Lecture 7: Skeletal Muscle Flashcards
Characteristics of skeletal muscle cells
AKA striated muscle fiber. Very large, elongated, and multinucleated. Fuse from undifferentiated myoblasts.
Satellite cells
Quiescent skeletal muscle stem cells. Proliferate in response to strain/injury and mediate hypertrophy of other fibers in repair.
Skeletal muscle striations
Composed of cytosolic thick myosin and thin actin filaments.
Myofibril
Thick/thin filament bundles that attach to tendons and extend end to end within muscle cells, filling most of the cytoplasm
Thick filaments
Primarily made of myosin. Tails extend along axis of thick filament with heads extending out the sides as cross bridges
Thin filaments
Primarily made of actin in 2 helical intertwined chains; also nebulin, troponin, and tropomyosin. Each actin molecule is a myosin binding site
Myosin structure
Composed of 2 heavy chains and 4 light chains. Heavy chains intertwine into a long tail and form the two globular heads of the motor region. Light chains are at the neck.
Myosin motor head region
Responsible for contacting the thin filament and exerting force. Contains one binding site for actin (thin-f) and another for ATP (myosin-ATPase)
Sarcomere
Basic contractile unit. Bounded by Z-lines and composed of overlapping thick + thin filaments and titin
Sections of sarcomere
Z-line, M-line, I band, A band, H zone
Z-line (disc)
Defines boundary of sarcomere and anchors thin filaments + titin
M-line (disc)
Line (disc) in middle of sarcomere that binds thick filaments + titin
I band
Area of sarcomere that contains only thin filaments, no thick
H zone
Area of sarcomere that contains only thick filaments, no thin
A band
Anisotropic band. Area of sarcomere with entire thick filament. Contains overlapping thick + thin filaments
Titin
Protein that gives sarcomere its elastic properties. Links to M-lines and thin filaments.
Transverse arrangement of thick and thin filaments
Each thick filament is surrounded by a hexagon of thin filaments; each thin-f is surrounded by a triangle of thick-f. Thus there are about 2x as many thin as there are thick filaments.
Sarcoplasmic reticulum
Network of tubules/sacs that form sleeves around each myofibril and are responsible for storing/releasing Ca2+
Terminal cisternae
Located at ends of sarcoplasmic reticulum. Store a high concentration of Ca2+ through calsequestrin and are connected by tubes.
Transverse tubules
Invaginations continuous with the sarcolemma and whose lumen is continuous with the ECF. Allow APs to penetrate into the muscle fiber.
Contraction vs relaxation
Activation of force generating cross-bridges in muscle. Relaxation is inactivation
Alpha motor neuron properties
Alpha motor neurons innervate skeletal muscle fibers and are myelinated + large diameter. 1 motor neuron axon branch innervates 1 fiber, so 1 motor neuron innervates many fibers.
Motor unit
Comprised of a motor neuron and all its innervated fibers. All fibers within a motor unit get stimulated together.
Motor end plate
Sarcolemma under the motor axon terminal with junctional folds for more surface area. Contains ACh receptors.
Neuromuscular junction
Structure composed of the motor axon terminal and the motor end plate
Motor neuron action potentials per muscle fiber action potentials
The NMJ has 1:1 transmission (1 neuron AP means 1 muscle fiber AP)
Acetylcholinesterase
Enzyme that breaks down ACh at the NMJ for reuptake and recycling.
How does curare affect muscle contraction?
Inverse agonist for nicotinic ACh receptors. Binds with high affinity without opening channels while resisting AChesterase breakdown, preventing fiber activation.
Tropomyosin
Protein chains 7 g-actin long that run along the thin-f and partially cover actin’s myosin-binding site, preventing cross-bridge contact at rest
Troponin
“Staples” tropomyosin to its blocking position on actin, 1 per tropomyosin. Complex of TnI, TnT, TnC.
TnI
Inhibitory subunit of troponin. Binds complex + tropomyosin to actin filament
TnT
Tropomyosin-binding subunit of troponin
TnC
Calcium-binding subunit of troponin
Excitation-contraction coupling
Sequence by which an AP in the sarcolemma activates force-generating mechanism
How do organophosphates affect skeletal muscle?
Organophosphates inhibit AChesterase, preventing repolarization for further APs. Can be rescued with pralidoxime
What are rocuronium and vecuronium used for and why?
Both are used in anesthesia. They are nondepolarizing long-lasting NMJ blocks that act similar to curare
How does botulinum toxin affect the NMJ?
Botunlinum cleaves SNARE proteins, preventing vesicle fusion and thus NT release.
Dihydropyridine receptor (DHPR)
The DHPR is a transmembrane voltage-sensitive Ca2+ channel in the t-tubule that acts as a voltage sensor for the muscle fiber
Ryanodine receptor (RyR)
Sarcoplasmic reticulum transmembrane calcium channel which is connected to the DHPR by a foot process, allowing the DHPR to open the RyR and briefly release calcium from the SR on stimulation.
How much calcium is released from 1 skeletal muscle AP relative to the muscle fiber?
1 AP typically releases enough calcium to briefly saturate all troponin binding sites
Sliding filament mechanism
Contraction happens by sliding thick and thin filaments past each other, shortening sarcomeres without changing filament length
Cross-bridge cycle (Lymn Taylor Model)
- Actin binding (tropomyosin moves)
- Power stroke (ADP leaves)
- Dissociation from actin (ATP binding)
- Myosin cocking (ATP hydrolysis)
Roles of ATP in skeletal muscle contraction
- Maintain membrane excitability through resting potential
- Regulate cytosolic Ca++
- Provide energy for cross-bridge motion
- Dissociate myosin from actin
Rigor mortis
Without fresh ATP calcium leaks out of the SR -> cross-bridges power stroke but can’t release actin -> muscle rigidity
Rate limiting step of myosin ATPase
Myosin ATPase is rate limited by product dissociation (releasing ADP + Pi); bound actin increases this step by over 2000X
SERCA
Sarcoendoplasmic Reticulum Calcium ATPase: removes cytosol Ca++ and pumps back into SR; works much slower vs action potential time, so 1 AP lasts 1-2 ms but the corresponding contraction lasts ~100 ms.
