NMJ and muscle contraction

Question 1

What is the neuromuscular junction?

Answer 1

It is a specialised synapse between a motor neurone and a muscle fibre (effector)

Question 2

What is a synapse?

Answer 2

It is a gap or junction that allows for contact from neuron to muscle or from neuron to neuron.

Basic structure is similar throughout the system, however the arrangements can be complex. You can have 1:1 or many:1

Question 3

What are the 3 main structures in the NMJ?

Answer 3

There are 3 main structures with the NMJ:

1. Pre-synaptic nerve terminal
2. Synaptic cleft
3. post synaptic endplate region on the muscle fibre

Acetylcholine (ACh) is the neurotransmitter for voluntary striated muscle

Question 4

Describe the structures on the pre nerve and post endplate

Answer 4

• There are Ach receptors and acetylcholinesterases (in the crypts) on the post synaptic endplate.
• The motor end plate is highly folded
• There is unidirectional chemical communication between a peripheral nerve and muscle.

Question 5

What is the organisation of NMJs like?

Answer 5

There are often 2 motor units heading/ connecting with the effector. In development, motor neurones compete to be the dominant motor neurone (alpha motor neurone)

Question 6

What is the mechanism for muscle contraction through NMJ?

Answer 6

1. AP open the VGCC
2. Ca enters
3. Ca triggers exocytosis of vesicles containing Ach
4. ACh diffuse into the cleft
5. ACh binds to receptors on the post synaptic area and opens channels
6. Local currents flow from depolarised regions and adjacent region- AP is triggered and spreads along the surface of the membrane
7. ACh is broken down by acetylcholinesterase- muscle fibre response to that molecule of acetylcholine ceases.

Question 7

What’s happening at the NMJ at rest?

Answer 7

Individual vesicles release ACh at a very low rate causing miniature end-plate potentials (MEPPs)

This can be seen in the pic small potentials being created by the small volumes of ACh being released. These potentials don’t create an AP- they are graded potentials

Question 8

What are myofibres?

Answer 8

They are the final level of differentiation.

• They are covered by plasma membrane- sarcolemma
• T-tubules tunnel into the centre
• Cytoplasm called sarcoplasm- myoglobin and mitochondria present
• Network of fluid filled tubules- sarcoplasmic reticulum
• composed of myofibrils (1-2 micrometers in diameter). They extend along the entire length of myofibres- composed of two main types of protein- actin and myosin

Question 9

What are sarcomeres?

Answer 9

Each functional unit- sarcomere: composed of actin and myosin

It has dark and light bands to give a striated appearance.

Question 10

What are myofilaments?

Answer 10

Dense protein z-discs separate sarcomeres. Dark bands are A bands (thick myosin)

Light bands are I bands (thin actin)

Myosin and actin filaments overlap

Question 11

What were the observations from the sliding filament theory?

Answer 11

• During contraction, I band becomes shorter
• The A band remained the same length
• H zone narrowed or disappeared

Question 12

What is the activation and relaxation process?

Answer 12

• AP propagates along the surface membrane into the t-tubule
• DHPR- dihydropyridine receptor in t-tubule senses voltage change. Conformational change. Like to Ryr (ryanodine receptor) so Ca stored in the sarcoplasmic reticulum is released into the space around the filament
• Ca binds to troponin and tropomyosin moves to uncover the actin/myosin binding site
• A cross bridge can form
• Ca is then actively transported into the SR continuously, while APs continue (uptake rate is less than release rate)
• Ca dissociates from the troponin when free Ca declines. Tropomyosin blocks new cross bridge attachment- active force declines due to net crossbridge detachement.

Question 13

What are some disorders of NMJ?

Answer 13

They are pathological processes interfering with NMJ function causing muscle weakness:

Botulism- Botox- toxin produces an irreversible disruption in stimulation-induced acetylcholine release by the presynaptic nerve terminal. You have the will to move but does not cause muscle slide.

Myasthenia gravis (MG)- autoimmune disorder where antibodies are directed against the acetylcholine receptor. Nothing happens. In severe cases, the antibodies in the blood can be removed via plasma exchange which allows rapid improvement to occur. Or inject acetylcholinerase. Corticospinal tract, cortiobulbar tract.

Lambert-Eaton myastenic syndrome (LEMS)- autoimmune disease causd by antibodies directed against the VGCC- associated with lung cancer.