors (slow responses i.e. secs/mins, effectors may be enzymes or channels)

Question 18

Describe ion channel receptors

Answer 18

They have multiple subunits which can be rearranged to give slightly different receptors with different functional properties

Question 19

Describe the different between excitatory and inhibitory neurotransmitter receptors

Answer 19

Excitatory: membrane potential increases
Inhibitory: membrane potential decreases, reducing chances of going over threshold and generating APs

Question 20

What are the 2 main glutamate receptors?

Answer 20

AMPA (fast excitatory synapses with rapid onset and offset, only allows sodium in) and NMDA (slow component of excitatory transmission, allow calcium and sodium in)

Question 21

Describe the process occurring at an excitatory synapse

Answer 21

1. Glutamate is synthesized from vous ose via TCA cycle and transamination
2. Glutamate irreversibly binds post synaptic NMDA receptors (linked to ion channels)
3. Rapid reuptake of glutamate by glial cells and presynaptically into nerve terminal where it can be reused
4. Glutamate in glial cells is modified by glutamine synthetase to glutamine

Question 22

What happens if there is an excessive amount of glutamate in synapses?

Answer 22

Usually GABA neurons bring excitation back down to a normal level after which there should be an increase in glutamine levels, if GABA fails to do so there is increased EEG activity which can increase seizures.

Question 23

What is epilepsy?

Answer 23

Reccurent seizures due to abnormal neuronal excitability

Question 24

Describe the GABA CNS synapse

Answer 24

1. GABA formed by decarboxylation of glutamate by glutamic acid decarboxylase
2. GABA reversible binds to post synaptic receptors
3. Rapid reuptake of GABA by GABA transporters (GATs) into glial cells and presynaptic terminals
4. In glial cells and presynaptic terminal GABA is converted to succinate semialdehyde by GABA transaminase

Question 25

What is the structure of GABA receptor?

Answer 25

Has 5 subunits, drugs like benzodiazepines they enhance the receptor function.