Muscle and function

Question 1

Describe different types of muscle fibres, their means of contraction, and the trophic effects of nerves on muscles

Answer 1

Three types of skeletal muscle fibres:
- Type 1: slow twitch -> very fatigue resistant and capable of producing repeated, low-level contractions. Produces large amounts of ATP through aerobic metabolism.

• Type 2a: fast twitch oxidative -> produce fast, strong muscle contractions but prone to fatigue. Produces ATP at a fast rate via anaerobic and aerobic metabolism.
• Type 2b: Fast twitch glycolytic -> Produce short bursts of power but fatigue quickly. Produces ATP slowly via anaerobic metabolism

Question 2

Describe skeletal muscle type’s structural features

Answer 2

Cell length: 1mm - 1m
Cell diameter: 10-100 um

Long parallel cylinders, multiple peripheral nuclei, striations.

CT components: epimysium, perimysium, and endomysium

t-tubules: triad with 2 terminal cisternae, 2 per sarcomere.

No cell-cell junctions

Question 3

Describe cardiac muscle’s structural features

Answer 3

Cell length: 50-100 um
Cell diameter: 10-20 um

Short branched cylinders, single central nucleus and striations.

Only has endomysium for CT.
T-tubules is a diad with small terminal cisternae with 1 per sarcomere. Cell-cell junctions are intercalated discs

Question 4

Describe smooth muscle’s structural features

Answer 4

Cell length: 50-100 um,
cell diameter: 5-10 um

Spindle-shaped, tapering ends, single central nucleus

CT: endomysium, with sheaths

No T-tubules, but well developed sarcoplasmic reticulum.

Gap-junctions present

Question 5

Describe skeletal muscle’s functions

Answer 5

• Voluntary innervation
• SOMATIC efferent innervation
• Type 1 and 2 fibres contraction
• Regulation of contraction: Calcium causes tropomyosin movement and exposes myosin-binding sites on actin

Question 6

Describe cardiac muscle’s functions

Answer 6

• involuntary innervation
• Autonomic nervous system innervation
• Rhythmic contraction, via conductive system
• Regulation of contraction: calcium causes tropomyosin movement and exposes myosin-binding sites on actin

Question 7

Describe smooth muscle’s functions

Answer 7

• Involuntary innervation
• autonomic nervous system innervation
• Slow, partial, rhythmic and spontaneous contraction
• Regulation of contraction: by phosphorylation of myosin light chain kinase in presence of calcium - calmodulin

Question 8

Describe skeletal muscle’s growth and regeneration

Answer 8

No mitosis.
Hypertrophy is response to demand

Limited regeneration

Question 9

Describe cardiac muscle’s growth and regeneration

Answer 9

No mitosis in normal conditions.
Hypertrophies in response to demand.

No regeneration in normal conditions.

Question 10

Describe smooth muscle’s growth and regeneration

Answer 10

Mitosis is present.

Hypertrophy and hyperplasia in response to demand.

Regeneration is present.

Question 11

Describe organization of skeletal muscles (smallest to largest):

Answer 11

1. Sarcomere: actin and myosin arranged
2. Myofibril: sarcomeres lined up in a line
3. Fibre (muscle cell): bundles of myofilament in ONE muscle cell
4. Fascicles: Bundles of fibres
5. Muscle: bundles of fascicles

Question 12

Describe the different types of muscle connective tissues

Answer 12

• Epimysium -> dense irregular connective tissue sheath around entire muscle
• Perimysium -> Septa of epimysium that separates muscle into fascicles
• Endomysium -> loose connective tissue around each muscle fibre (muscle cell)

Question 13

List the components of muscle fibres

Answer 13

• Sarcoplasm -> Cytoplasm of muscle fibres
• Sarcolemma -> Plasma membrane of muscle cells
• Sarcoplasmic reticulum (sER) -> networks around myofibrils; stores contain calcium
• T-tubules -> Invaginations of sarcolemma; transmit action potential deep into muscle
• Terminal cisterna -> sER rings adjacent to T-tubules; storages of calcium inside the muscle fibre

Question 14

Describe the sarcomere (contractile unit)

Answer 14

• Thin actin filaments joined together at z-lines
• Thick myosin filaments in between actin filaments
• During contraction, myosin filaments in between actin filaments to bring z-lines closer

Question 15

Describe the motor unit

Answer 15

A single motor neuron and all the skeletal muscle fibres that are innervated by its axonal terminals.

• Action potential transfer across neuromuscular junction:
  1. Motor neuron axon terminal releases acetylcholine (ACh)
  2. ACh diffuses across synapse
  3. ACh binds with nicotinic receptors on muscle membrane
  4. Muscle membrane depolarizes

Question 16

Describe contractile proteins

Answer 16

Actinomyosin -> complex of parallel threads of actin and myosin that slide past each other during contraction

Question 17

Describe regulatory proteins:

Answer 17

• Tropomyosin -> protein that coils around actin filament and covers myosin binding sites.
• Troponin -> protein that binds tropomyosin
• When Calcium binds to troponin, the tropomyosin’s conformation changes and myosin can bind with actin

Question 18

Describe cytoskeletal proteins:

Answer 18

• Titin -> very large protein responsible for the passive elasticity of muscles; connects M-disk to Z-line and recoils muscles after stretching and prevents overstretching
• Desmin -> Protein of a specific type of intermediate filament that regulates architecture of sarcomeres

Question 19

Describe the cross-bridge cycle

Answer 19

• Cross-bridge cycle -> repeated cycle of myosin heads on thick filaments binding with thin filaments and producing force.
• Steps:
  1. calcium binds to troponin, tropomyosin changes shape, and exposes myosin binding site
  2. Myosin head binds to actin; ADP released
  3. Power stroke pulls z-line together
  4. ATP binds to myosin; myosin head releases actin
  5. ATP -> ADP causes myosin to reset conformation
  6. Go to step 2

Question 20

Describe pathology of cross-bridges

Answer 20

• Mutations in contractile proteins are often lethal or lead to muscle damage
• Hypertrophic cardiomyopathy - faulty contractile proteins in heart lead to enlargement of heart muscles to compensate

Question 21

Describe Excitation-contraction coupling

Answer 21

Excitation-contraction coupling -> link between the action potential of the sarcoplasm to the calcium release and muscle contraction by the muscle fibre.

