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Histology of Skeletal Muscle-Michaely

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xibocutie's version from 2017-01-17 02:27

Thin Filament of Sarcomere

Question Answer
Short actin filamentcore of thin filament
Capping proteinsCapZ and tropomodulin cap the (+) and (-) ends of actin
CapZ and tropomodulinCapping proteins on Thin Filament
Tropomyosinstabilizes actin filament and blocks myosin binding to actin
Troponina complex of three subunits (I, T and C). In response to cytosolic calcium, troponin moves tropomyosin out of the way so that myosins in the thick filament can bind and pull on actin.
In response to Ca, which structure moves tropomysosin out of the way to allow myosin to bind and pull on actin?Troponin
Nebulinspecifies length of actin filament
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Thick filament of Sarcomere

Question Answer
Type II myosinATPase that pulls on thin filament. Has 4 domains
Head Domain of Type II myosinmotor domain. Binds actin. Hydrolyzes ATP.
Neck Domain of Type II myosindefines step size for motor domain.
Coiled-coil domain of Type II myosinpolymerizes myosin into the thick filament.
C-terminal domain of Type II myosinBinds Titin
Myosin binding protein CStructure organizer for thick filament. It associates with titin and myosin to specify thick filament length. Promotes generation of bipolar filaments with a central bare zone (lacking myosin heads)
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Z-line Composition of Sarcomere

Question Answer
alpha-actininprovides elastic crosslinks between opposing thin filaments
Desminmuscle-specific intermediate filament protein. Desmin filaments bind to adaptor proteins (plectins) that associate with the Z-line, costameres, nuclei and mitochondria. These linkages align Z-lines of adjacent myofibrils and insure that the cellular components of the myofiber move in unison during contractions.
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M-line Composition of Sarcomere

Question Answer
What connects thick filaments at M-line?Composition of fibers that connect thick filaments has not yet been established
Myomesincrosslinks titin to myosin at M-line
What occurs at M-line?Site of Energy production/consumption regulators
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Titin

Question Answer
What is Considered to be the third filament system of skeletal muscle?Titin
What extends from Z-line to M-line?Titin
Titin serves what purpose?serves as a bungee cord that keeps the sarcomere together after myosin releases actin during relaxation
What determines the lenght of thick filament?Titin
Where does titin bind on the thick filament?Binds to the surface of the thick filament-templates the lenght of this filament
Where does titin bind on the thin filament?Near Z line
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Structures involved in force transmission--Costameres

Question Answer
Costameressite where Z-lines transmit force to the external lamina
Dystroglycan complexa. Bind to laminins in the external lamina
b. Binds to dystrophin, which binds to thin filaments at Z-line
c. Binds to ankyrin, which binds to titin
d. Ankyrin also binds to plectin, which binds to desmin
What does dystropin bind to?Binds to thin filaments on Z line
What does ankyrin bind to?Binds to desmin
What does plectin bind to?Binds to desmin
Integrin/vinculin/talin complexa. Binds to laminins and collagens in the external lamina
b. Binds via alpha-actinin to actin in membrane skeleton, this actin is linked to thin filaments at the Z-line by alpha-actinin
Dystroglycan complex binds to what 3 things?Laminin, dystrophin, and ankyrin
What does the integrin/vinculin/talin complex bind to?Laminins and collagens and actin (via alpha-actin)
What two things make up a costamere?dystroglycan complex and Integrin/vinculin/talin complex
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Structures involved in force transmission--Myotendinous junction

Question Answer
Myotendinous junction (MTJ) -transmission of force to tendon and bone
Structure of tendonRegular dense connective tissue, tenocytes (fibroblasts), and some innervation
Tendon fibroblaststenocytes
What is the function of tenocytes?Maintain connective tissue
Structure of muscle at the MTJa. Thin filaments provide core of microvilli-like structures that are surrounded by collagen fibers of the tendon
b. Extensive desmin linkages between thin filaments and integrins in MTJ
c. Integrins bind to external lamina
d. External lamina binds to collagen in tendon
e. Architecture makes most linkages orthogonal to force on junction (thus making the linkage much stronger than an end-on-end linkage)
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Structures involved in excitation-contraction coupling--Motor Unit

