CA

2-6 Muscle Filaments

Thick Filaments

  • Myosin Overview

    • Myosin aggregates form thick filaments, characterized by:

      • Long fibrous “tail” connected to globular “head”

      • Head has:

        • Actin-binding site

        • ATP-binding site

        • Pivot hinge

        • ATPase activity

    • Myosin cross-bridge head functions as the “working” part.

Myosin ATPase Function

  • The globular head of myosin performs ATP binding and hydrolysis:

    • ATP splits into ADP + Pi, activating the globular head

    • Activation causes the head to pivot, preparing it to pull actin.

Actin Filaments

  • Structure of Actin

    • Composed of 300-400 G-actin subunits in a double row twisted to form a helical backbone.

    • Thin Filaments Composition:

      • Contains two regulatory proteins:

        • Troponin complex

        • Tropomyosin

Resting State of Actin

  • In the resting state, myosin binding sites on actin are blocked by tropomyosin.

  • The troponin complex holds tropomyosin in place, preventing myosin binding (crossbridge formation).

  • At rest, regulatory proteins on the thin filament inhibit interaction between actin and myosin.

Activation of Contraction

  • When calcium ions (Ca2+) bind to troponin, it causes:

    • Tropomyosin to shift away from the myosin-binding site on actin.

    • Ca2+ released into the cytosol allows myosin to bind to actin.

Excitation-Contraction Coupling in Skeletal Muscle

  • Components:

    • Neuromuscular Junction:

      • Axon terminal releases Acetylcholine (ACh), binding to nicotinic receptors on the sarcolemma.

      • Ligand-gated channels open, leading to Na+ influx and depolarization.

    • Action potentials propagate along transverse tubules, opening voltage-gated Ca2+ channels in the sarcoplasmic reticulum (SR).

    • Ca2+ diffuses out into the sarcoplasm, binds to troponin, initiating contraction.

Power Stroke and Contraction Cycle

  • Hydrolysis of bound ATP energizes the myosin head, enabling it to bind to actin.

  • The release of Pi initiates the power stroke, pulling thin filament toward the center.

  • After the power stroke, ADP is released, and a new ATP molecule binds to myosin, causing it to release actin.

  • This cycle continues, causing sarcomere shortening and force production.

Role of Calcium in Contraction

  • Contraction is dependent on calcium activating the thin filament:

    • Myosin must be energized and there must be no blocking from tropomyosin.

Relaxation State

  • In a relaxed state:

    • Myosin head is cocked and weakly attached to actin.

    • Tropomyosin partially obstructs the binding site on actin.

Summary of Calcium Influence

  • Increased cytosolic Ca2+ levels activate contraction by:

    • Binding to troponin and shifting tropomyosin away from actin's myosin-binding site.

Cross-Bridge Cycling

  • Myosin attaches to actin, causing a power stroke that moves actin towards the M-line.

  • As long as Ca2+ is present, cross-bridges continue to cycle, resulting in muscle contraction.

Mechanism of Sarcomere Shortening

  • Contraction involves:

    • Cross-bridges binding to actin leading to sarcomere shortening and force generation.

    • Despite illustration suggesting simultaneous activity, many cross-bridges cycle asynchronously within the muscle fiber.