NMJ

Question 1

What is meant by the NMJ

Answer 1

A specialised synapse between a motor neuron and a muscle fibre.

Question 2

How does the neuron innervate the muscle fibre

Answer 2

Lots of branches of the motor neuron on the muscle fibre.

Question 3

When are neuromuscular diseases particularly dangerous

Answer 3

When they affect muscles that keep you alive, for example your diaphragm.

Question 4

What are motor neurons divided into

Answer 4

Upper and lower, depending on where they go from the brain to the brainstem or the brain to the spinal cord.

Question 5

How can we take advantage of action potentials clinically

Answer 5

We can take advantage of the flow of charge to record action potentials, when monitoring the activity of muscle fibres at rest and during contraction. This allows us to diagnose disease, differentiate between causes and monitor the progression of the disease.

Question 6

Describe, basically, synapses

Answer 6

Allows for contact from neuron to muscle or from neuron to neuron.

Basic structure is similar throughout the nervous system.

Arrangements can be simple or complex.

Contact ratio – ranges from 1:1 for muscle to 103:1 in the CNS

Question 7

In the NMJ what is the synaptic cleft the space between

Answer 7

The motor neuron and the muscle fibres

Question 8

What is the end of the axon called

Answer 8

The motor end plate, which is relatively large.

Thin axon which enlarges near the muscle fibre.

Question 9

Where do many neuromuscular problems occur

Answer 9

In the calcium ion channels on the pre-synaptic terminal

Question 10

What is the key feature of neuromuscular disease

Answer 10

Muscle contraction cannot take place
However, there are many things that can go wrong which all lead to this. Therefore, it is important to determine the cause, to ensure that the appropriate treatment is given.

Question 11

What are the main structures constituting the NMJ

Answer 11

presynaptic nerve terminal
synaptic cleft
postsynaptic endplate region on the muscle fibre

Question 12

Describe the structure of the NMJ

Answer 12

A specialized structure incorporating the distal axon terminal and the muscle membrane that allows for the unidirectional chemical communication between peripheral nerve and muscle

Question 13

What is the neurotransmitter for voluntary striated muscle

Answer 13

Acetylcholine serves as the neurotransmitter for voluntary striated muscle

Question 14

Where are the cell bodies for motor neurons found in the spinal cord

Answer 14

In the anterior horn of the grey mater,

Question 15

What does a single muscle fibre receive innervation from

Answer 15

One branch of a single motor neurone.

Initially, during development, received more, but selectively inhibited some to leave one.

Question 16

Describe the difference between upper and lower motor neurons

Answer 16

Upper- brain stem and brain- where signals for voluntary movement originate
Lower- brainstem- face spinal cord- limbs and trunk

Question 17

Why is it important clinically that each muscle fibre only receives innervation from one branch

Answer 17

When the nerves are cut, due to trauma, the regrowth of nerves permits the innervation of more than one muscle fibre, different action potentials recorded for injured and uninjured nerve
Nerves sprout and innervate muscle fibres that were previously innervated by other muscle fibres.

Question 18

Describe how muscle contraction is initiated

Answer 18

The NMJ is responsible for initiating muscle contraction.
Action potential open V-gated Ca2+ channels
Ca2+ enters
Ca2+ triggers exocytosis of vesicles
Acetylcholine diffuses in cleft
Acetylcholine binds to receptor-cation channel & opens channel
Local currents flow from depolarized region and adjacent region; action potential triggered and spreads along surface membrane
Acetylcholine broken down by acetylcholine esterase (enzyme). Muscle fibre response to that molecule of Acetylcholine ceases

Question 19

Describe the roles of SNAREs in vesicle docking

Answer 19

SNAREs on the vesicle (v-SNAREs) interact with complementary SNAREs on the target membrane (t-SNAREs), firmly docking the vesicle in place

Question 20

Describe the release of Ach from the NMJ

Answer 20

Released periodically at rest, in discrete amounts (which shows that it is packaged in vesicles), causing upward deflections on the EMG, but the depolarisation is not enough to generate an action potential.
At rest, individual vesicles release ACh at a very low rate causing miniature end-plate potentials (MEPPs)
Set number of molecules in each vesicle (amplitudes are similar)

Question 21

Describe smooth muscle

Answer 21

Surrounds circular and hollow organs, under involuntary control

Question 22

What is the muscle made up of

Answer 22

Fascicles which are collections of muscle fibres surrounded by connective tissue, myofibrils within muscle fibres- gives muscle its striated appearance

Question 23

Describe the myofibres

Answer 23

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

Question 24

What gives skeletal muscle its striated appearance

Answer 24

The discrete arrangement of proteins within the striated muscle.

