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.