6. NMJ and muscle contraction

Question 1

Neuromuscular junction (NMJ)

Answer 1

A specialised synapse between a motor neurone and a muscle fibre

Question 2

Synapse

Answer 2

“contact or junction”
Allows for contact from neurone to muscle or from neurone to neurone.
Can be simple or complex.
Contact ratio: ranges from 1:1 for muscle to 10^3:1 in CNS

Question 3

What is the enlargement at the end of an axon pre-NMJ called?

Answer 3

Motor end plate

Question 4

What is the neurotransmitter for voluntary striated muscle?

Answer 4

Acetylcholine (ACh)

Question 5

How are motor neurones organised?

Answer 5

Into upper (in brain) and lower (in brain stem to face or spinal cord if to muscles in arms/legs)

Question 6

What innervation is received by a single muscle fibre?

Answer 6

Innervation from 1 branch of 1 motor neurone

Question 7

What may injury allow in terms of re-innervation?

Answer 7

Re-innervation of muscle that has previously been innervated by other neurones

Question 8

Describe what occurs when an AP reaches the NMJ

Answer 8

1. AP opens VGCC
2. Ca2+ enters and triggers exocytosis of vesicles
3. ACh diffuses in cleft
4. ACh binds to receptor-cation channel and opens channel
5. Local currents flow from depolarized region to adjacent region; AP triggered and spreads along surface membrane
6. ACh broken down by acetylcholine esterase (enzyme). Muscle fibre response to that molecule of ACh ceases

Question 9

Miniature end-plate potentials (MEPPs)

Answer 9

At rest, individual vesicles release ACh at a very low rate causing miniature end-plate potentials (MEPPs)
=Occasional upward deflections on graph (don’t result in muscle contraction)

Question 10

Skeletal muscle structure

Answer 10

Muscle attached to skeleton
Voluntary contraction
Made of fascicules (collection of muscle fibres surrounded by connective tissue)
Striated

Question 11

Describe the structure of myofibres

Answer 11

Covered by plasma membrane: sarcolemma
T-tubules tunnel into centre
Cytoplasm called sarcoplasm (myoglobin and mitochondria present)
Network of fluid filled tubules: sarcoplasmic reticulum
Composed of myofibrils

Question 12

Describe the structure of myofibrils

Answer 12

1-2μm in diameter
Extend along entire length of myofibres
Composed of Actin and Myosin

Question 13

What are the 2 subtypes of isotonic contraction?

Answer 13

Concentric: shortening
Eccentric: lengthening

Question 14

Describe the structure of myofilaments

Answer 14

Light and dark bands give muscle striated appearance
Do not extend along length of myofibers
Overlap and are arranged in compartments called sarcomeres (Z disc to Z disc)

Question 15

What makes up the striated appearance of myofibrils

Answer 15

Dark bands: A band, thick: myosin

Light bands: I band, thin: actin

Question 16

What observations can be made during muscle contraction?

Answer 16

I band became shorter
A-band remains same length
H-zone narrows/ disappears

Question 17

Describe the process of excitation-contraction coupling of skeletal muscle

Answer 17

An AP propagates along sarcolemma and T tubules
Reaches the Dihydropyridine receptors
Depolarisation causes a conformational change in the DHPRs
Change transmitted to Ryanodine Receptors on sarcoplasmic reticulum
RyR opens: causing Ca2+ release from intracellular stores
Ca2+ binds to Troponin and Tropomyosin moves, allowing cross bridges to attach to actin
Ca2+ actively transported into SR continuously throughout
Ca2+ dissociated from troponin when free Ca2+ declines, Tropomyosin prevents new cross bridge attachment
Active force declines due to net cross bridge detachment

Question 18

3 examples of diseases where pathological processes interfere with NMJ function

Answer 18

Botulism
Myasthenia gravis (MG)
Lambert-Eaton myastenic syndrome (LEMS)

Question 19

Botulism

Answer 19

Botulinum toxin produces an irreversible disruption in stimulation-induced ACh release by the presynaptic nerve terminal
(Stops release of ACh into synapse)
Can cause paralysis of muscles

Question 20

Myasthenia Gravis

Answer 20

An autoimmune disorder where antibodies are directed against the ACh receptor
Receptor no longer receptive to ACh, so can’t contract

Question 21

Signs and symptoms of Myasthenia Gravis

Answer 21

Personal/ family history of autoimmune diseases
Fatigable weakness
May affect ocular, bulbar, respiratory or limb muscles

Question 22

What can give Myasthenia Gravis the potential to be treated?

Answer 22

Not all receptors are blocked, so if ACh is kept in synapse longer (Not broken down by ACh esterase) muscles will respond
In severe cases the antibodies in the blood can be removed via plasma exchange which allows rapid improvement to occur.

Question 23

Lambert-Eaton myasthenic syndrome

Answer 23

An autoimmune disease caused by antibodies directed against the VGCC’s in presynaptic terminals
Ca2+ can’t enter
Associated with lung cancer

Question 24

Corticospinal track

Answer 24

Cortex + Spinal cords: signals to limbs

Question 25

Corticobulbar track

Answer 25

Cortex + Bulbar: signals to face muscles