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BIOM30002 > lecture 31 > Flashcards

lecture 31 Flashcards

1
Q

Learning objectives?

A
  • structure and function of skeletal muscle
  • pathologic processes affecting human skeletal muscle
    → model: the human muscular dystrophies
  • clinical presentation of the muscular dystrophies
    → model: duchenne muscular dystrophy, most common MD, affecting 1/3500 boys
  • treatment of the muscular dystrophies
  • advances in therapeutics of the muscular dystrophies
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2
Q

objectives for this lecture?

A
  • the structure of human skeletal muscle
    • myofibrils
    • sarcomeres
  • the contractile function of human muscle
    • the ‘sliding filament’ theory
  • different fibre types in human skeletal muscle
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3
Q

What are muscle diseases?

A
  • muscle tissue consists of highly specialised cells/fibres which contract to actively generate force
  • shortening of muscles moves joints, resulting in motion
  • because of this characteristic, muscle tissue enables motion and maintenance of posture
  • muscle tissue also engenders heat production
  • based on structural and function characteristics, muscle tissue is classified into three types: cardiac, smooth, and skeletal
  • muscle disorders affect one or more of these tissue types
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4
Q

What are myopathies?

A
  • genetic and acquired disorders of the muscle contractile apparatus
  • myopathies are disorders of the muscle contractile apparatus, with characteristic pathologic changes which do not generally change greatly over time i.e. are usually static
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5
Q

What are muscular dystrophies?

A
  • genetic disorders of the supporting structures e.g. sarcolemmal proteins and protiens which anchor the contractile apparatus in place cause muscular dystrophies
  • dystrophies are progressive disorders in which muscle pathology is characterised by degeneration and regeneration of muscle fibres
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6
Q

What is skeletal muscle?

A
  • by definition, is attached to bone
  • can be made to contract or relax by conscious control (voluntary)
    – extra-ocular (muscles around eyes super specialised), limbs, truncal (vary in structure according to function)
  • it is striated: fibres (cells) contain alternating light and dark bands (striations) perpendicular to their long axes
  • skeletal muscle fibres vary in structure and function
    – variable colour depending on myoglobin content
    → myoglobin: a protein, stores oxygen for mitochondria
    – fibres contract with different velocities, depending on their ability to split ATP
    – variable metabolic processes used to generate energy
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7
Q

How are smooth and skeletal muscle similar? different?

A
  • both are multinucleated and contractile

smooth muscle: dense bodies, intercalated
skeletal muscle: parallel fibres, separate from each

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8
Q

What is the structure of skeletal muscle?

A
  • each muscle belly is made up of muscle cells, or fibres
  • each individual fibre consists of a membrane (sarcolemma) containing muscle tissue (myofibrils) and sarcoplasm
  • myofibrils are surrounded by sarcoplasm and together make up the contractile components of muscle
  • muscle fibres are striated and multinuclear, and grouped into bundles (called fasciculi) of myofibrils
  • fibres within each bundle are surrounded by connective tissue called endomysium
  • each fasciculus (bundle) is surrounded by connective tissue (perimysium)
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9
Q

What is the substructure of skeletal muscle?

A
  • each myofibril is organised into sections along its length
  • each section is called a sarcomere
  • sarcomeres are repeated along the length of muscle fibres
  • the sarcomere is the smallest contractile portion of a muscle fibre
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10
Q

What is the sarcomere?

A
  • the basic unit of skeletal muscle
  • Z disc to Z disc
  • dark and light represents areas of overlapping actin and myosin filaments
  • during contraction this bands move relative to each other and work to short the distance between z discs thus shortening the muscle overall
  • 80 or 100 proteins in each sarcomere and mutations in any one can lead to myopathies
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11
Q

What is the I band?

A
  • region of the sarcomere that contains only actin filaments
  • isotropic
  • aligned actin filaments
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12
Q

What is the A band?

A
  • overlapping/aligned actin and myosin filaments

- anisotropic

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13
Q

What is the H zone?

A
  • myosin only

- centre of sarcomere

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14
Q

What is the sarcoplasm?

A
  • the sarcoplasm contains glycogen, fat particles, enzymes and mitochondria which support muscle contraction
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15
Q

What is the Z disc?

A
  • limit of sarcomere, sited within I band
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16
Q

What is the M line?

A
  • central anchor of sarcomere
17
Q

What are the two main types of protein filament in the sarcomere?

A
  • the myofibrils encased by sarcoplasm include two main types of protein filament (myofilament): actin and myosin
  • myosin (thick filaments) and actin (thin filaments) run in parallel to each other along the length of muscle fibres
  • myosin has tiny globular heads protruding from it at regular intervals - these are called cross-bridges and play a pivotal role in muscle action
  • sarcomeric contraction is via sliding filaments
18
Q

What multiple protein components are involved in muscle contraction?

A
  • actin
  • tropomyosin
  • troponin
  • all interact with myosin
  • during muscle contraction, actin filaments slide against myosin filaments
19
Q

How does muscle contraction occur?

A
  • by sliding filaments
  • at rest, tropomyosin covers myosin binding sites of actin molecules
  • tropomyosin must be moved to uncover the binding sites on actin
  • calcium ions released by muscle action potential bind with troponin molecules and alter the structure of tropomyosin, forcing it to reveal cross-bridge binding sites on actin
  • myosin heads bind to actin, forming cross-bridges
  • formation of cross bridges between myosin and actin causes release of ADP and Pi
  • this changes the shape of the myosin head and generates a sliding movement of actin toward the centre of the sarcomere
  • this pulls the two Z discs together i.e. contracts the muscle fibre to produce a power stroke
  • when a new ATP molecule attaches to the myosin head, the cross-bridge between the actin and tmyosin breaks, returning the myosin head to its unattached position
20
Q

What causes muscle contraction?

