Sarcomere Structure Flashcards

1
Q

What is the structure of striated muscle?

A

• Whole muscle is made up of bundles of fascicles
• Each fascicle is made up of a series of fibres
• Each fibre made up of elements called
myofibrils
• Each myofibril made up of repeating units (sarcomeres) consisting of interdigitating filaments (myofilaments)

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2
Q

Discuss muscle development

A
  • Myosatellite cells (mesenchymal cells) in each myotome give rise to myoblasts (mononuclear skeletal muscle precursors) , which mature into myocytes (multinucleated cells)
  • Myotubes synthesise contractile proteins to form myofilaments
  • Myostatin inhibits this process of differentiation
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3
Q

Discuss the structure of sarcomere

A
  • Sarcomeres are highly organised within skeletal & cardiac muscle and give a striped appearance – striated muscle
  • A sarcomere is the portion of a myofibril that lies between two successive Z disks
  • Contractile proteins
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4
Q

What contractile proteins are present in sarcomeres?

A

• Thin filaments (actin protein - 5-8nm dia; 1
μm length)
• Thick filaments (myosin protein - 10nm dia, 1.6 μm length)
• I band (isotropic) represents actin filaments
• A band (anisotropic) represents myosin filaments

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5
Q

What are the structural proteins of sarcomere?

A
  • α-actinin
  • Titin
  • Nebulin
  • Dystrophin
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6
Q

What role does α-actinin play in sarcomere?

A

– Part of spectrin family of actin-binding proteins

– Binds end of thin filaments to Z discs

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7
Q

What role does titin play in sarcomere?

A

– largest known protein (approx. 25,000 aa)
– Binds end of thick filaments (M line) to Z discs
– different titin isoforms
- leads to different elasticity of different muscle types

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8
Q

What role does nebulin play in sarcomere?

A

– actin-binding protein which is localized to the I-
band
– large protein (600-900 kDa) and binds as many as 200 actin monomers
– thin filament “ruler” and regulates thin filament length during sarcomere assembly

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9
Q

What role does dystrophin play in sarcomere?

A

– Large protein associated with Z disks

– Helps align Z disks with disks in adjacent myofibrils

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10
Q

What is present in the I band of a sarcomere?

A

thin filaments only

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11
Q

What is present in the H zone of a sarcomere?

A

thick filaments only

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12
Q

What is present in the M line of a sarcomere?

A

thick filaments linked with accessory proteins

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13
Q

What is present in the outer edge of the A band of a sarcomere?

A

thick and thin filaments overlap

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14
Q

What are thin filaments in sarcomere made of?

A

• Thin filaments consist of 3 proteins
– Actin
– Tropomyosin
– Troponin

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15
Q

What is the structure of thin filaments in sarcomere?

A
  • Backbone is double-stranded α-helical polymer of actin molecules (F-actin)
  • Tropomyosin molecules consist of 2 identical α-helices, coil around groove formed by actin
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16
Q

What is tropomyosin?

A

– Regulatory protein

– Overlaps binding sites on actin for myosin and inhibits interaction when in the relaxed state

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17
Q

What is troponin?

A

a heterotrimer
– Troponin T (binds to tropomyosin)
– Troponin I (binds to actin and inhibits contraction
– Troponin C (binds Ca2+)

– Ca2+ binding to troponin regulates skeletal muscle contraction because it moves the tropomyosin away and allows myosin to interact with the actin

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18
Q

What does Ca2+ binding to troponin do?

A

regulates skeletal muscle contraction because it moves the tropomyosin away and allows myosin to interact with the actin

19
Q

What are thick filaments in sarcomere?

A

• Thick filaments are bipolar assemblies of multiple myosin-II molecules

20
Q

What is myosin-II made of?

A

• Each myosin-II molecule consists of
– 2 intertwined heavy chains
– 2 regulatory light chains (MLC-2) (regulates ATPase activity of myosin)
– 2 essential light chains (MLC-1) (stabilizes myosin head)
– Structural related to calmodulin siperfamily

21
Q

How does Ca2+ modulate contraction?

A

through regulatory proteins rather than direct interaction with contractile proteins

22
Q

What occurs to regulatory proteins in cross bridge cycling without Ca2+?

A

regulatory proteins act to inhibit actin-myosin interactions

23
Q

What role does troponin C play in the initiation of cross bridge cycling?