Question Answer
Skeletal muscles are stimulated by what kind of neurons?By alpha-motor neurons
Each muscle fiber is innervated by exactly how many alpha neurons?1
T/F Each alpha-neuron can innervate multiple muscle fibers?true
What is a motor unit?The combination of one alpha-motor neuron and its innervated myofiber makes up a motor unit.
What dictates muscle contraction strenght?Motor unit strenght x #of motor units activated
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Structures involved in excitation-contraction coupling--Neuromuscular Junction

Question Answer
What component make up the neuromuscular junction on the neuronal side?a. Axon terminal
b. Synaptic vesicles: hold neurotransmitter (acetylcholine)
c. Presynaptic membrane: site of synaptic vesicle fusion; faces sarcolemma
d. Schwann cell: insulates junction and prevents leakage of acetylcholine
What is the motor end plate?The muscle side of NMJ junction
What are the components of the motor end plate?two. Junctional folds: folds in motor end plate b. External lamina: covers sarcolemma and fills the synaptic cleft separating the presynaptic membrane from the motor end plate. Binds to acetylcholinesterase
What are the steps of excitation at the NMJ?a. Nerve depolarization  fusion of pre-bound synaptic vesicles with the presynaptic membrane
b. Synaptic vesicle fusion release of acetylcholine into the synaptic cleft
c. The external lamina of the muscle fiber binds acetylcholinesterase, an enzyme that degrades acetylcholine. This enzyme normally keeps the synaptic cleft free of acetylcholine; however, the bolus of acetylcholine that is released by stimulated synaptic vesicle fusion overwhelms this enzyme, resulting in acetylcholine reaching the surface of the motor end plate.
d. Acetylcholine binding to acetylcholine receptors on tips of junctional folds  Activation of non-selective cation channel activity of these receptors.
e. Depolarization of junctional folds by acetylcholine receptors  Activation of voltage-gated sodium channels at the base of the folds (most abundant at the periphery of the motor end plate).
f. Propagation of depolarization wave (action potential) across sarcolemma.
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T-tubules

Question Answer
What are T-tubules?Invaginations of the sarcolemma that penetrate down to and wrap around myofibrils
What are terminal cisterna?specialized region of the sarcoplastic reticulum associated with t-tubules
What makes a triad?One T-tubule + 2 terminal cisternae
Terminal cisternae have a high concentration of what protein?Calsequestrin
What does calsequestrin do?Buffers calcium in the terminal cisternae
Where can triads be found?Positioned at the I-band/A-band transition zone
How is transduction of T-tubule depolarization to calcium release from SR occur?1. Action potential along sarcolemma passes down t-tubules to myofibrils. 2. Depol in T-tubules activates DHPR, which are bound to RyR on terminal cisternae. DHPR are Ca channels, however, the Ca release by these receptors is not needed and doesn't cause Ca entry into skeletal myofibers. 3. The impt mechanism is this: the voltage-dependent conformational in DHPR receptors causes a compensatory change in the bound RyRs that then gates the Ca channel activity of RyR. Opening of the RyRs (also called gating) releases Ca from SR into cytosol. DHPR overall acts as the VOLTAGE SENSOR and RyR as the CALCIUM RELEASE CHANNEL.
In a triad, who acts as the voltage sensor?The Dihydropyridine receptor
In a triad, who acts as the calcium release channel?RyR (Ryadonine receptor)
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Mechanism of Ca-triggered contraction

Question Answer
First step, Ca binds to what subunit of troponin?Binds to C subunit of troponin (TnC)
What happens after Ca binds to C subunit of troponin (2nd step)?A conformation change in troponin complex
Once a conformational change occurs of troponin complex, what happens next (third step)?Shift in tropomyosin from myosin-binding site on actin. Then Myosin is able to bind to actin.
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Relaxation of Muscle

Question Answer
What pumps Ca from cytosol back into SR?Ca-ATPases constantly pump Ca from cytosol back into SR
How does DHPR/RyR-mediated Ca release stop?Once excitation is absent
Cessation of calcium release causes rapid what?rapid loss of cytosolic Ca (due to to Ca-ATPases)
What allows tropomyosin to go back to occlude myosin-binding sites on actin?Loss of Ca. Thus, Myosin releases from actin and sarcomeres expand.
What limits extension of sarcomeres to a specified lenght?Titin. acts as a bungee rope
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Know page 263 in syllabus