A
  • activation of muscle cells follows release by motor neurons of the neurotransmitter acetylcholine (ACh)
  • ACh crosses the neuromuscular junction (the synapse between the terminal bouton of the neuron and the muscle cell)
  • acetylcholine binds to post-synaptic nicotinic ACh receptors
    → causes a change in receptor conformation
    → causes an influx of sodium uons and initiation of post-synaptic action potential in muscle
  • muscle action potential travels along T (transverse) tubules until it reaches the sarcoplasmic reticulum
  • the action potential changes the permeability of the sarcoplasmic reticulum, allowing the flow of calcium ions into the sarcomere
  • the outflow of calcium allows the myosin heads access to the actin cross-bridge binding sites, permitting muscle contraction
21
Q

What are the supporting proteins?

A
  • the dystrophin-associated gylcoprotein complex: alpha-dystroglycan etc
  • the sarcoglycans
  • dystrophin
  • proteins of the nuclear envelope: emerin and lamin A
  • it is loss of these structures that tends to be associated with muscular dystrophies
22
Q

What is muscle metabolism?

A
  • muscle contraction requires ATP as an energy source
  • ATP can be obtained from several sources:
    – within the fibre: ATP available in fibres can maintain muscle contraction for several seconds (explosive movement)
    – creatine phosphate: a high energy molecule stored in muscle cells, transfers its high-energy phosphate group to ADP to form ATP
    → CrPo4 in muscle cells generates enough ATP to maintain contraction for about 15 seconds
    – glucose stored within the cell as glycogen
    → in glycogenolysis, glycogen is broken down to release glucose
    → ATP is then generated from glucose by cellular respiration
    – glucose and fatty acids obtained from the blood stream: when energy requirements are high, glucose from liver glycogen and fatty acids from adipose cells and the liver are released into the bloodstream. ATP is generated from these energy rich molecules by cellular respiration
23
Q

What is cellular respiration?

A
  • the process by which ATP is obtained from energy-rich molecules

anaerobic respiration or aerobic respiration

24
Q

What are advantages and disadvantages of anaerobic respiration?

A

++
anaerobic respiration is rapid and it does not require oxygen

––
generates only two ATPs and produces lactic acid

25
Q

What is anaerobic respiration?

A

(glycolysis)
- no oxygen is present
- glycose is broken down to pyruvic acid, and two ATP molecules are generated
- pyruvic acid is converted to lactic acid
- lactic acid diffuses from muscle into the bloodstream and then into the liver
- liver enzymes then convert lactic acid back to pyruvic acid and, in the presence of oxygen, pyruvic acid can enter the mitochondria

26
Q

What is aerobic/oxidative respiration?

A
  • in aerobic respiration, pyruvate (from glycolysis) and fatty acids (from the bloodstream) are broken down, producing H2O and CO2 (carbon dioxide) and regenerating the coenzymes for glycolysis
  • requires oxygen
  • produces 36 ATP molecules (including the two from glycolysis)
  • aerobic respiration has advantages and disadvantages:
    → advantages: aerobic respiration generates a large amount of ATP
    → dis: aerobic respiration is relatively slow and requires oxygen
27
Q

What is the timeline of cellular respiration in muscle?

A
  • when the ATP generated from creatine phosphate is depleted, the immediate requirements of contracting muscle fibres force anaerobic respiration to begin
  • anaerobic respiration can supply ATP for about 30 seconds
  • if muscle contraction continues, aerobic respiration, the slower ATP-producing pathway, begins and produces large amounts of ATP as long as oxygen is available
  • eventually oxygen is depleted and aerobic respiration stops
  • ATP production by anaerobic respiration may still support some furhter msucle contraciton
  • ultimately accumulation of lactic acid from anaerobic respiration and depletion of resources (ATP, oxygen, and glycogen) lead to muscle fatigue, and muscle contraction stops
28
Q

What are fibre types in skeletal muscle?

A

Type I: red fibres
- slow oxidative, slow twitch, fatigue resistant
contain
- large amounts of myoglobin, many mitochondria
- many blood capillaries
- generate ATP aerobically (oxidative)
- split ATP at a slow rate
- slow contraction velocity, resistant to fatigue
- found in large numbers in postural muscles
- needed for aerobic activities like long distance running

TypeIIA ‘red’ fibres
- fast oxidative (fast twitch A, fatigue-resistant)
contain:
- large amounts of myoglobin, many mitochondria, many capillaries
- high cpacity for generating ATP by oxidation
- split ATP at a very rapid rate, hence high contraction velocity
- resistant to fatigue but not as much as slow oxidative fibres
- needed for middle distance running and swimming

TypeIIB (also known as IIX) ‘white’

  • fast glycolytic (also called fast twitch B or fatigable fibres)
    contain:
  • low myoglobin content, few mitochondria, few capillaries
  • large amount of glycogen, split ATP very quickly, anaerobic glycolysis
  • fatigue easily
  • needed for sports like sprinting
29
Q

What is the fibre content of muscles?

A
  • individual muscles are a mixture of all three types of muscle fibres
    → proportions vary depending on the action of that muscle
  • there are no sex or age differences in fibre distribution
  • the total number of muscle fibres is constant throughout life
  • excerise can induce changes in the fibres of skeletal muscle
    → endurance athletes have more type I fibres
    → sprinters have more type IIB fibres
  • if a weak contraction is needed only type I motor units activate
  • if a stronger contraction is required, type II A fibres also activated
  • maximal contractions use type IIB/X fibres - always activated last

BIOM30002 (36 decks)

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