Skeletal Muscle Contraction Study Pack

Organizational Levels from Muscle to Myofilament

• •Each skeletal muscle fiber is a single multinucleated cell enclosed by a plasma membrane called the sarcolemma and a specialized endoplasmic reticulum called the sarcoplasmic reticulum.
• •The cytoplasm of a muscle fiber, called the sarcoplasm, is packed with thread-like myofibrils that run the length of the cell and contain the contractile machinery.
• •Myofibrils are divided into repeating contractile units called sarcomeres, bounded at each end by Z-discs; a single myofibril may contain thousands of sarcomeres in series.

The Sarcomere's Protein Filaments

• •Thick filaments are composed of myosin II, a motor protein whose globular heads project outward and can bind actin and hydrolyze ATP.
• •Thin filaments are built from F-actin (polymerized actin), with two regulatory proteins wound around them: tropomyosin, a rope-like protein that physically blocks myosin-binding sites at rest, and the troponin complex (troponin T, I, and C), which anchors tropomyosin and responds to calcium.
• •The titin protein runs from the Z-disc to the M-line, acting as a molecular spring that keeps thick filaments centered and resists over-stretching.

Landmark Zones Visible in a Sarcomere

• •The A-band spans the full length of the thick filaments and remains constant in width during contraction.
• •The I-band, which contains only thin filaments, narrows during contraction as thin filaments slide inward.
• •The H-zone, the region of thick filaments not overlapped by thin filaments, disappears entirely at full contraction.

Acetylcholine Release from the Motor Neuron Terminal

• •When an action potential reaches the axon terminal of a motor neuron, voltage-gated Ca²⁺ channels open, and the influx of calcium triggers synaptic vesicles to fuse with the presynaptic membrane and release acetylcholine (ACh) into the synaptic cleft.
• •ACh diffuses across the cleft and binds to nicotinic acetylcholine receptors on the motor end plate, a specialized region of the sarcolemma directly opposite the nerve terminal.

Generation of the Muscle Action Potential

• •Nicotinic receptors are ligand-gated ion channels; ACh binding opens them, allowing simultaneous Na⁺ influx and K⁺ efflux, with net depolarization of the motor end plate producing an end-plate potential.
• •If the end-plate potential is large enough, it triggers a self-propagating action potential along the sarcolemma in both directions from the end plate.

Signal Termination and the Role of Acetylcholinesterase

• •Acetylcholinesterase, anchored in the synaptic cleft, rapidly hydrolyzes ACh into acetate and choline, ending receptor activation and ensuring that a single motor neuron firing produces a single muscle action potential rather than sustained depolarization.
• •Choline is recycled back into the motor neuron terminal for ACh resynthesis.

T-Tubule Propagation of the Action Potential

• •The sarcolemma forms deep tubular invaginations called transverse tubules (T-tubules) that penetrate to the center of the fiber, ensuring that the action potential reaches the interior of the cell almost simultaneously with its arrival at the surface.
• •Each T-tubule lies in close contact with two terminal cisternae of the sarcoplasmic reticulum, forming a structure called a triad.

Calcium Release from the Sarcoplasmic Reticulum

• •Voltage-sensitive proteins in the T-tubule membrane, called dihydropyridine receptors (DHPRs), act as voltage sensors; when depolarized, they mechanically activate ryanodine receptors (RyRs) on the adjacent sarcoplasmic reticulum membrane.
• •Activated RyRs open as calcium channels, releasing a surge of Ca²⁺ from the sarcoplasmic reticulum lumen into the sarcoplasm, raising intracellular Ca²⁺ concentration from roughly 10⁻⁷ M at rest to approximately 10⁻⁵ M.

Troponin-Tropomyosin Activation by Calcium

• •Ca²⁺ binds to troponin C, inducing a conformational change in the troponin complex that physically displaces tropomyosin away from the myosin-binding sites on actin.
• •Once the binding sites are exposed, myosin heads can attach to actin and initiate the cross-bridge cycle.

• •Step 1 — Energized Myosin Head (Cocked State)
• •ATP binds to the myosin head and is hydrolyzed to ADP and inorganic phosphate (Pᵢ); the energy released causes the head to pivot into a high-energy, cocked position perpendicular to the thick filament.
• •ADP and Pᵢ remain bound to the myosin head while it is in this cocked configuration.
• •Step 2 — Cross-Bridge Formation
• •The cocked myosin head binds to an exposed active site on the actin filament, forming a cross-bridge.
• •Step 3 — Power Stroke and Filament Sliding
• •Release of Pᵢ triggers the power stroke: the myosin head rotates approximately 45°, pulling the thin filament toward the M-line by about 10 nm.
• •ADP is released at the end of the power stroke, leaving the myosin head tightly bound to actin in what is called the rigor state.
• •Step 4 — Detachment and Reset
• •A new ATP molecule binds to the myosin head, causing it to release actin; the head then hydrolyzes that ATP to re-enter the cocked state, ready for another cycle.
• •If ATP is absent (as occurs after death), myosin remains locked to actin, producing rigor mortis.

Net Effect on Sarcomere Geometry

• •Because hundreds of myosin heads cycle asynchronously along each thick filament, the thin filaments are pulled continuously toward the center, shortening the I-band and H-zone while the A-band length is unchanged — the core prediction of the sliding filament model.