Sarcomere Structure Flashcards
What is the structure of striated muscle?
• 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)
Discuss muscle development
- 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
Discuss the structure of sarcomere
- 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
What contractile proteins are present in sarcomeres?
• 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
What are the structural proteins of sarcomere?
- α-actinin
- Titin
- Nebulin
- Dystrophin
What role does α-actinin play in sarcomere?
– Part of spectrin family of actin-binding proteins
– Binds end of thin filaments to Z discs
What role does titin play in sarcomere?
– 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
What role does nebulin play in sarcomere?
– 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
What role does dystrophin play in sarcomere?
– Large protein associated with Z disks
– Helps align Z disks with disks in adjacent myofibrils
What is present in the I band of a sarcomere?
thin filaments only
What is present in the H zone of a sarcomere?
thick filaments only
What is present in the M line of a sarcomere?
thick filaments linked with accessory proteins
What is present in the outer edge of the A band of a sarcomere?
thick and thin filaments overlap
What are thin filaments in sarcomere made of?
• Thin filaments consist of 3 proteins
– Actin
– Tropomyosin
– Troponin
What is the structure of thin filaments in sarcomere?
- 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
What is tropomyosin?
– Regulatory protein
– Overlaps binding sites on actin for myosin and inhibits interaction when in the relaxed state
What is troponin?
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
What does Ca2+ binding to troponin do?
regulates skeletal muscle contraction because it moves the tropomyosin away and allows myosin to interact with the actin
What are thick filaments in sarcomere?
• Thick filaments are bipolar assemblies of multiple myosin-II molecules
What is myosin-II made of?
• 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
How does Ca2+ modulate contraction?
through regulatory proteins rather than direct interaction with contractile proteins
What occurs to regulatory proteins in cross bridge cycling without Ca2+?
regulatory proteins act to inhibit actin-myosin interactions
What role does troponin C play in the initiation of cross bridge cycling?
• 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)
Describe the initiation of cross bridge cycling
- 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
What areas of the sarcomere move during contraction?
Both the H zone and I band shorten
What first initiates contraction of muscle?
cerebral cortex which acts via α-motor neurons
What occurs to motor neurons in the neuromuscular junction?
Motor neurons flattened to form motor endplate
What neurotransmitters are used at the motor endplate in contraction?
- Acetylcholine (Ach) released into synaptic cleft
- Ach attaches to Nicotinic Ach receptors (nAchR)
- Acetylcholinesterase rapidly breaks down Ach in synaptic cleft
What propagates an electrical signal from the motor endplate to the muscle?
- 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
How do transverse tubules in muscle propagate an electrical signal?
- 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
Describe excitation-contraction coupling
- 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
How is contraction of muscles terminated?
• 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
What proteins store Ca in the sarcoplasmic reticulum and where are they found?
- Calsequestrin and calreticulin are major Ca-binding proteins in skeletal muscle
- Located predominantly at triad junction
What defines the borders of a sarcomere?
The distance from one Z disc to another Z disc.
What is the functional unit of skeletal muscle?
A sarcomere
What gives myofibril a striated appearance?
The repeating sarcomere structure
Describe the structure and origin of the thin filaments in a sarcomere?
There are an actin protein that originates at the Z band/disc and then grow out into the anisotropic (A) band
What is the anisotropic band developed by in sarcomere structure?
The thick filament (myosin)
What are the thick filaments attached to?
The M band
Where can the M band be found in a sarcomere?
In the H band in the centre of the sarcomere
What does the tropomyosin do on actin?
Prevents the action of myosin on actin
How does calcium get from the sarcoplasmic reticulum to the myofibrils in skeletal muscle?
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
What are L-type Ca2+ channels also called?
• L-type Ca2+ channel also called dihydropyridine (DHP) receptor as blocked by this class of antihypertensive drugs
What is the Ca2+-release channel also called?
• Ca2+-release channel also called ryanodine receptor as blocked by plant alkaloids ryanodine and caffeine