A

• Troponin C is key Ca2+ sensitive regulator
– 2 high affinity binding sites (help in binding troponin C to thin filament)
– 2 low affinity binding sites (binding of Ca2+ to these sites brings about conformational change in troponin complex)

24
Q

Describe the initiation of cross bridge cycling

A
  • When [Ca2+]i rises and Ca2+ binds to TnC a conformational change of proteins occurs
  • Troponin I moves away from actin filament
  • Troponin T pushes tropomyosin away from actin binding site
  • As long as Ca2+ is present, multiple cross-bridges cycles can occur and muscle shortens
  • When [Ca2+]i falls, Ca2+ dissociates from TnC leading to a reversal of the conformational change
25
Q

What areas of the sarcomere move during contraction?

A

Both the H zone and I band shorten

26
Q

What first initiates contraction of muscle?

A

cerebral cortex which acts via α-motor neurons

27
Q

What occurs to motor neurons in the neuromuscular junction?

A

Motor neurons flattened to form motor endplate

28
Q

What neurotransmitters are used at the motor endplate in contraction?

A
  • Acetylcholine (Ach) released into synaptic cleft
  • Ach attaches to Nicotinic Ach receptors (nAchR)
  • Acetylcholinesterase rapidly breaks down Ach in synaptic cleft
29
Q

What propagates an electrical signal from the motor endplate to the muscle?

A
  • Plasma membrane of muscle cells invaginates into muscle cell – transverse tubules that store Ca2+ (T tubules)
  • These are highly organised and penetrate muscle at 2 points in each sarcomere at junctions of I and A band
30
Q

How do transverse tubules in muscle propagate an electrical signal?

A
  • Along T tubule length is associated 2 cisternae of sarcoplasmic reticulum
  • Sarcoplasmic reticulum acts as storage organelle for [Ca2+]I
  • T tubule and 2 cisternae referred to as Triad
31
Q

Describe excitation-contraction coupling

A
  • Action potential from motor end plate propagates along skeletal muscle membrane and down T tubules
  • Depolarisation opens voltage gated L- type Ca2+ channels which are clustered in groups of 4 (tetrads)
  • Conformational change in DHP receptor activates Ca2+-release channel.
  • Increase in [Ca2+]I leads to activation of troponin C and cross-bridge cycling
32
Q

How is contraction of muscles terminated?

A
• Ca2+ must be removed from the cytoplasm for contraction to cease and relaxation to occur
• Minor
    – Na-Ca exchanger (NCX)
    – Ca pump at plasma membrane (PMCA)
• Major
    – Ca reuptake into SR by SERCA-type
Ca pump

So basically calcium is taken from the cytoplasm and stored in the sarcoplasmic reticulum

33
Q

What proteins store Ca in the sarcoplasmic reticulum and where are they found?

A
  • Calsequestrin and calreticulin are major Ca-binding proteins in skeletal muscle
  • Located predominantly at triad junction
34
Q

What defines the borders of a sarcomere?

A

The distance from one Z disc to another Z disc.

35
Q

What is the functional unit of skeletal muscle?

A

A sarcomere

36
Q

What gives myofibril a striated appearance?

A

The repeating sarcomere structure

37
Q

Describe the structure and origin of the thin filaments in a sarcomere?

A

There are an actin protein that originates at the Z band/disc and then grow out into the anisotropic (A) band

38
Q

What is the anisotropic band developed by in sarcomere structure?

A

The thick filament (myosin)

39
Q

What are the thick filaments attached to?

A

The M band

40
Q

Where can the M band be found in a sarcomere?

A

In the H band in the centre of the sarcomere

41
Q

What does the tropomyosin do on actin?

A

Prevents the action of myosin on actin

42
Q

How does calcium get from the sarcoplasmic reticulum to the myofibrils in skeletal muscle?

A

After an action potential propagates down transverse (T) tubules calcium is released by membrane channel proteins into T tubules at a triad (two SR cisternae + T tubule) which then enter the sarcomere at the junctions of the A and I bands

43
Q

What are L-type Ca2+ channels also called?

A

• L-type Ca2+ channel also called dihydropyridine (DHP) receptor as blocked by this class of antihypertensive drugs

44
Q

What is the Ca2+-release channel also called?

A

• Ca2+-release channel also called ryanodine receptor as blocked by plant alkaloids ryanodine and caffeine