14 - Skeletal Muscle

Question 1

What is muscle? What are the different types?

Answer 1

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

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

Skeletal = voluntary

Cardiac and smooth = involuntary

Question 2

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

Answer 2

Aka fibers or myocytes

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

Question 3

Describe the structure of skeletal muscle?

Answer 3

Highly structured, in a heirarchical fashion.

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

Question 4

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

Answer 4

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.

Question 5

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

Answer 5

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

Question 6

Myocytes contain ______ that contain __________.

Answer 6

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).

Question 7

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

Answer 7

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.

Question 8

The ____ is the unit of striated muscle contrastion.

Answer 8

The sarcomere.

Question 9

What are the two membranes of skeletal myocytes?

Answer 9

T (transverse) tubules: invaginate sarcolemma

SR (sarcoplasmic reticulum): envelops each myofibril

Question 10

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

Answer 10

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

Cleft: AChE

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

Question 11

What occurs at the neuromuscular (myoneural) junction?

Answer 11

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.

Question 12

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

Answer 12

Succinylcholine or curariform drugs

Question 13

What occurs during skeletal muscle excitation?

Answer 13

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.

Question 14

What occurs during skeletal muscle contraction?

Answer 14

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

Question 15

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

Answer 15

Thin filaments move.

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

Question 16

What occurs during skeletal muscle relaxation?

Answer 16

Ca2+ is pumped back into the SR via SERCA.

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

Question 17

What is rigor mortis?

Answer 17

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

Question 18

What is malignant hyperthermia? What causes it?

Answer 18

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

Question 19

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

Answer 19

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

Question 20

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

Answer 20

Each muscle has a characteristic ratio of fiber types.

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

Question 21

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

Answer 21

“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

Question 22

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

Answer 22

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

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

Question 23

How can skeletal muscles regenerate a whole muscle?

Answer 23

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.

Question 24

Myofibrils are made up of myofilaments. Describe these.

Answer 24

Thick: A bands only (myosin)

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

Question 25

What is each labeled aspect of this cross-section?

Answer 25

The **perimysium** surrounds the bundle of **myocytes,** which are each surrounded by **endomysium.** The tiny red dots in each myocytes are the **myofibrils**.

Question 26

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

Answer 26

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.

Question 27

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

Answer 27

Creatine phosphate.

Question 28

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

Answer 28

**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

Question 29

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

Answer 29

Because you have fewer satelite cells relative to fibroblasts.

Question 30

What is myostatin and what does it do?

Answer 30

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

Question 31

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

Answer 31

Knocking out the myostatin gene causes skeletal muscle hypertrophy. This could be a target for inhibition in muscular dystrophy patients.

Question 32

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

Answer 32

1:3,500 males Loss of ***dystrophin***: 2.6 million bp (avg ~12,000 bp) with 79 exons. Without dystrophin, the sarcolemma falls apart.

Question 33

What are some treatment options for duchenne MD?

Answer 33

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