Muscle

Question 1

Classify three types of muscle

Answer 1

1. Skeletal Muscle (striated)
2. Cardiac Muscle (striated)
3. Smooth Muscle (non-striated)

Question 2

Describe the Ultrastructure appearance of skeletal muscle and state which bands contain actin, myosin or both

Answer 2

MHAZI - The M line is in the H band, which is in the A band. The Z line is in the I band.
The Thin Filament is Actin.
The Thick filament is Myosin.

Question 3

What is the structure of actin?

Answer 3

Actin, tropomyosin and troponin molecules form the thin (actin) filaments of skeletal and cardiac muscle.
A troponin complex is attached to each tropomyosin molecule, covering the binding sites for the myosin filament.

Question 4

What is the structure of myosin?

Answer 4

Each thick (myosin) filament consists of many myosin molecules, whose heads protrude at opposite ends.

Question 5

How does binding of myosin head to actin binding sites occur?

Answer 5

When increased amounts of ionic calcium bind to TnC of troponin, a conformational change moves tropomyosin away from actin’s binding sites. This displacement allows myosin heads to bind actin, and contraction begins.

Question 6

Give process of muscle contraction

Answer 6

Stage 1 of contraction – Attachment
Rigor configuration: myosin head is tightly bound to actin molecule. In death, lack of ATP perpetuates this binding (rigor mortis).
Stage 2 of contraction – Release
ATP binds the myosin head causing it to uncouple from the actin filament.
Stage 3 of contraction – Bending
Hydrolysis of ATP causes the uncoupled myosin head to bend & advance a short distance (5nm)
Stage 4 of contraction – Force Generation
The myosin head binds weakly to the actin filament causing release of inorganic phosphate, which strengthens binding, and causes the ‘power stroke’ in which the myosin head returns to its former position.
Stage 5 of contraction – Reattachment
The myosin head binds tightly again and the cycle can repeat. Individual myosin heads attach and flex at different times causing movement.

Question 7

Describe the mechanism of innervation of muscle and excitation contraction coupling

Answer 7

1. Upon the arrival of an action potential at the presynaptic neuron terminal, voltage-dependent calcium channels open and Ca2+ ions flow from the extracellular fluid into the presynaptic neuron’s intracellular fluid.
2. This influx of Ca2+ causes neurotransmitter-containing vesicles to dock and fuse to the presynaptic neuron’s cell membrane. Fusion of the vesicular membrane with the presynaptic cell membrane results in the release of Ach into the synaptic cleft.
3. Acetylcholine diffuses across the synaptic cleft and binds to the nicotinic acetylcholine receptors bound to the motor end plate.
4. These postsynaptic receptors are ligand-gated ion channels, and when they bind acetylcholine, they open, allowing sodium ions to flow in and potassium ions to flow out of the muscle’s cytosol – depolarization of the sarcolemma. This depolarization spreads into the T tubules.
5. Voltage sensor proteins of the T tubule membrane change their conformation
6. Gated Ca2+-release channels of adjacent terminal cisternae are activated by the proteins change in conformation
7. Ca2+ is rapidly released from the terminal cisternae into the sarcoplasm
8. Ca2+ binds to the TnC subunit of troponin
9. The contraction cycle is initiated and Ca2+ is returned to the terminal cisternae of the sarcoplasmic reticulum.

Question 8

Explain the macrostructure of muscle

Answer 8

Epimysium covers muscle
Many fascicles made up of muscle fibres (cells) within
Perimysium surrounds fascicles
Endomysium surrounds muscle fibres within fascicle

Question 9

What lies between muscle fibres and collagen bundles in tendons?

Answer 9

Sarcolemma

Question 10

Explain the hierarchical composition of a typical skeletal muscle outlining the principal components at molecular, organellar, cellular, histological and regional anatomical levels

Answer 10

Typical skeletal muscles are composed of…
Fascicles, which are composed of…
Muscle fibres (cells), which are composed of…
Myofibrils, which are composed of…
Myofilaments – actin and myosin.

Question 11

Give 6 features of fast twitch muscle fibres

Answer 11

White in colour
Contract very quickly and powerfully (sprinting, eyemovement)
Energy released through anaerobic respiration
Lots of neuromuscular junctions
Few mitochondria
Few myoglobin

Question 12

Give 6 features of slow twitch muscle fibres

Answer 12

Red in colour
Contract slowly for a long period of time (running, postural muscles)
Energy released through oxidative phosphorylation
Fewer neuromucular junctions
Lots of mitochondria
Lots of myoglobin

Question 13

Give five features of skeletal muscle

Answer 13

Striated T tubles in line with A-I band junction
Multinucleated at periphery of cells
Voluntary control
Rapid, forceful

Question 14

Give five features of cardiac muscle

Answer 14

Striations
Branching of muscle fibres
Centrally positioned nuclei (1 or 2 per cell)
Intercalated discs between muscle fibres for electrical and mechanical coupling
Gap junctions (for electrical coupling)
T tubules inline with Z line

Question 15

Give five features of smooth muscle

Answer 15

Not striated, no sarcomeres, no t tubules
Cells are spindle shaped
Contraction is slower and more sustained
Responds to stimuli in form of never signals, hormones, drugs and blood gasses
Thick and thin filaments arranged diagonally in cell
Capable of being stretched

Question 16

How can skeletal muscles repair themselves?

