Muscle

Question 1

Explain the organization of muscle components and their ensheathment

Answer 1

1. Epimyseium (dense irregular CT) surrounds the entire muscle
2. Perimyseium is partitions of dense irrecular CT from the epimyseuim, which divides the muscle into fasicles or bundles.
3. Endomyseium, is loose CT surrounding each muscle cell/fiber, and it contains the supplying cappilaries and nerves

Question 2

Explain the makeup of skeletal muscle.

Answer 2

1. Epimyseium/Perimyseium/Endomyseium sheaths
2. Muscle fibers is composed of a sarcolemma (plasma membrane) and sarcoplasm (composed predominantly by myofibrils)
3. Myofibrils contain the repeating sequences of the sarcomeres, which functional unit of muscle fibers.
4. The sarcomere is composed of thick (myosin - 250 molecules) and thin (actin) filaments, borded by the Z-line (made up of alpha-actinin). They are cylidrical, with each thick filament surrounded by 6 thin filaments (in A-band), and altogether there are 2 thin filaments per 1 thick filament.

Note: the nuclei of the muscle fiber is at the periphery, and it is multinucleated

Question 3

Explain the composition of the different lines/bands of the sarcomere.

Answer 3

Z-line is at the edges of sarcomere and is composed of alpha-actinin which binds the plus end of actin filament

I-band is the area where only thin, actin, filaments (light on EM) is located

A-band is the entire thick, myosin, filament region, which includes areas with overlapping thin-thick filaments.

H-zone is the area where only thick filaments populate.

M-line is the area of the H-zone, where there is no globular myosin heads (bare region).

Question 4

During contraction, explain the change in bands/zones in sarcomere.

Answer 4

The I-band and H-zone shorten, due to greater overlap of actin & myosin filaments.

The A-band does not change, because it includes the overlapping areas already.

Question 5

Explain the components of AP conduction in muscle fibers.

Answer 5

1. T-tubules, which are invaginations of the sarcolemma, and the area that AP is conducted along.
2. Sarcoplasmic Reticulum (SR), is a modified smooth ER that houses calcium and responds to electrical stimulus.
3. Termina cisternae is a branch of the SR that connects to T-tubules (feeling the stimulus)
4. Triad (in skeletal muscle) is seen as a T-tubule and two terminae cisternae connected to a SR.

Question 6

What are some features of cardiac muscle?

Answer 6

1. Striated
2. Short, cyllindrical, branched (compared to parallel sk muscle fibers)
3. Branches are joined by intercalating disks (consists of desmosomes, gap junctions, and fascia/zona adherins)
4. Large T-tubules, which is the site of calcium influx, with a small SR - forming a diad, not triad.

Question 7

What are some features smooth muscle?

Answer 7

1. Not striated (no myofibrils, still have thick and thin)
2. Spindle shaped, central nucleus
3. Secrete ECM molecules
4. Myosin heads must be phosphorylated for contraction and unidirectional
5. Actin inserts into alpha-actinin in dense bodies forming the anastomosing array (net encompassing cell)
6. SR is present but very underdeveloped, and there are no T-tubules at all.
7. Many vesicles under sarcolemma.

Question 8

What is the process of smooth muscle contraction?

Answer 8

• Signal passes through gap junction, which electrically stimulates sarcolemma.
• Calcium levels increase causing phosphorylation of myosin
• Contraction occurs, which leads to cell shortening and nuclei become passively pleated.

Question 9

The arrangment of skeletal myofilaments is directed by what proteins?

Answer 9

• Alpha-actinin is responsible for anchoring actin to the z-line (dense bodies in anastomosing array for smooth muscle).
• Myomesin is responsible for anchoring myosin’s bare region to the M-line.
• Titin extends from Z-line to M-line to help anchor the thick/myosin filaments (it provides elasticity for sarcomeres).

Question 10

What regulates the growth, nucleation, regeneration of muscle fibers?

Answer 10

• The growth of myofibrils and sarcomeneres are very uniform, because whenever the diameter of a myofibril gets too large, the calcium diffuion rate limits it and the myofibril splits into two seperate myofibrils. They get longer by adding sarcomeres to the ends.
• Myofibrils (skeletal) are multinucleate because myoblasts fuse together and lose their ability to divide.
• Satellite cells have some limited reginerative capacity and are present under the basal lamina.

Question 12

Describe muscular dystrophy, possible therapies, and specifically note Duchenne’s & Becker’s MD.

Answer 12

Actin is linked by dystrophin to dystroglycan complex (connected to basal lamina via laminin). Frameshift mutation of the dystrophin gene leads to Duchenne’s MD (DMD). The dystrophin gene is huge, composed of 79 exons, and mutations in the 44th-53rd exons are especially dangerous. Specifially, exon 51 is 13% of all of the DMD cases. For DMD, there is exon skipping thereapies in clinical trials (drisapersen and eteplirsen). Becker’s MD is larger deletions, but still produces a functional protein, because the reading frame is unaffected.

Other forms of MD can be seen when mutations in dystroglycan or sarcoglycan genes occur.

Question 13

Explain the regenerative capacity for cardiac and smooth muscle.

Answer 13

• Cardiac has extremely limited capacity because it lacks satellite cells, therefore damage causes fibroblasts to form connective scar tissue. New evidence of small number of stem cells in heart, and stem cell therapy (either mesenchymal - BM or induced pluripotent stem cells) is promising
• Smooth muscle retains ability to proliferate and increase size. In response to injury, smooth muscle cells proliferate and get larger (perfect example is uterus during pregnancy). No satallite cells are present.