14 - Skeletal Muscle Flashcards

1
Q

What is muscle? What are the different types?

A

One of the four “basic” tissues (nervous, epithelial, CT)

Skeletal, cardiac, and smooth - prefixes myo- and sacro-

Skeletal = voluntary

Cardiac and smooth = involuntary

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2
Q

What are skeletal muscle cells called? How big are they?

A

Aka fibers or myocytes

Largest cell - similar but not identical to cardiac myocytes. Have 100s of nuclei at cell periphery.

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3
Q

Describe the structure of skeletal muscle?

A

Highly structured, in a heirarchical fashion.

Gross muscle (cm) > fascicles (mm) > myocytes (10-100 microm) > myofibrils (~1 microm) > myofilament

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4
Q

Describe the epimysium, perimysium, and endomysium (CT investing in skeletal muscle).

A

Epimysium: deep fascia, invests the entire muscle

Perimysium: invests fascicles (groups of myocytes); continuous with CT at the myotendon junction

Endomysium: invests individual myocytes; adjacent to basal lamina.

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5
Q

What do you see on light microscopy of four adjacent myocytes?

A
  • Nuclei are peripheral
  • Striated: alternating A bands (dark) And I bands (light)
  • Z lines demarcate the sarcomere (unit of contraction)
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6
Q

Myocytes contain ______ that contain __________.

A

Myocytes contain myofibrils, that are adjacent to each other and aligned in register.

Each myofibril (~1 microm) is composed of thick and thin myofilaments (nm).

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7
Q

What are the different bands and zones seen in a myofibril?

A

I-band (light band) is bisected by the Z line.

A-band (dark band) is bisected by the H-zone/M line (contains MM-CK)

Sarcomeres (~2 microm long) reside between adjacent Z lines.

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8
Q

The ____ is the unit of striated muscle contrastion.

A

The sarcomere.

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9
Q

What are the two membranes of skeletal myocytes?

A

T (transverse) tubules: invaginate sarcolemma

SR (sarcoplasmic reticulum): envelops each myofibril

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10
Q

What is the structure of the presynaptic terminal, the cleft, and postsynaptic terminal of the NMJ?

A

Presynaptic: Ca2+ channels, synaptic vesicles (with ACh)

Cleft: AChE

Postsynaptic: junctional folds, AChRs facing cleft, Na+ channels in folds

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11
Q

What occurs at the neuromuscular (myoneural) junction?

A
  1. Nerve AP causes Ca2+ to enter the neuron.
  2. Synaptic vesicles fuse to pre-synaptic membrane and ACh is released into cleft
  3. ACh binds AChR on myocyte and Na+ enters the yocyte to cause a muscle AP.
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12
Q

What can block all steps at the NMJ that occur prior to Na+ enterings the myocyte to cause a msucle AP?

A

Succinylcholine or curariform drugs

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13
Q

What occurs during skeletal muscle excitation?

A

Depolarization in the T tubules causes calcium channel Cav 1.1 to be released.

Cav1.1 binds RyR (receptor) in the SR membrane, causing a huge efflux of Ca2+ from the sarcoplasmic reticulum into the cytoplasm.

Now the contraction phase can begin.

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14
Q

What occurs during skeletal muscle contraction?

A
  1. Ca2+ binds troponin C and tropomyosin moves out of the way.
  2. ATP > ADP + Pi and myosin binds actin
  3. Power stroke = contraction: thin filaments move into A-band and the sarcomere shortens
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15
Q

What moves to cause sarcomere shortening? What doesn’t change during contraction?

A

Thin filaments move.

During contraction: A-band is unchanged while I-band is shortened.

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16
Q

What occurs during skeletal muscle relaxation?

A

Ca2+ is pumped back into the SR via SERCA.

  • This requires phospholamban phosphorylation (phospholamban binding inhibits SERCA; when phosphorylated it dissociates from SERCA).
17
Q

What is rigor mortis?

A

In the absense of ATP, myosin stays bound to actin; therefore relaxation can’t occur, hence “stiffening” happens.

18
Q

What is malignant hyperthermia? What causes it?

A

Caused by giving volatile anesthetics to someone witha “gain of function” gene mutation:

  • CACNA1S gene (encodes Cav1.1)
  • RYR gene (encodes ryanodine receptor): RYR = Ca2+ channel in the SR that promotes Ca2+ release
19
Q

What is the intervention that can be done to treat malignant hyperthermia?

A

Dantrolene: muscle relaxant that inhibis Ca2+ release via RYR.

20
Q

How is muscle typing done? What does it tell us?

A

Each muscle has a characteristic ratio of fiber types.

“Typing” is done via immunochemistry and deviation from the usual ratio indicates muscle disease.

21
Q

What are type I skeletal muscle fibers? What substrate do they use?

A

slow twitch” fibers with continuous contraction (oxidative) - used by marathon runners.

  • Red due to myoglobin and mitchondria
  • generate ATP from aerobic respiration.
  • Substrate : fatty acids
22
Q

What are type II skeletal muscle fibers? What substrate do they use?

A

“fast twitch” fibers (glycolytic) - used by sprinters

  • White due to enrichment of glycogen
  • Generate ATP from anaerobic glycolysis
  • Substrate: glycogen
23
Q

How can skeletal muscles regenerate a whole muscle?

A

Via skeletal myoblasts aka “satellite cells

  • These are adult stem cells that reside in a “niche” between the sarcolemma (cell membrane) and basal lamina.
  • Activated from G0 after insult to basal lamina.
24
Q

Myofibrils are made up of myofilaments. Describe these.

A

Thick: A bands only (myosin)

Thin: I bands and A bands (actin, 3 troponins, and tropomyosin)

25
Q

What is each labeled aspect of this cross-section?

A

The perimysium surrounds the bundle of myocytes, which are each surrounded by endomysium.

The tiny red dots in each myocytes are the myofibrils.

26
Q

What is the ratio of thin to thick filaments in a myofibril?

A

Thin to thick is 6:1 (ie more small dots in the picture than large dots)

The sarcoplasmic reticulum is also present in this image.

27
Q

Other than ATP, energy for skeletal muscle fibers is also derived from ______ ______.

A

Creatine phosphate.

28
Q

Describe the regernation of skeletal muscle after injury/insult to the basal lamina on day 0.

A

Days 1-7: satelite cells (myoblasts) proliferate

Day 7: Myoblasts fuse together to form myotubes

Day 14: Many myotubes have formed and fused to each other and to original damaged myocyte; results in branching muscle cells with central nuclei (innervation begins)

Day 21: new skeletal muscle ell

29
Q

Why do you have diminished skeletal muscle regeneration ability at age 60+?

A

Because you have fewer satelite cells relative to fibroblasts.

30
Q

What is myostatin and what does it do?

A

A growth factor secreted by skeletal myocytes that inhibits satelite cell proliferation, likely via the upregulation of p21.

31
Q

What happens when you knock out the myostatin gene? When might this be important clinically?

A

Knocking out the myostatin gene causes skeletal muscle hypertrophy.

This could be a target for inhibition in muscular dystrophy patients.

32
Q

How common is duchenne muscular dystrophy? Who gets it and what is the cause?

A

1:3,500 males

Loss of dystrophin: 2.6 million bp (avg ~12,000 bp) with 79 exons.

Without dystrophin, the sarcolemma falls apart.

33
Q

What are some treatment options for duchenne MD?

A
  • Cellular therapy with skeletal myoblasts
  • Gene therapy with adenovirus-dystrophin cDNA
  • Drugs such as prednisone