Answer 16

• Cells cannot divide
• Hyperplasia following mitotic activity of satellite cells
• Hypertrophy following fusion of satellite cells with existing muscle
• Gross damage repaired by connective tissue
• If nerve or blood supply interrupted, muscle fibres replaced by fibrous tissue

Question 17

Can cardiac muscle repair themselves? What occurs after damage?

Answer 17

Incapable of regeneration

Following damage, fibroblasts invade, divide and lay down scar tissue.

Question 18

Can smooth muscles repair itself? Where is this particularly evident?

Answer 18

Cells retain their mitotic activity and can form new smooth muscle cells
This ability is particularly evident in the pregnant uterus where the muscle wall becomes thicker by hypertrophy (swelling) and by hyperplasia (mitosis) of individual cells

Question 19

What do purkinje fibres do?

Answer 19

transmit action potentials to the ventricles from the atrioventricular node

Question 20

Describe structure of purkinje fibres

Answer 20

large cells with:
Abundant glycogen
Sparse myofilaments
Extensive gap junction sites

Question 21

Why are purkinje fibres important?

Answer 21

They conduct action potentials rapidly compared to regular cardiac muscle. This rapid conduction enables the ventricles to contract in a synchronous manner.

Question 22

How does skeletal muscle remodelling take place?

Answer 22

continual process. The replacement of contractile proteins happens in ~2 weeks…Destruction > Replacement = Atrophy Replacement > Destruction = Hypertrophy

Question 23

Give three ways in which atrophy can occur

Answer 23

Disuse atrophymuscle fibres don’t die but shrink and weaken
Agepast the age of 30 muscle mass decreases
Denervationatrophy; muscle no longer receives contractile signals that are required to maintain normal size

Question 24

What is hypertrophy?

Answer 24

An increase of muscle mass from work performed against load leads to:
More contractile proteins, increase in fibre diameter.

Question 25

Give three metabolic changes as a result of hypertrophy

Answer 25

Increased enzyme activity for glycolysis, increased mitochondria, increased stored glycogen

Question 26

Outline what occurs to ACh at neuromuscular junction

Answer 26

ACh is terminated by acetylcholinesterase.
At high motor neuron firing rates, ACh release decreases(Only 25% of ACh receptors need to be occupied to open the sodium channels on the motor end plate)

Question 27

What happens in myasthenia gravis?

Answer 27

An autoimmune destruction of the end-plate ACh receptors

Loss of junctional folds at the end-plateA widening of the synaptic cleft

Question 28

What is the crisis point of myasthenia gravis?

Answer 28

when it affects respiratory muscles

Question 29

Give four symptoms of Myasthenia Gravis

Answer 29

Fatigability and sudden falling due to reduced ACh release
Drooping eyelids (placing ice on the eyelids decreases acetylcholinesterase activity, therefore treats)
Double vision
Effected by general state of health and emotion

Question 30

What is a treatment for Myasthenia Gravis/

Answer 30

Acetylcholinesterase inhibitors

Question 31

How does botulism work?

Answer 31

Toxins block ACh release

Question 32

What occurs in organophosphate poisoning?

Answer 32

Irreversibly inhibits acetylcholinesterase, therefore ACh remains in the receptors and muscle stays contracted.

Question 33

What is Duchenne’s muscular dystrophy?

Answer 33

Recessive x-linked condition
Complete absence of dystrophin causing:
- Muscle fibres to tear themselves apart on contraction
- Enzyme creatine (phospho)kinase liberated into serum
- Calcium enters cell causing cell death (necrosis)
- Pseudohypertrophy (swelling) before fat and connective tissue replace muscle fibres

Question 34

Give two symptoms of duchenne’s

Answer 34

Early onset, Gower’s sign (use of hands on knees to generate strength)
Contractures (imbalance between agonist and antagonist muscle)

Question 35

Give a treatment for duchenne’s

Answer 35

Steroid therapy (prednisolone)

Question 36

What is malignant hyperthermia?

Answer 36

autosomal dominant disorder that causes a life threatening reaction to certain drugs used for general anaesthesia.

Question 37

What does Succinylcholine do in someone with malignant hyperthermia?

Answer 37

Causes uncontrolled increase in skeletal muscle oxidative metabolism, quickly overwhelming the body’s capacity to supply O2, remove CO2 and regulate body metabolism.Circulatory collapse and death.

Question 38

How is malignant hperthermia treated?

Answer 38

by the correction of hyperthermia, acidosis and organ dysfunction, discontinuation of triggering agents and the administration of dantrolene.

Question 39

What does Dantrolene do?

Answer 39

Dantrolene is a muscle relaxant, which works by preventing the release of calcium.