Muscle Types
• SKELETAL MUSCLE
o Striated muscle
o Nuclei peripherally located
o Large cells, multinucleated
o Strong, quick discontinuous voluntary contraction
• CARDIAC MUSCLE
o Striated muscle
o Shorter/stubbier
cells than skeletal
muscle
o About twice as long
as they are wide
o Centrally located
nucleus (usually
single nucleus,
sometimes 2)
o Strong, continuous involuntary contraction
• SMOOTH MUSCLE
o Tapered, overlapping, non-striated
o Centrally located nucleus
o Weak, slow involuntary contraction
o Either continuous or discontinuous depending on the organSkeletal Muscle Packaging
• Skeletal muscle has to have packaging from outside to inside
• Bundles of MYOFIBRILS make up A MUSCLE FIBER, and bundles of muscle
fibers make up a MUSCLE
- Myofibrils are made up of organized filaments
- In muscle, the term FIBER is a CELL
Skeletal muscle connective tissue covering
- EPIMYSIUM: dense CT around muscle
- PERIMYSIUM: dense CT around fascicle
• ENDOMYSIUM: delicate CT around fiber
o Comes together at the ends of muscle cells and whole muscles to give rise to tendons
• There are blood vessels in the connective tissue – can see capillaries in
cross section located in the endomysium
• There are SATELLITE CELLS in the basement membrane (marked with Pax7)
o The younger you are, the more satellite cells
o Satellite cells play an important role in healing
Development of skeletal
muscle
- Myoblasts
- Satellite cells: source of stem cells in adult muscle that can repair damage
- Skeletal muscle cells grow by hypertrophy (cells get bigger) – not by hyperplasia (making more cells)
Molecular events
regulating muscle satellite cell activation during skeletal muscle
regeneration
• Quiescent satellite cells are seen in a resting myofiber (expressing Pax7, a
well-known MRF transcription factor expressed in quiescent satellite cells)
• Following damage, the myofiber, satellite cells are activated to enter the cell cycle and proliferate allowing for expansion of the myogenic cell
population
• These activated satellite cells are characterized by high expression of
MRFs, MyoD and Myf5
• The proliferative phase is followed by Myoblast terminal differentiation
and characterized by the upregulation of the MRF’s, Myogenin and Mrf4
• New myofiber formation (upon innervation)
Skeletal muscle
organization
• SARCOMERES: repeating
contractile units
- A band: anisotropic, dark band, composed of thick filaments, myosin
- I band: isotropic, light band, thin filaments, actin
- Z line: in the center of the I band, sarcomere is from Z line to Z line
- H zone: in the center of the A band
- M line: in the center of the H zone
THIN FILAMENTS of
Skeletal Muscle
- F-Actin: filaments of actin embedded in the Z line
- Tropomyosin: filamentous protein that fills the groove in F-actin and binds troponin
• Troponin:
o TnT: troponin subunit that binds tropomyosin
o TnC: troponin subunit that binds calcium
o TnI: troponin subunit that inhibits actin-myosin interaction
- Alpha-actinin: actin linking protein located at the Z line
- Desmin: intermediate filament located in muscle
TITIN
- Very large molecule that runs along myosin and binds to itself on the M line
- Gives some stress tolerance and stability
- Affects the overall flexibility of the muscle cell
- Keeps cells from being overstretched
- Has some recoil activity to set the structure of the cell
Sacroplasmic Reticulum
• Sarcoplasmic reticulum: special SER in muscle that sequesters and releases calcium
• Components:
o Terminal Cisternae: I band, calciquestrin
o Tubular Channels: A band
o H Sacs: H zone
o T-Tubules: penetrations of the cell membrane deep into the muscle cell cytoplasm
Myasthenia Gravis Clinical
Manifestations
- Inability to focus the eyes (extraocular muscular paresis)
- Drooping eyelids (ptosis) à levator palpebrae superioris; CN III
- Double vision (diplopia) à extraocular muslces; CN III, IV, VI
- Difficulty in chewing»_space; CN V
- Difficulty in swallowing (dysphagia)
- Slurring of words (dysarthria)
- Limb weakness (10%)
- Progressively worsens throughout the day
• Treatments:
o Cholinesterase Inhibitors
o Corticosteroids
o Immunosupressants
Muscular Dystrophy
• Predominantly affects young males
• Dystrophin gene is defective
o Large complex, located underneath cell membrane in skeletal
muscle
o ECM components = type IV collagen/laminin bind to series of
glycan molecules > bind to the sarcoglycan complex > bind to
dystrophin and host of internal molecules reinforce
cytoskeleton
o Function: reinforce muscle
membrane because skeletal muscle is under a lot of mechanical force
• Without dystrophin, mechanical
forces manipulate the
transmembrane binding molecules > rips a hole in the membrane >
hypercontraction of the muscle > cell death
• Muscle heals via satellite cells but
over time, you have fewer satellite
cells until they eventually deplete and most of your muscle cells get replaced by fat
- Few remaining muscle cells are huge in diameter compared to normal because they’re hypertrophying to compensate for lack of satellite cells
- Eventually can no longer replace muscles in the diaphragm so they can’t breathe anymore – patients usually die young
Cardiac Muscle
- MYOCYTES: muscle cells
- CYTOPLASM: full of organelles, myofibrils
- STRIATIONS: not as distinct as in skeletal muscle
- NUCLEI: centrally located
- MYOFIBRILS: not as uniformly distributed as skeletal muscle
- MITOCHONDRIA: abundant and interspersed in cytoplasm
- BRANCHING and ANASTOMOSING fibers
- SARCOPLASMIC RETICULUM: less defined than in skeletal muscle
- INTERCALATED DISCS: at sarcomere ends, connect myocytes
- PURKINJE FIBERS: close to endocardium, specialized cardiac muscle cells
- Heart Impulse Conduction System
• MYOENDOCRINE CELLS: cardiodilatins (CDD) or atrial natriutetic
polypeptides
- vasodilation
Integrin
- Col I and II binds near the Z line to individual muscle cells
- Integrins bind the collagen
• Beta chains that pass through the cell
membrane and bind to the small cytoplasmic domain
• Bind to a host of molecules underneath
the cell membrane
• Dystrophin doesn’t exist in the heart, instead it has integrin + vinculin complex which has a similar adhesion function
Intercalated Disc
• On the vertical portions: has FACIAE ADHERENS – similar to zonula adherens found in cell junctions
• The whole end of the cell where the sarcomere is binds through the faciae
adherens to the end of the next cell
• On the horizontal portions, there are gap junctions
Conduction system
- AV bundle of His penetrates cardiac skeleton
* Purkinje fibers – bigger muscle cells that spread excitations quickly
Smooth Muscle
- LOCATION: tubular organs
- FORM: spindle shaped
- SIMILAR CELLS: myoepithelial cells, pericytes
- LIGHT microscope structure: elongated, nonstriated, overlapping
- THIN FILAMENTS: 30-80 A, composed of actin
• DARK PATCHES: cytoplasmic dense bodies,
sub plasmalemma dense
plaques
• ANCHORING FILAMENTS: 100A, desmin intermediate filaments, links
together bodies and plaques
- THICK FILAMENTS: 120-160 A, composed of myosin
- SLIDING filament mechanism: calmodulin dependent
