Skeletal Muscle Structure Quiz

Skeletal Muscle Structure

• Myosin: Composed of two heavy chains, a head region containing ATPase activity and an actin-binding site, two light chains (regulatory and essential), a neck region allowing the head to pivot, and a tail region that forms a coiled-coil structure.
• Actin: Part of the thin filament and interacts with myosin. Key proteins associated with actin include:
  • Troponin: Ca++ sensitive protein, uncovers myosin binding site with increased Ca++ levels.
    • TnC: Ca++ sensing
    • TnI: inhibits actin/myosin interaction
    • TnT: tethers troponin to tropomyosin
• Thick filaments: Formed by two bundles of myosin, joined tail-to-tail.
• Sarcomere: The functional unit of skeletal muscle, defined between two Z disks.
  • Z disk: Anchors thin filaments.
  • Overlap: Between thick and thin filaments results in banding patterns.
  • Crossbridge: Region of overlap between thick and thin filaments.

Sarcomere Proteins

• α-Actinin: Binds thin filaments to the Z discs.
• Titin: A large protein that attaches to the Z disk at one end and the thick filament at the other. It acts as a spring limiting sarcomere stretch and centers the thick filaments.
• Dystrophin: A large protein associated with Z disks that anchors the contractile array to the cytoskeleton and surface membrane, aligning Z disks in adjacent myofibrils and muscle fibers.

Clinical Connection: Muscular Dystrophy

• Duchenne muscular dystrophy: Caused by a recessive X-linked mutation in the dystrophin gene.
• Loss of dystrophin function: Prevents cytoskeleton and contractile machinery from attaching to the sarcolemma, resulting in muscle necrosis and wasting.

Cross-Bridge Cycling and Contraction

• Cross-bridge cycling: A series of events involving myosin heads attaching to actin filaments, pulling the thin filaments, releasing from actin, and returning to their original position.
• Calcium regulations: Calcium binds to troponin, causing a conformational change and exposing the myosin binding sites on actin, facilitating cross-bridge cycling and muscle contraction.
• Sliding filaments: The thin filaments slide past the thick filaments, shortening the sarcomere.

Skeletal Muscle Mechanics

• Preload: Stretching a muscle to optimize actin and myosin interaction.
• Optimal sarcomere length: The resting skeletal muscle length maximizes the potential for crossbridge formation.
• Overstretching: Can separate thick and thin filaments, preventing contraction.
• Peak muscle performance: Occurs when crossbridge formation is maximized.

Organizational Hierarchy of Skeletal Muscle

• Skeletal muscle: Composed of muscle fibers.
• Muscle fibers: Composed of myofibrils.
• Myofibrils: Composed of sarcomeres.

Sarcoplasm

• Sarcoplasm: The cytoplasm of the muscle cells.
• Components: Rich in Mg2+, phosphates, glycogen granules, myoglobin, and mitochondria.

Membrane Systems of the Sarcomere

• T-Tubules: Carry action potentials from the cell surface to structures involved in Ca++ release.
• Sarcoplasmic reticulum: Specialized organelle responsible for Ca++ storage and release.
  • SERCA pumps: Maintain the Ca++ gradient within the SR.
  • Calsequestrin: Binds Ca++ and helps prevent Ca++ leakage from the SR.
• Triads: Junctions between T-tubules and the SR, critical for excitation-contraction coupling.

Neuromuscular Junction (NMJ)

• Synapse: Junction between motor neurons and skeletal muscle fibers.
• Neurotransmitter: Acetylcholine (ACh) released from the presynaptic terminal.
• Postsynaptic membrane: Contains ACh receptors.

Skeletal Muscle Action Potential

• Depolarization: Caused by the influx of Na+ ions.
• Repolarization: Caused by the efflux of K+ ions.
• Refractory period: A period of time after an action potential when another action potential cannot be generated.

Ion Chemical Gradients

• Potassium (K+): Is higher inside the cell than outside.
• Sodium (Na+), Chloride (Cl-), Calcium (Ca++): Are higher outside the cell than inside.

Membrane Potential Changes

• Resting membrane potential: Approximately -70 mV (negative inside).
• Depolarization: Caused by Na+ influx, membrane potential becomes less negative.
• Repolarization: Caused by K+ efflux, membrane potential returns to resting.

Action Potential Characteristics

• All-or-none principle: Action potentials occur in their full strength or not at all.
• Conduction: Action potentials propagate along the membrane without decreasing in amplitude.

Tissue-Specific Action Potentials

• Skeletal muscle: Action potentials have a fast rise to peak and a relatively long duration.

Clinical Connection: Myasthenia Gravis

• Autoimmune condition: Antibodies against ACh receptors.
• Effect on NMJ: Interferes with normal signaling at the NMJ.
• Symptoms: Muscle weakness.
• Treatment: Anticholinesterase inhibitors.

Excitation-Contraction Coupling

• Electrical to mechanical transduction: Action potentials trigger muscle contraction.
• T-tubule function: Carry action potentials to triads.
• Triad function: Trigger Ca++ release from the SR.

Calcium Delivery to Muscle Fibers

• Depolarization of T-tubules: Leads to Ca++ release from the SR.

Excitation-Contraction Coupling Mechanics

1. Action potential: Propagates down the T-tubules
2. T-tubule depolarization: Triggers Ca++ release from the SR.
3. Ca++ binds to troponin: Exposing myosin binding sites on actin.
4. Cross-bridge cycling: Causes muscle contraction.
5. Ca++ removal: Muscle relaxation.