Term
| What is the location of skeletal muscle? |
|
Definition
Widely distributed: deep to skin and hypodermis (subcutaneous fascia) in most body regions
Attached mainly to bone: at origin, insertion, or both
Exceptions: Muscles of facial expression, intrinsic tongue muscles |
|
|
Term
| What are the different skeletal muscle shapes? |
|
Definition
Unipennate
Bicipital
Bipennate
Multipennate
Aponeurotic
Circular
Strap
Digastric |
|
|
Term
| How does skeletal muscle look in longitudinal sections? |
|
Definition
Long, parallel,cells
Perpendicular banding pattern
Fine connective tissue investment around each cell (endomysium) |
|
|
Term
| How does skeletal muscle look in cross section? |
|
Definition
Polygonal cells (paving stones)
End-on view of myofilaments
Peripheral muscle nuclei
Connective tissue surrounds cells (endomysium) |
|
|
Term
| What are the characteristics of skeletal muscle fibers? |
|
Definition
10-100 µm in diameter
2-100 mm long
Multinucleated (peripheral) |
|
|
Term
|
Definition
Organized bundles of myofilaments within each muscle fiber.
Each surrounded by a system of modified smooth ER, termed the sarcoplasmic reticulum.
Abundant mitochondria distributed around and between the myofibrils, providing ready access to ATP required for contraction |
|
|
Term
| Explain the structure of a sarcomere |
|
Definition
Sarcomere: Basic contractile subunit of myofibrils – delineated by Z lines; contains a full A band in the center and ½ I band on each end of A band
A band: Contains thick (myosin) filaments, overlap of thick and thin filaments (potential sites of cross-bridge formation)
I band: Contains thin (actin) filaments, Z line …no thick filaments
Z lines: Bisect each I band, marking end of each sarcomere
H zone: Center of each sarcomere…No thin filaments, thus no thick & thin filament overlap, no cross-bridge formation in this region
M line: Bisects the H zone. Anchors central portion of the thick filaments together |
|
|
Term
| Explain the structure of thin myofilaments |
|
Definition
3 major proteins:
actin, tropomyosin, troponin
G-actin: globular protein - polymerized into double-stranded, helical filamentous actin (F-actin)
Tropomyosin: filamentous protein that blocks the myosin-binding sites on actin
Troponin: complex of 3 globular proteins: TnT, TnI, TnC
TnT: attaches troponin complex to tropomyosin
TnI: inhibits filament interaction -covers myosin binding site on actin
TnC: Ca+2-binding protein for initiation of contraction |
|
|
Term
| Explain the structure of thick myofilaments |
|
Definition
6 polypeptide chains: 2 heavy chains and 4 light chains
Heavy chains:α-helical structure (double helix) –coil around each other as a “tail”
Light chains: form 2 globular heads
Thick Filament: each contains ~200 myosin molecules |
|
|
Term
| What are the secondary sarcomere proteins? |
|
Definition
Thin Filament:
α-actinin & CapZ (ß-actinin): Anchor & weave thin filaments into Z-line
Tropomodulin: caps filament, maintains length
Thick Filament:
Titin: Extends into thick filaments from Z-lines. Flexibly stabilizes thick filament position
MyBP-C: Links thick filaments & titin
M-line:
M-protein
Myomesin: Link thick filaments to M-line |
|
|
Term
| What is the composition of the cell membrane and sarcoplasm of skeletal muscle? |
|
Definition
Sarcolemma: Muscle cell plasma membrane
T-Tubules: Invaginations of sarcolemma into cell interior.
Sarcoplasmic reticulum: Modified endoplasmic reticulum. Surrounds myofibrils.
Terminal cisternae: Expansions of sarcoplasmic reticulum near T-tubules.
Triads: Central T-tubule with 2 adjoining terminal cisternae. Located at A-I band junctions in human skeletal muscle |
|
|
Term
| Explain muscular dystrophy |
|
Definition
X-linked genetic disorder of membrane-associated protein, dystrophin
Dystrophin: Important component in a complex that stabilizes membrane structure, and forms a structural link between muscle fiber and surrounding basal lamina.
Duchenne Muscular Dystrophy (DMD) is the most common form. Involves a frameshift mutation in dystrophin gene |
|
|
Term
| What is the sequence of skeletal muscle fiber development? |
|
Definition
Mesodermal progenitors
myoblasts
early myotube
late myotube |
|
|
Term
| What is the function of myostatin? |
|
Definition
Slows progression of myogenesis. Possibly blocks satellite-cell activation?
