Neurotransmitters (4)

Question 1

What is synaptic transmission?

Answer 1

information transfer across the synapse- requires release of neurotransmitters and their interaction with postsynaptic receptors

Question 2

What are the 3 stages of synaptic transmission?

Answer 2

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

Question 3

How is a CNS synapse activated?

Answer 3

• arrival of AP down axon at nerve terminal–> depolarised
• rapid Na+ influx and K+ flow out–> AP causes opening of voltage sensitive Ca2+ channels
• Ca2+ flows into presynaptic terminal down conc. gradient (higher outside)
• stimulates exocytotic release of NT–> diffuses across synaptic cleft and contacts postsynaptic receptors
• excitation or inhibition
• NT reuptaken back into presynaptic terminal + reloaded into vesicles
• activation of Na+/K+ pump equilibrates ionic concentrations back to resting potential

Question 4

What happens in neurotransmitter release?

Answer 4

empty vesicle filled w/ NT by protein pumps on surface

• -> proteins incorporated on surface (important in docking)
• ->influx of calcium allows vesicles to dock on presynaptic membrane
• -> vesicles primed
• -> further calcium influx results in fusion of vesicles w/ presynaptic membrane, opening of vesicles and rapid release of NT into synaptic cleft

Question 5

How does alpha latrotoxin (from black widow spider) have a lethal effect?

Answer 5

stimulates an explosive ACh release from terminals, so they become depleted–> transmission fails–> if to respiratory muscles, causes respiratory arrest

Question 6

How do zinc dependent endopeptidases act as neurotoxins?

Answer 6

e.g. Tetanus toxin
inhibits release of NT
causes paralysis

Question 7

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

Answer 7

ion channel receptors (ionotropic) and G-protein coupled receptors

Question 8

What are the differences between ion channel and G-protein coupled receptors?

Answer 8

ion channel –> FAST responses–> mediate all fast excitatory+inhibitory transmission

G-protein coupled–> SLOW responses–> have 7 transmembrane segments in lipid bilayer–> effectors: enzymes or channels (need to pickup their G protein so slower)

Question 9

What are some examples of NT that act on ion channel receptors?

Answer 9

CNS: glutamate (excitatory), GABA (inhibitory)

NMJ in PNS: ACh at nicotinic receptors

Question 10

What are some examples of NT that act on G-protein couple receptors?

Answer 10

CNS and PNS: ACh at muscarinic receptors, dopamine, noradrenaline, serotonin and neuropeptides

Question 11

What are AMPA receptors?

Answer 11

glutamate receptors

• linked to sodium channels
• fast, excitatory
• rapid onset, onset and desensitisation

Question 12

What are NMDA receptors?

Answer 12

glutamate receptors

• allow both calcium AND sodium influx
• slower component of excitatory transmission
• ‘coincidence detectors’ (can’t be activated alone, need to be depolarised first) learning and memory

Question 13

What happens at an excitatory CNS synapse?

Answer 13

1. glutamate synthesised from glucose and packaged into vesicles
2. glutamate released by influx of Ca2+ etc..
3. glutamate reversibly binds to post-synaptic receptors (AMPA and NMDA)
4. glutamate inactivated by uptake into surrounding glial cells (glutamine synthesise converts it to glutamine) and into presynaptic terminal

Question 14

How can we explain seizures?

Answer 14

• too much synaptic glutamate in CNS–> generates AP firing–> inc. EEG activity
• after glutamate levels come down, inc. glutamine levels
• inc. in glutamate activity would normally stimulate GABA neurons