Lecture 10: Neuromuscular Junction

Question 1

How do action potentials open Ca2+ channels?

Answer 1

Depolarization opens voltage-gated Ca2+ channels

Question 2

What are the 5 steps leading to transmitter release?

Answer 2

1. Ca2+ entry through Ca2+ channels
2. Ca2+ binds to synaptotagmin
3. Vesicle brought close to membrane
4. Snare complex makes a fusion pore
5. Transmitter released through pore

Question 3

How does activation of nicotine Ach receptors lead to an action potential in skeletal muscle?

Answer 3

Ach binds to nicotinic Ach receptors on muscle end-plate, causing them to open and the flow of Na+ causes a depolarization (end-plate potential), which depolarizes the adjacent muscle membrane and activates voltage-gated Na+ channels, initiating an action potential in the muscle fibers

Question 4

What are the 2 main types of blockers of nicotinic Ach receptors?

Answer 4

Competitive blocker and depolarizing blocker

Question 5

How do competitive blockers work?

Answer 5

d-tubocurarine sits at site where Ach normally binds, preventing the ion channel from opening, no neurotransmitter release = no depolarizing

Question 6

How do depolarizing blockers work?

Answer 6

Succinylcholine act as Ach receptor agonists, but cannot be degraded by Ach esterase, so remains bound to Na+ channels, Na+ continues to flow in, there is a maintained depolarization which fails to activate adjacent Na+ channels as they have become inactivated

Question 7

Why does myasthenia gravis cause weakness?

Answer 7

Antibodies directed against nAchR on postsynaptic membrane of skeletal muscle, leading to a loss of functional nAchR, end plate potential amplitude reduced, unlikely to reach threshold, muscle contraction decrease