5.2 Synaptic Transmission And The Neuromuscular Junction

Question 1

List the stages of an AP passing from nerve to muscle (neuromuscular junction)

Answer 1

1. AP comes down axon to NM junction
2. Ca2+ channels open, influx
3. Ca2+ binds to synaptotagmin (role is to bring vesicle full of NT close to membrane)
4. Vesicle full of NT brought close to membrane
5. Vesicles interact with snare complex to form a fusion pore
6. Realease of NT ACh into synaptic cleft
7. Diffuses across cleft, binds to nicotinic ACh receptor on end plate causing conformational change
8. Causes pore to open, Na+ in, K+ out, then Na+ in
9. (End plate potential) Depolarisation - will try to reach reversal potential for this channel (pt at which no net flow of charge when channel open) roughly between Ena and Ek
10. AChesterase degrades ACh

Question 2

How can higher levels of NT be released?

Answer 2

Size of AP cannot increase, however frequency can by increases Ca2+ conc leading to more NT release

Question 3

Describe Ca2+ voltage gated channels

Answer 3

4 subunits
Voltage sensing domain
L-type - target of many drugs and can be blocked
As stopped release of Ca =less response

Question 4

Differences between Ca2+ and Na+ channels

Answer 4

Ca+ channels open at slightly more positive potentials than Na+
channels activate and inactivate slower than Na+ channels

Question 5

What is inactivation of Ca2+ channels dependent upon?

Answer 5

Ca2+ inside the cell

Question 6

What are the 2 ways to block an nACh receptor?

Answer 6

Nicotinic ACh receptor

1. Competitive blocker (d-tubocurarine (paralysis))
   - binds and blocks
   - no conformational change so ACh cannot activate channel, but you can inc conc of ACh to overcome it
   - response of ACh diminished
2. Depolarising blocker (succinylcholine)
   - binds to nACh and depolarises
   - so you get muscle contractions but then stops as maintained depolarisation
   - have to hyperpolarise to become activated again
   - short acting muscle relaxant and local anaesthetic

Question 7

Give a clinical example where an action potential cannot occur

Answer 7

Myasthenia graves

• autoimmune disease targeting nAChR
• antibodies against nAChR on post synaptic membrane of skeletal muscle
• so loss of function of these receptors is by complement mediated lysis and receptor degradation
• end plate potentials reduced in amplitude leading to muscle weakness
• Suffer profound weakness - cant walk

Question 8

Difference between nAChR and mAChR?

Answer 8

mAChR - parasympathetic branch of ANS, slower response as coupled with GPCRs and trigger cascade of events in cells
nAChR - fast depolarisation as ligand gated ion channel