Illustrate actin myosin sliding mechanism of muscle contraction and relaxation. (IFS 2023, 15 Marks)

Introduction

The actin-myosin sliding mechanism is a fundamental process that underlies muscle contraction and relaxation. This mechanism involves the interaction between two key proteins, actin and myosin, which are responsible for generating the force required for muscle movement. 

Structure of Muscle Fiber

• Muscle Fiber: Composed of many myofibrils, which in turn are made up of sarcomeres—the basic functional units of muscle contraction.
• Sarcomere: The repeating structural unit of the myofibril, consisting of:
  
  • Actin Filaments (Thin Filaments): Composed of actin, troponin, and tropomyosin.
  • Myosin Filaments (Thick Filaments): Composed of myosin molecules that have heads capable of binding to actin.

Mechanism of Muscle Contraction (Sliding Filament Model)

• Resting State:
  
  • In the relaxed muscle, the actin and myosin filaments are not interacting.
  • The myosin heads are in a "cocked" position, ready to bind with actin, but are blocked by the tropomyosin on actin filaments.
  • The muscle is in a low-energy state, and calcium ions are stored in the sarcoplasmic reticulum (SR).
• Activation:
  
  • When a muscle is stimulated by a nerve impulse, calcium ions are released from the sarcoplasmic reticulum into the cytoplasm of the muscle fiber.
  • Calcium binds to troponin, a protein complex on the actin filament, causing a conformational change that shifts tropomyosin away from the myosin-binding sites on actin.
• Cross-Bridge Formation:
  
  • With the binding sites exposed, the myosin heads attach to the actin filaments, forming what is known as a cross-bridge.
  • This binding occurs at the active site of actin where the myosin heads can attach.
• Power Stroke:
  
  • Once the myosin heads bind to actin, they undergo a conformational change, pulling the actin filament toward the center of the sarcomere. This movement is called the power stroke.
  • The myosin head pivots, dragging the actin filaments, and in the process, ADP and inorganic phosphate (Pi) are released from the myosin head.
• ATP Binding and Cross-Bridge Detachment:
  
  • After the power stroke, a new ATP molecule binds to the myosin head.
  • The binding of ATP causes the myosin head to detach from the actin filament.
• ATP Hydrolysis and "Re-cocking" of Myosin Head: The ATP is hydrolyzed to ADP and Pi, which re-energizes the myosin head and returns it to its cocked position, ready for another cycle of interaction with actin.
• Repetition of the Cycle: This cycle of cross-bridge formation, power stroke, and detachment repeats as long as calcium ions remain present and ATP is available, resulting in the continuous sliding of actin filaments past myosin filaments and thus muscle contraction.

Mechanism of Muscle Relaxation

• Cessation of Nerve Impulse: When the nerve impulse stops, calcium ions are actively pumped back into the sarcoplasmic reticulum by the calcium ATPase pumps.
• Troponin-Tropomyosin Complex: As calcium ions are removed, troponin and tropomyosin return to their resting conformation, covering the myosin-binding sites on the actin filament.
• Termination of Cross-Bridge Formation: Without the calcium-troponin interaction, myosin heads can no longer bind to actin, and the cross-bridge cycle ceases.
• Relaxation: As a result, the sarcomere lengthens back to its relaxed state, and the muscle as a whole relaxes.

Conclusion

The actin-myosin sliding mechanism is a complex process that underlies muscle contraction and relaxation. This mechanism involves the interaction between actin and myosin filaments, which generate the force required for muscle movement.