Skeletal muscle

Question 1

Skeletal muscle cells

Answer 1

voluntary

aka fibers, myocytes, large

highly structured, in hierarchial fashion
Gross muscle–> fascicles–> myocytes–> myofibrils–>myofillaments

Nuclei at the cell periphery (central location denotes pathology)

Question 2

Connective tissue investing skeletal muscle

Answer 2

Epimysium (deep fascia)- invests the entire muscle

Perimysium- invests fascicles, which are groups of myocytes, continuous with CT at the my tendon junction

Endomysium- invests individual myocytes, adjacent to their basement membrane aka basal lamina

Question 3

Light microscopy longitudinal

Answer 3

Nuclei (myonuclei) are peripheral, striated
Alternating A bands (dark), and I bands (light)

Z lines demarcate the sarcomere=unit of contraction

electromicroscope: myocytes are composed of myofibrils

Myofibrils lie parallel to each other, aligned in register
I band (light band) is bisected by z line
A band (dark band) bisected by H zone and M line (contains MM CK)

Sarcomere( zline to z line)
Unit of striated muscle contraction

Question 4

myofilaments

Answer 4

myofibrils contain myofilaments

Thick- are only in the A band contain myosin

Thin: in I and A band: actin, 3 troponins, tropomyosin

Question 5

Membranes of skeletal myocytes

Answer 5

T (transverse) tubules invaginate the sarcolemma

Sarcoplasmic reticulum envelops each myofibril

The triad: 2 SR and 1 T tuble

Question 6

Neuromuscular Myoneural Junction

Answer 6

Structure:
Pre synaptic: Ca++ channels, synaptic vesicle (with Ach)
Cleft: AChE
Post synaptic: junctional folds, AchR s facing the cleft, Na+ channels deep in folds

Function: Nerve Ap–> Ca++ enters the neuron, synaptic vesicles fuse to the pre synaptic membrane. ACh is released into the synaptic cleft

ACh binds ACh Rs on the sarcolemma

Na enters myocyte–>muscle AP

Question 7

Skeletal muscle component of NMJ

Answer 7

Excitation (electrical): Sarcolemma depolarizes–> T-tubules–>Cav1.1

Cav1.1 binds RyR in SR membrane–> Ca++ release from SR

Contraction: Ca++ binds troponin C–> tropomyosin moves out of the way

ATP–>ADP Pi myosin binds actin

Power stroke=contraction: thin filaments move into the A band, sarcomere shortens

Question 8

Contraction filaments

Answer 8

Thin filaments move= sarcomere shortening

Duration of contraction (length of A band stays the same), length of I band shortened)

Relaxation: Ca++ is pumped back into SR via SERCA. Requires Phospholaman to be phosphorylation

Phospholamban binds to and inhibits SERCA, when phosphorylated it dissociates from the SERCA

Rigor mortis: no ATP myosin stays bound to actin, therefore relaxation can’t occur and stiffening happens

Question 9

Malignant hyperthermia

Answer 9

caused by volatile anesthetics
Gain of function mutations in the CACNA1S gene (encodes CAv1.1)

RYR gene encodes ryandodine recetor

intervention: dantrolene, muscle relaxant, inhibits Ca++ release via RYR

Question 10

Cross sectional orientation of muscle

Answer 10

Light microscope: Fascilce
perimysium–> endomysium, can see myofibrils, and no striations

EM: myofibrils (thin to thick 6:1)
you can see the sarcoplasmic reticulum

Question 11

energy for muscle contraction

Answer 11

Muscle fiber types:

Each muscle in the body has a characteristic ration of fiber types. fiber typing is immunohistochemistry

Deviation from usual ratio indicatates muscle disease

Type 1: slow twitch continuous contraction (oxidative): Red fibers due to enrinchment of myoglobin and mitochondria,
generate ATP from aerobic respiration
Substrate: Fatty acids
used by marathoners

Type 2 (with subtypes A B and C) fast twitch: glycolytic, white fibers due to enrichment of glycogen. Generates ATP from anaerobic glycolysis, Substrate : glycogen
Used by sprinters

Energy is also derived from creatinine phosphate

Question 12

Can skeletal muscle regenerate

Answer 12

yes!
Skeletal myoblasts aka satellite cells

Satellite cells are adult stem cells

Reside in a nich v sarcolemma and basal lamina

Activated from G0 after insult to basal lamina

Question 13

Regeneration of skeletal muscle days

Answer 13

Day0: injury/insult to basal lamina
Days 1-7: satellite cells (myoblasts) proliferate (compete with invading fibroblasts–scar)

Day 7: Myoblasts fuse together to form myotubes

Day 14: many myotubes have formed (fused to each other and to original damaged myocyte, result: branching muscle cells with central nuclei, innervation begins

Day 21: new skeletal muscle cells

By age 60 less satellite cells resulting in diminished regeneratve potential

Question 14

Myostatin

Answer 14

Growth factor secreted by skeletal myocytes

inhibits satellite cell proliferation: likely via up regulation of p21

KO of myostatin gene–> skeletal muscle hypertrophy

Target for inhibition in muscular dystrophy pt

Question 15

Duchenne muscular dystrophy

Answer 15

1 in 3500 males

Dystrophin largest gene :

Treatments: cellular therapy with skeletal myoblasts
Gene therapy with adenovirus-dystrophin cDNA
Drugs Prednisone