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 Neuromuscular junction?

Answer 2

A specialised Synapse that exists only between motor neurones and muscle cells.

Question 3

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

Answer 3

1. Ca concentration is much lower inside the cell than out.
2. Presynaptic terminal has an AP
3. This causes depolarisation opening the voltage gated Ca channels
4. This is sensed by synaptotagmin
5. Conformational change upon Ca binding triggers vesicle fusion with the presynaptic membrane
6. ACh is released by exocytosis.

Question 4

How is the NMJ specialised?

Answer 4

Pre synaptic - Many vesicles for large amounts of ACh release

Post Synaptic - Junctional folds increasing density of nACh receptors and there is a high density of Na channels.

Question 5

How does Ca ions induce vesicle fusion?

Answer 5

Ca ions enter into the presynaptic terminal
Synaptotagmin is the sensory for Ca ions
when Ca ions bind, there is a conformational change which triggers vesicle fusion.

Question 6

What does ACh bind to?

Answer 6

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

Question 7

What happens after ACh binds to the postsynaptic end plate?

Answer 7

• 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 8

What happens when an end plate potential is established?

Answer 8

• 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 9

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

Answer 9

because nAChR absent away from synapse

Question 10

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

Answer 10

1msec

Question 11

What is EPP generated by?

Answer 11

ligand gated channels

Question 12

Why is the threshold for AP generation easily passed?

Answer 12

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

Question 13

How does muscle contraction occur?

Answer 13

• 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 14

What happens during repolarisation?

Answer 14

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

Question 15

How do you reach a sustained contraction of a muscle?

Answer 15

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

Question 16

What is myesthenia Gravis?

Answer 16

• failure of neuromuscular junction to keep firing

- autoimmune disease of nAChR (reduced number at NMJ)

Question 17

What symptoms dies MG have?

Answer 17

muscle weakness during sustained activity

Question 18

How do you treat MG?

Answer 18

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

Question 19

What happens to ACh when its no longer required?

Answer 19

-released into the synaptic cleft and is hydrolysed by acetylcholinesterase Enzyme (AChE)