IB Sports, exercise and health science B.1.3.4 Sliding Filament Theory and Molecular Basis of Muscle Contraction Notes

Sliding filament theory explains how actin and myosin produce contraction

1. Huxley first proposed the sliding filament theory in 1954.
2. The Sliding Filament Theory describes how muscle contraction occurs at the molecular level.

Organization of Skeletal Muscle

Skeletal muscle is highly organized and follows a hierarchical structure that allows it to generate force efficiently.

Hierarchy of Skeletal Muscle Organization

1. Muscle (Whole Muscle): Composed of multiple fascicles, surrounded by the epimysium.
2. Fascicle (Bundle of Muscle Fibers): A group of muscle fibers, surrounded by the perimysium.
3. Muscle Fiber (Single Muscle Cell): Contains many myofibrils, surrounded by the endomysium.
4. Myofibril (Contractile Units within a Muscle Fiber): Contains repeating units of sarcomeres, which are the fundamental contractile structures of muscle.
5. Sarcomere (Functional Unit of Contraction): Composed of myofilaments (actin and myosin), responsible for contraction.
6. Myofilaments (Protein Filaments in a Sarcomere): Includes actin (thin filament) and myosin (thick filament), which interact to produce muscle contraction.

Structure and Function of Key Muscle Fiber Components

Skeletal muscle fibers have distinct substructures that work together to enable contraction.

The Structure of a Sarcomere

1. Each sarcomere consists of two main protein filaments, actin and myosin, which are the active structures responsible for muscular contraction.
2. These filaments slide past each other to generate force.

Sarcomere Changes During Contraction

During contraction:

1. The Z-discs move closer together, shortening the sarcomere.
2. The I-band and H-zone decrease in size.
3. The A-band remains unchanged because myosin filaments do not change length.
4. The actin filaments slide over myosin filaments, powered by ATP.

Myofilaments: Actin and Myosin

1. Thin Filament (Actin)

Composition of Actin Filament

1. Actin: A protein that forms a helical structure and provides the foundation for muscle contraction.
2. Troponin: A regulatory protein that binds calcium ions and causes a change in the tropomyosin position.
3. Tropomyosin: A regulatory protein that blocks myosin-binding sites on actin at rest, preventing contraction.

Function of Actin Filament

1. Actin provides the binding sites for myosin heads, which are crucial for the cross-bridge cycle.
2. Troponin and tropomyosin work together to regulate contraction by blocking or exposing the myosin-binding sites on actin.
3. Tropomyosin covers binding sites at rest, preventing contraction.
4. Troponin binds calcium and shifts tropomyosin, exposing binding sites for contraction.

2. Thick Filament (Myosin)

Composition of Myosin Filament

1. Myosin heads: These project from the myosin filaments and have ATPase activity to break down ATP for energy.
2. Myosin tail: A long, fibrous part of the myosin molecule that provides structural support.

Function of Myosin Filament

1. The myosin heads form cross-bridges with actin during contraction, pulling the actin filaments toward the center of the sarcomere, resulting in contraction.

The Sliding Filament Mechanism

1. Activation of the Muscle Fiber

1. The first step in the sliding filament theory is the activation of the muscle fiber through a nerve impulse.
2. This process begins at the neuromuscular junction, which is the synapse where the motor neuron meets the muscle fiber.

Nerve Impulse

1. When the brain sends an electrical signal to the motor neuron, it travels along the neuron to the axon terminal.
2. It triggers the release of the neurotransmitter acetylcholine into the synaptic cleft.

Action Potential

1. The acetylcholine binds to receptors on the sarcolemma (the muscle cell membrane), leading to the generation of an action potential.
2. This electrical signal travels along the sarcolemma and down into the muscle fiber through T-tubules.

Calcium Release

1. The action potential travels through the T-tubules and reaches the sarcoplasmic reticulum (SR), an organelle that stores calcium ions.
2. The action potential causes the SR to release calcium ions into the cytoplasm of the muscle cell.

Excitation-contraction coupling links the nerve signal to contraction

1. Excitation-contraction coupling is the chain of events that links a nerve impulse to a muscle contraction.
2. The action potential travels through the T-tubules deep into the fibre.
3. T-tubules contact the sarcoplasmic reticulum (SR), which releases stored calcium ions into the sarcoplasm.
4. Calcium binds to troponin, tropomyosin shifts off the binding sites, and the cross-bridge cycle begins.

2. Cross-Bridge Formation and Power Stroke

1. Once calcium ions are released, they bind to troponin, a regulatory protein that is attached to the actin filaments.
2. This binding causes a conformational change in the structure of troponin and tropomyosin, another regulatory protein, which shifts away from the myosin-binding sites on the actin filament.

Cross-Bridge Formation

1. With the myosin-binding sites now exposed, the myosin heads attach to the exposed sites on actin, forming cross-bridges.
2. The myosin head is in a cocked position due to previous hydrolysis of ATP.
3. On average, each thick myosin filament is surrounded by six thin actin filaments in skeletal muscle.

Power Stroke

1. The power stroke occurs when the myosin head pivots, pulling the actin filament toward the center of the sarcomere (the M-line).
2. This movement is powered by the energy released from the hydrolysis of ATP.
3. The myosin head moves from a high-energy state to a low-energy state during the power stroke.
4. ADP and inorganic phosphate (Pi) are released as the power stroke occurs.

3. Detachment and Resetting of Myosin Heads

After the power stroke, the myosin head must detach from the actin filament to begin the process again.

Detachment

1. A new molecule of ATP binds to the myosin head, causing it to release from the actin filament.
2. This detachment is necessary for the myosin head to reset and perform another power stroke.

Hydrolysis of ATP

1. Once ATP is bound to the myosin head, it is hydrolyzed into ADP and inorganic phosphate (Pi).
2. This breakdown of ATP provides the energy for the myosin head to reset to a high-energy position, ready to attach to actin again.
3. Without fresh ATP, the myosin head cannot detach from actin and cannot be re-energised for the next stroke.
4. This locked cross-bridge state is the molecular basis of rigor mortis, the stiffening of muscles after death.

Re-cocking of the Myosin Head

The re-cocking of the myosin head places it in a position to attach to the next myosin-binding site on the actin filament.

4. Muscle Relaxation

Calcium Ion Reuptake

1. When the nerve impulse stops, calcium ions are actively pumped back into the sarcoplasmic reticulum by calcium pumps.
2. This reduces calcium ion concentration in the sarcoplasm, leading to muscle relaxation.

Blocking of Myosin-Binding Sites

1. As calcium ions are removed, troponin and tropomyosin return to their resting conformation, covering the myosin-binding sites on actin.
2. This prevents further cross-bridge formation, leading to the relaxation of the muscle.

Control of Muscle Force

Rate Coding (Frequency of Activation) and Force Generation

1. The rate at which a motor neuron fires electrical impulses determines how much force is generated by the muscle.
   1. Low Frequency: When motor units are activated at a low frequency, individual twitches are separated, and the muscle produces a low force output.
   2. High Frequency: As the frequency increases, twitch summation occurs, where successive muscle contractions overlap, leading to stronger contractions. At very high frequencies, tetanic contraction occurs, a sustained contraction without relaxation.

Technology reveals what the eye cannot see

1. The sliding filament theory was only possible because Huxley had access to an electron microscope in 1954.
2. X-ray diffraction reveals the structure of actin and myosin at atomic resolution.
3. Fluorescent calcium dyes let researchers watch calcium ions flood out of the SR in real time.
4. High-speed atomic force microscopy can image individual myosin heads mid-power stroke.