Myostatin knockout in mdx mice (model of muscular
dystrophy) shows amelioration of functional deficits & increased muscle mass.
Promise of possible therapeutic use of myostatin inhibitors in treatment of some muscle-wasting diseases (e.g., cancer cachexia) |
|
|
Term
| What is the importance of fiber diameter in skeletal muscle? |
|
Definition
Fiber diameter correlates directly with strength
Small diameter indicates atrophy - disuse, cachexia, neurogenic
large diameter indicates hypertrophy - exercise |
|
|
Term
| How does the sliding filament mechanism work in skeletal muscle? |
|
Definition
A-band: Constant
I-band: Narrows
H-band: Narrows
A-I overlap: Increases
Small changes in individual sarcomere length are multiplied by the number of sarcomeres in a single myofibril.
Bigger cells, more sarcomeres, greater strength |
|
|
Term
| How does the power-stroke work in the sliding filament mechanism |
|
Definition
Myosin head binds to binding site on actin
Conformational change in myosin hinge region drives power stroke
Fresh ATP binds to myosin head allowing release from actin. (ATP hydrolysis “re-cocks” myosin head to “fire” next power stroke |
|
|
Term
| How is skeletal muscle contraction unique? |
|
Definition
Voluntary contraction
Only muscle with neuromuscular junctions
Initiated by direct contact at somatic-motor-neuron axon terminals on specialized sites on the sarcolemma. |
|
|
Term
| What happens at the neuromuscular junction? |
|
Definition
Axon depolarization
Synaptic vesicles fuse with presynaptic membrane
Release of Ach into synaptic cleft
Binding to Ach receptors
Sarcolemmal depolarization
Propagation to T-tubule
Depolarization of Sarcoplasmic Reticulum |
|
|
Term
| How does botulinum toxin affect neuromuscular junctions? |
|
Definition
Toxin complex uptake by receptor-mediated endocytosis
Toxin light chain dissociates and enters cytosol where it cleaves components of the synaptic fusion complex
Prevents fusion of synaptic vesicles with presynaptic membrane and ACh release |
|
|
Term
| Explain myasthenia gravis |
|
Definition
Autoimmune attack mediated by autoantibodies to ACh receptors reduces receptor number and causes inflammatory widening of synaptic cleft and reduction of post-synaptic membrane surface area. Results in progressive loss of neuromuscular control.
Widened cleft increases distance to receptors and likelihood of ACh degradation by acetylcholinesterase (AChE) before reaching already reduced number of receptors |
|
|
Term
| How does calcium cycling in skeletal muscle cells work? |
|
Definition
L-type calcium channels opened by T-tubule depolarization.
Ca++ ions activate ryanodine receptors (RyR) in SR terminal cisterna membranes to release stored Ca++ into cytosol
Cytosolic Ca++ binds TnC on thin filaments; allows contraction.
Ca++ released by TnC after contraction - removed from cytosol by:
1) mitochondria,
2) reuptake by SR Ca++ ATPase (SERCA) in SR membranes,
3) sarcolemmal Na+/Ca++ exchange pumps (NCX). Phospholamban (PLB) inhibits SERCA Activity. |
|
|
Term
| What are the characteristics of a motor unit? |
|
Definition
Each motor unit comprises one axon and all the muscle fibers
Motor units overlap so damage to a single nerve rarely causes complete loss of muscle function
Large Motor Units: 500-1000 muscle fibers, Gross & Postural Movements, e.g., Gastrocnemius
Small Motor Units: 10-20 muscle fibers, Fine movements, e.g., Extraocular Muscles |
|
|
Term
| What is the role of proprioreceptors in skeletal muscle? |
|
Definition
| Proprioceptors monitor muscle tension (stretch). modify contraction strength. |
|
|
Term
| Compare red and white skeletal muscle fibers |
|
Definition
Red fiber:
Type I MyHC,
Slow, Oxidative, Abundant Mitochondria, Slow to Fatigue
Postural Muscles, Endurance
White fiber:
Type II MyHC,
Fast, Glycolytic, Abundant Glycogen, Quickly Fatigued
Most Limb Muscles, Burst Activity |
|
|
