Neuromuscular Junction

Question 1

Where would you find a neuromuscular junction?

Answer 1

between a motor neurone and a muscle cell

Question 2

What is the role of Ca2+ in excitation-contraction coupling?

Answer 2

• Ca2+ concentration inside is much less than it is outside
• when an action potential occurs in presynaptic terminal depolarisation opens the voltage-gated Ca2+ channels
• Ca2+ enters the presynaptic terminal causing fusion of vesicles with presynaptic membrane
• acetylcholine is released

Question 3

What is the Ca2+ receptor?

Answer 3

synaptotagmin

Question 4

What does ACh bind to?

Answer 4

nicotinic ACh receptors on post-syanptic end plate (ligand gated ion channel)

Question 5

What happens after ACh binds to the postsynaptic end plate?

Answer 5

• channel opens which is permeable to Na+ and K+
• Em of muscle cell = -90mV (normally)
• Na+ influx is greater than K+ efflux so Em becomes more positive
• End-plate potential reaches (-20mV) (postsynaptic potential)

Question 6

What happens when an end plate potential is established?

Answer 6

• EPP initiates an action potential in muscle (which is greater than threshold)
• AP travels through muscle cell
• EPP decays as it does away from the end plate
• EPP causes the opening of voltage gated channels

Question 7

Why does the EPP decay as it moves away from the end plate?

Answer 7

because nAChR absent away from synapse

Question 8

How long does it take for a presynaptic AP to cause a EPP?

Answer 8

1msec

Question 9

What is EPP generated by?

Answer 9

ligand gated channels

Question 10

Why is the threshold for AP generation easily passed?

Answer 10

high density of voltage-gated Na+ channels at the end plate

Question 11

How does muscle contraction occur?

Answer 11

• action potential moves through T-tubule system
• allows transmission of AP deep into the muscle fibre to separate myofibrils
• DHP receptor (calcium voltage-gated channel) has a structural change due to AP this causes the calcium release channel to move-opening to Ca2+ channel which triggers muscle contraction

Question 12

What happens during repolarisation?

Answer 12

• DHP receptor no longer activated so calcium release channel moves back in place
• calcium ions bind to calsequestrin

Question 13

How do you reach a sustained contraction of a muscle?

Answer 13

reach around 40Hz by having a high rate of firing (summation of muscle contractions)

Question 14

What happens to ACh when its no longer required?

Answer 14

-released into the synaptic cleft and is hydrolysed by acetylcholinesterase

Question 15

What is myesthenia Gravis?

Answer 15

• failure of neuromuscular junction to keep firing

- autoimmune disease of nAChR (reduced number at NMJ)

Question 16

What symptoms dies MG have?

Answer 16

muscle weakness during sustained activity

Question 17

How do you treat MG?

Answer 17

using ACHE inhibitors, slows down the breakdown of ACh prolonging the single