Steps:

1. Action potential propagates along sarcoplasm and into T-tubules
2. Action potential depolarizes voltage sensory on T-tubules
3. Voltage sensors on T-tubules are coupled with adjacent calcium channels on the sarcoplasmic reticulum
4. Calcium channels release calcium into sarcoplasm

Question 22

Define ‘foot process’

Answer 22

T-tubule voltage sensor and adjacent sarcoplasmic reticulum calcium channel

Question 23

Describe myotonia

Answer 23

Myotonia: failure to relax at the end of voluntary contraction.

• Abnormal ion channels cause hyperexcitability
• Voluntary contraction leads to extended forces

Question 24

Describe myasthenia gravis

Answer 24

Autoimmune disease leading to weakening of voluntary muscle contraction

• Antibodies block nicotinic ACh receptors on muscle end plate
• Muscle depolarization due to single ACh vesicle release decrease
• AP doesn’t initiate on muscle

Question 25

Describe malignant hyperthermia

Answer 25

Release of calcium ions in all muscles cause contraction and raise in temperature.

• Mutation by sER release channel
• Triggered by anaesthesia - halothane opens sER channels

Question 26

Explain muscle fatigue

Answer 26

• Definition: reversible weakness associated with intense activity
• Muscles sore and weak but recover fully after short rest
• Fatigue due to inability of muscle to replace ATP fast enough:
  1. shortage of fuel within fibre
  2. Accumulation of metabolites (also interferes with calcium ion release)

Question 27

Explain stretch-induced muscle damage

Answer 27

• Caused by stretching active muscles (e.g. walking down hill): muscles are stretched onto descending limb of tension-length curve.
• Over stretched sarcomeres
• Loss of muscle enzymes into the blood (e.g. creatine kinase)
• Results in delayed onset muscle soreness (DOMS):
  1. next day muscles are sore and tender
  2. recovery takes days (different from fatigue)

Question 28

Outline the role of key metabolites in muscle fatigue

Answer 28

Lactic acid/H+ ions -> low pH in sarcolemma which inhibits anaerobic respiration

Magnesium/ROS -> interfere with calcium release from sER or binding to calcium ions to troponin

Question 29

Describe the cause and consequences of sarcomere stretching

Answer 29

Cause:

• Tension is applied to sarcomere while lengthening
• Muscles are maximum strength at middle length
• Sarcomeres passes into unstable descending limb of tension-length curve:
  1) If two adjacent sarcomeres are in the unstable regions: One gets longer and weaker, one gets shorter and stronger.
  2) During stretch contractions, sarcomeres can become over stretched.

Consequences:

• Sarcolemma damage
• Loss of intracellular proteins
• Inflammation (tenderness)
• Repair/replacement by satellite cells

Question 30

Describe the process of muscle regeneration

Answer 30

1. satellite cells border muscle fibres
2. satellite cells activated from muscle damage
3. satellite cells differentiate into myoblasts that dive and fuse to myotubules
4. Myotubules repair and replace damage region of muscle cell

Question 31

Outline the benefits of exercise on bone biology

Answer 31

• Exercise stimualtes bone remodelling:
  1) Bone architecture maintained to counteract stress applied
  2) New bone is laid down to maintain strength
• Lack of mechanical loading leads to bone loss
• Osteoblasts and osteocytes of mechanosensitive

Question 32

Outline the role of dystrophin in muscle cell function

Answer 32

• Cytoskeletal protein that connects contractile proteins to the cell membrane
• Reduces the membrane damage associated with over and under stretched sarcomeres
• If missing:
  1) tears in sER allows Calcium release
  2) tears in T-tubules allows leak of enzymes out of muscle fibre
  3) Satellite cells cannot keep up with required muscle repair

Question 33

Describe Duchenne muscular dystrophy:

Answer 33

• Cause: genetic disorder leading to non-functional dystrophin proteins
• X-linked genetic disorder
• 1 in 3500 males affected
• Symptoms:
  1) normal at birth but increasing muscle weakness
  2) inability to repair muscle damage
  3) Wheelchair bound at 10
  4) Death by respiratory failure at 20

Question 34

Describe the basic concepts as to how exercise can improve insulin sensitivity

Answer 34

Exercise to improve insulin sensitivity in diabetes patients:

• Rational:
  1) Reducing lipid in body reduced the inhibition of glucose uptake by fatty acids
  2) Increasing glucose metabolism in cells upregulates expression of proteins in glucose metabolism (e.g. insulin receptors and glucose transporters)

Results:

• Weight loss alone is enough to increase insulin sensitivity dramatically
• Weight loss and exercise only provides slight improvement over weight loss alone

Question 35

Explain how muscle size is increased (hypertrophy) and decreased (atrophy/cachexia)

Answer 35

No change in NUMBER of muscle fibres.

Hypertrophy:

• Muscle fibres increase in size, but not increase in number
• More sarcomeres are recruited into muscle fibre
• Cause: small number of maximal contractions

Atrophy:

• Muscle fibres become smaller and thinner with disuse
• Number of cells is constant but less sarcomeres are within each fibre
• Cause: Starvation, age, cancer, infection, lack of activity, muscular dystrophy