L10: Skeletal Muscle Neurophysiology 2

Question 1

What causes Ca2+ to be released?

Answer 1

AP in axon opens v. gated Ca2+ channels

Question 2

What does Ca2+ release trigger?

Answer 2

Ca2+ triggers vesicle fusion, release of Ach at the active site → diffuses across the synaptic cleft

Question 3

What does ACh bind to?

Answer 3

Ach binds nAchR on muscle fiber

Question 4

What happens in the post-synaptic cell?

Answer 4

nAchR channel opens, Na+ enters –> local depolarisation spreads to extra-junctional membrane

Question 5

How is the signal terminated?

Answer 5

When ACh degraded by AChE

Question 6

What happens to ACh during prolonged contraction?

Answer 6

ACh reserve is slowly used up during prolonged contraction because regeneration of ACh is takes a bit of time

Question 7

Describe redundancy in terms of the NMJ

Answer 7

Lots of ACh in reserve, lots of receptors = efficient system, has some redundancy so can achieve full response without all receptors bound

Question 8

Describe the structure of nAChR and its subunits

Answer 8

• Five subunits, each with 4x transmembrane domains
• Anchored in the membrane, subunits together
• Has a central pocket surrounded by subunits, has no membrane or anything hydrophobic in it = pore

Question 9

Explain what leads to the activation of the nAChR

Answer 9

Chemically gated, needs 2 ACh molecules to bind to open

Question 10

How does the nAChR lead to propagation of a signal?

Answer 10

cation channel permeable to K+ and Na+
- Na+ in → depolarisation
- chemical and electrical potentials brining it in
- K+ has chemical potential out but electrical potential in
- Net effect is Na+ in → depolarisation

Question 11

What leads to closing of the channel?

Answer 11

Prolonged exposure = desensitisation → gate closed

Question 12

What is the agonist of the nAChR?

Answer 12

nicotine (this is what it is named for)

Question 13

What are the antagonists of the nAChR?

Answer 13

• a-Tubocurarine:
  
  • from a plant, binds to nACh receptors and shuts them down → muscle paralysis
• Alpha-neurotoxins
  
  • e.g. in snake venom, affects breathing also

Question 14

Describe the 3 ways MG affects NMJ function

Answer 14

• antibodies to muscle nAChR
  
  1. attacks receptors → less receptors
  2. block receptors → less ACh binding
  3. Inflammatory response (from antibodies) → oxidative stress → damages endplate

Question 15

What are symptoms of MG, and what causes these?

Answer 15

reduced NMJ function → muscle weakness, particularly frequently used muscle
- facial muscles very frequently used, do lots of sustained contractions → MG patients have droopy eyes, less facial expression

Question 16

When could MG lead to failure of transmission?

Answer 16

sustained contractions/later impulses bc in MG, less receptors means that the normal drop in ACh may cause failure in transmission

Question 17

How is MG treated?

Answer 17

treatment = delay breakdown of ACh, block the esterase, so that ACh builds up