Question 25

Describe the myofibrils

Answer 25

1-2μm in diameter
Extend along entire length of myofibres
Composed of two main types of protein – actin and myosin

Question 26

When is more force generated

Answer 26

As muscles get longer. Eccentric contractions- where most damage occurs.

Question 27

Describe myofilaments

Answer 27

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

Question 28

What are A and I bands named after

Answer 28

Their effects on polarised light
Dark bands – A band (thick - myosin)
Light bands – I band (thin - actin

Question 29

What are Z lines, M lines and H bands named after

Answer 29

Location
Dense protein Z-discs separate sarcomeres
Myosin and actin filaments overlap- H zone

Question 30

Describe the observations of the sliding filament model

Answer 30

During contraction I band became shorter
A-band remained same length- they are pulling the actin over it
H-zone narrowed or disappeared

Question 31

Describe the activation and relaxation process

Answer 31

Action potential propagates along surface membrane and into T-tubules
DHP (dihydropyridine) receptor in T-tubule membrane: senses V & changes shape of the protein link to Ryanodine receptor, opens the Ryanodine receptor Ca2+ channel in the SR membrane; Ca2+ released from SR into space around the filaments
Ca2+ binds to Troponin & Tropomyosin moves allowing
Crossbridges to attach to actin
Ca2+ is actively transported into the SR continuously while action potentials continue. ATP- driven pump (uptake rate < or = release rate).
Ca2+ dissociates from TN when free Ca2+ declines; TM block prevents new crossbridge attachment; Active force declines due to net crossbridge detachment

Question 32

What happens in rigor mortis

Answer 32

No energy from ATP to detach myosin from actin

But eventually gets broken down- the muscles become flaccid again.

Question 33

What happens once the action potential stops

Answer 33

No release of calcium

SR constantly transporting calcium, all gets taken up now

Question 34

Describe disorders of the NMJ

Answer 34

Pathological processes interfering with NMJ function can cause muscle weakness
Examples:
Botulism
Myasthenia gravis (MG)
Lambert-Eaton myastenic syndrome (LEMS)

Question 35

Describe botulism

Answer 35

Botulinum toxin produces an irreversible disruption in stimulation-induced acetylcholine release by the presynaptic nerve terminal
Paralyses the muscles.
Potentially fatal- especially if diaphragm is paralysed

Question 36

Describe Myasthenia Gravis

Answer 36

An autoimmune disorder where antibodies are directed against the acetylcholine receptor.
There may be a personal or family history of other autoimmune diseases. It cause fatigable weakness (i.e. becomes more pronounced with repetitive use) and may affect the ocular, bulbar, respiratory or limb muscles.
Antibodies are detected in nearly 90% of cases and EMG examination will confirm the diagnosis.
In severe cases the antibodies in the blood can be removed via plasma exchange which allows rapid improvement to occur.

Question 37

Why can muscles not contract in myasthenia gravis

Answer 37

No acetylcholine binding to receptors on the postsynaptic terminal. Hence no calcium influx into the muscle- no contraction

Question 38

What does bulbar relate to

Answer 38

The brainstem

Question 39

Describe corticospinal and corticobulbar tracts

Answer 39

Corticospinal- cortex to spinal cord- limbs

Corticobulbar- cortex to brainstem- face (eyes, talking, forming expressions)

Question 40

How can we treat myasthenia gravis

Answer 40

Not all receptors blocked
Inhibit acetylcholinesterase
Keep more Ach in synaptic cleft
More likely to bind to available receptors
Test for this disease, inject this drug, symptoms disappear almost immediately.

Question 41

What is Myasthenia gravis associated with

Answer 41

Lymphoid hyperplasia and tumours of the thymus. Weakness may respond to surgical thymic removal, especially in young patients with short history. Otherwise treatment is with immunosuppression and anti-cholinesterases (pyridostigmine, neostigmine).

Question 42

Describe Lambert-Eaton myasthenic syndrome

Answer 42

an autoimmune disease caused by antibodies directed against the voltage-gated calcium channel (VGCC) - associated with lung cancer.
No acetylcholine release, no contraction

Question 43

How could we treat Lambert-Eaton myasthenic syndrome

Answer 43

Release a compound that mimics acetylcholine

Initially lessened with exercise.