Skeletal Muscle (voluntary!!

):

• Several cell types:

○ Skeletal Myocytes
○ Endothelia cells- vascular cells that nourish skeletal myocyte
○ Fibroblasts (connective tissue)
• Hierarchy of structure (large to small):
○ Muscle (cm)fascicle (mm)skeletal myocyte (10-100Microm)
myofibril (1-2microm)myofilament (nm)
○ Multinucleated (hundreds of nuclei in each cell)
○ Striated
• Layers of connective tissue (continuous)
○ Epimysium—outside layer of muscle
○ Perimysium—surrounds fascicles
○ Endomysium—surrounds fiber or skeletal myocyte
 Continuous with basal lamina—present in all muscle cells
○ CT investments are continuous
 CT at ends of muscles is continuous with the CT of tendons that
attach the muscle to bone
• Example: CT at myotendon jxn is continuous with the
dense regular CT connecting the muscle to bone.
• Skeletal Muscle in Longitudinal Section:
○ Striations and peripheral nuclei
○ I band: light—only thin myofilaments, bisected by Z band
 Thin Myofilaments: actin, troponin, and tropomyosin
 Alpha actinin: anchors actin filaments at the Z disc
 Troponin-prevents myosin interaction with actin in the absence
of Ca++
 Tropomyosin: binds along the length of actin filaments; involved
in Ca++ regulation.
○ A band: Dark (bisected by light H-zone)
 Contains both thin and thick myofilaments
○ H-zone bisected by M-line
○ M-line: contains MM-creatine kinase
○ **Sarcomere: area b/w successive z-lines, 2 micrometers long**
 Fundamental unit of muscle contraction
○ 6 thin myofilaments surround one thick myofilament!
• Membranes in striated muscle:
○ Transverse Tubule
 Adjacent to A-I jxn
 Invaginate from sarcolemma to carry depolarization waves deep
into cell
○ Sarcoplasmic Reticulum
  Envelops each myofibril
 Abuts the transverse tubule, but does not intersect it.
 All smooth muscle
 Reservoir for Calcium
○ Triad:
 Two SR membranes on either side of a t-tubule membrane
 Occurs at A-I junction
• Contraction via excitation coupling:
○ Excitation phase:
 Depolarization wave traverses Sarcolemma and travels into T-
tubulesT-tubule depolarized SRSR releases CA++, increasing
CA++ concentration in the myfibrils
○ Contraction phase:
 CA++ binds troponin-c, causing it to shift and expose the
myosin binding sites (on the actin)Actin binds myosin head
ATP on myosin head is hydrolyzed..providing energy for power-
stroke in which the thin filaments are pulled in the A-band.
 End result of contraction: sarcomere shortens
• Relaxation of Striated Muscle:
○ Ca++ is pumped back into SR
 ATP dependent
○ Troponin C shifts and covers myosin binding site
○ ATP binds myosin allowing its release from actin
○ Rigor Mortis- inability to relax muscles due to absence of ATP.
○ Malignant Hyperthermia-SR can’t re-sequester CA++ resulting in
sustained muscle contraction
 Increases body temperature
 Life threatening
 Inherited
 Occurs under anesthesia
• Skeletal Muscle in Cross Section:
○ Myofibrils appear as red dots in the sarcoplasm of each skeletal
myocyte
○ Striations not apparent
• EM Level:
○ Myofibril surrounded by SR membrane
○ Six thin filaments surround each think filament
• Energy Production:
○ ATP, creatine phosphate, glycogen and fatty acids
 Sprinters: use glycogen
 Marathoners: use fatty acids
• Muscle Types:
○ Can be identified using immunohistochemistry
 Ex. monoclonal antibody stains
○ Type I:
 Continuous contraction
 Slow twitch
 Red
 Enriched in Mitochondria and myoglobin
• Used for fatty acid oxidation and oxidative metabolism
○ Type II:
 Rapid, discontinuous contraction
 Fast Twitch
 White (less myoglobin)
 IIA, IIB and IIC
 Glycolytic or mixed oxidative/glycolytic
○ Skeletal Muscle Regeneration
 Via adult stem cells
• Mononuclear
• Resides in niche:
○ b/w sarcolemma and the basal lamina of the
skeletal myocyte
• AKA Satellite Cells (although not entirely correct)
• Resting in G0 phase of the cell-cycle in normal tissue
• When basal lamina is damagedreleases growth factor
that induces underlying satellite cells to re-enter the cell
cycle in G1.
• Following multiplication, the cells irreversibly withdraw
from the cell-cycle and fuse togetherform multinuclear
muscle cells
○ AKA myotubes
 Undergo robust muscle differentiation
 Can regenerate entire muscles
○ Clinical value of satellite cells/myoblasts:
 Cardiac Insufficiency
• Researchers have harvested and injected muscle myo-
satelite cells into the heart.
• Modest improvement in injection fraction
 **Duchene Muscular Dystrophy**
• Mutation in gene encoding dystrophin
○ Sub-sarcolemmal protein that participates in a
complex to stabilize the myocyte cytoskeleton
○ Without dystrophin, the sarcolemma breaks down
and muscle cell dies.
○ Enormous gene (97 exons spread along 2.6 million
bp)
○ Mutations introduce premature stop signals for
transcription
○ X-linked
○ Interventions in the pipeline:
 Cellular therapy using myo-satellite cells
 Gene therapy (introducing dystrophin genes
into skeletal myocytes
 Drugs that circumvent unscheduled stop
signals in the mutated gene.