14 - Skeletal Muscle Flashcards
What is muscle? What are the different types?
One of the four “basic” tissues (nervous, epithelial, CT)
Skeletal, cardiac, and smooth - prefixes myo- and sacro-
Skeletal = voluntary
Cardiac and smooth = involuntary
What are skeletal muscle cells called? How big are they?
Aka fibers or myocytes
Largest cell - similar but not identical to cardiac myocytes. Have 100s of nuclei at cell periphery.
Describe the structure of skeletal muscle?
Highly structured, in a heirarchical fashion.
Gross muscle (cm) > fascicles (mm) > myocytes (10-100 microm) > myofibrils (~1 microm) > myofilament
Describe the epimysium, perimysium, and endomysium (CT investing in skeletal muscle).
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.
What do you see on light microscopy of four adjacent myocytes?
- Nuclei are peripheral
- Striated: alternating A bands (dark) And I bands (light)
- Z lines demarcate the sarcomere (unit of contraction)
Myocytes contain ______ that contain __________.
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).
What are the different bands and zones seen in a myofibril?
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.
The ____ is the unit of striated muscle contrastion.
The sarcomere.
What are the two membranes of skeletal myocytes?
T (transverse) tubules: invaginate sarcolemma
SR (sarcoplasmic reticulum): envelops each myofibril
What is the structure of the presynaptic terminal, the cleft, and postsynaptic terminal of the NMJ?
Presynaptic: Ca2+ channels, synaptic vesicles (with ACh)
Cleft: AChE
Postsynaptic: junctional folds, AChRs facing cleft, Na+ channels in folds
What occurs at the neuromuscular (myoneural) junction?
- Nerve AP causes Ca2+ to enter the neuron.
- Synaptic vesicles fuse to pre-synaptic membrane and ACh is released into cleft
- ACh binds AChR on myocyte and Na+ enters the yocyte to cause a muscle AP.
What can block all steps at the NMJ that occur prior to Na+ enterings the myocyte to cause a msucle AP?
Succinylcholine or curariform drugs
What occurs during skeletal muscle excitation?
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.
What occurs during skeletal muscle contraction?
- Ca2+ binds troponin C and tropomyosin moves out of the way.
- ATP > ADP + Pi and myosin binds actin
- Power stroke = contraction: thin filaments move into A-band and the sarcomere shortens
What moves to cause sarcomere shortening? What doesn’t change during contraction?
Thin filaments move.
During contraction: A-band is unchanged while I-band is shortened.
What occurs during skeletal muscle relaxation?
Ca2+ is pumped back into the SR via SERCA.
- This requires phospholamban phosphorylation (phospholamban binding inhibits SERCA; when phosphorylated it dissociates from SERCA).
What is rigor mortis?
In the absense of ATP, myosin stays bound to actin; therefore relaxation can’t occur, hence “stiffening” happens.
What is malignant hyperthermia? What causes it?
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
What is the intervention that can be done to treat malignant hyperthermia?
Dantrolene: muscle relaxant that inhibis Ca2+ release via RYR.
How is muscle typing done? What does it tell us?
Each muscle has a characteristic ratio of fiber types.
“Typing” is done via immunochemistry and deviation from the usual ratio indicates muscle disease.
What are type I skeletal muscle fibers? What substrate do they use?
“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
What are type II skeletal muscle fibers? What substrate do they use?
“fast twitch” fibers (glycolytic) - used by sprinters
- White due to enrichment of glycogen
- Generate ATP from anaerobic glycolysis
- Substrate: glycogen
How can skeletal muscles regenerate a whole muscle?
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.
Myofibrils are made up of myofilaments. Describe these.
Thick: A bands only (myosin)
Thin: I bands and A bands (actin, 3 troponins, and tropomyosin)
What is each labeled aspect of this cross-section?
The perimysium surrounds the bundle of myocytes, which are each surrounded by endomysium.
The tiny red dots in each myocytes are the myofibrils.
What is the ratio of thin to thick filaments in a myofibril?
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.
Other than ATP, energy for skeletal muscle fibers is also derived from ______ ______.
Creatine phosphate.
Describe the regernation of skeletal muscle after injury/insult to the basal lamina on day 0.
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
Why do you have diminished skeletal muscle regeneration ability at age 60+?
Because you have fewer satelite cells relative to fibroblasts.
What is myostatin and what does it do?
A growth factor secreted by skeletal myocytes that inhibits satelite cell proliferation, likely via the upregulation of p21.
What happens when you knock out the myostatin gene? When might this be important clinically?
Knocking out the myostatin gene causes skeletal muscle hypertrophy.
This could be a target for inhibition in muscular dystrophy patients.
How common is duchenne muscular dystrophy? Who gets it and what is the cause?
1:3,500 males
Loss of dystrophin: 2.6 million bp (avg ~12,000 bp) with 79 exons.
Without dystrophin, the sarcolemma falls apart.
What are some treatment options for duchenne MD?
- Cellular therapy with skeletal myoblasts
- Gene therapy with adenovirus-dystrophin cDNA
- Drugs such as prednisone
