The sliding filament theory is a fundamental concept in muscle physiology that explains how muscles contract and produce force. The theory is based on the interaction of two types of protein filaments within muscle fibers: actin (thin filaments) and myosin (thick filaments). Understanding this theory provides insight into how muscles work at a molecular level to produce movement and force.
Skeletal Muscle Structure
Skeletal muscle fibers, also known as myofibers, are long, cylindrical, multinucleated cells that form during development by fusion of precursor muscle cells. These fibers are specialized for contraction and contain several important structures.
- Sarcoplasmic reticulum (SR): A specialized type of smooth endoplasmic reticulum that stores and releases calcium ions (Ca²⁺), which are essential for muscle contraction.
- Myofibril: These are the contractile elements of the muscle fiber and consist of thick myosin filaments and thin actin filaments arranged in a repeating pattern along the length of the muscle fiber.
- T-tubule (transverse tubule): An extension of the sarcolemma (sarcolemma) that permeates the muscle fiber allows the action potential to reach the SR.
- Mitochondria: They are found in large numbers within muscle fibers and provide the ATP needed for contraction.
Structure of the sarcomere
Sarcomere is characterized by a highly organized structure that can be seen under a light microscope as a repeating unit with alternating dark and light bands. The main structural elements of a sarcomere are:
- Z-Disc (Z-Line): Z-discs define the boundaries of each sarcomere and anchor actin thin filaments. They are located at both ends of the sarcomere and play a key role in maintaining the structural integrity of the sarcomere. Z-discs also serve as attachment sites for titin, a large protein that contributes to the elasticity of the sarcomere.
- band: The A-band is the region of the sarcomere that contains the entire length of the thick filament (myosin). It appears dark under a microscope because myosin and actin filaments overlap. The A-band does not change length during muscle contraction; it represents the length of the myosin filament, which does not shorten and passes over the actin filament.
- I-Band: I-bands are bright regions of the sarcomere that contain only thin filaments (actin) and extend from the end of one A-band to the beginning of the next A-band. The I-band shortens during muscle contraction as the actin filaments slide inward and overlap more with the myosin filaments.
- H Zone: The H-zone is a central region within the A-band that contains only thick filaments and no overlapping thin filaments. It appears brighter than the rest of the A-band. During contraction, the H-zone narrows as actin filaments slide into this region, decreasing the distance between adjacent myosin filaments.
- M-Line: The M-line is a structural protein assembly located in the center of the sarcomere, within the A-band. It anchors the thick filaments and helps maintain their alignment during contraction. The M-line is composed of myomesin and other proteins that stabilize myosin filaments.
Myosin: Structure, synthesis, classification, and function – The Science Notes
Actin: Structure, Function, and Dynamics – Science Notes
Sliding Filament Theory
The sliding filament theory, originally proposed by AF Huxley and R. Niedergerke, and later expanded by HE Huxley and J. Hanson, explains how muscle contraction occurs. According to this theory:
- Sarcomere structure during contraction: When a muscle contracts, the A band, which contains the myosin filaments, stays the same length, but the I band, which contains the actin filaments, shortens. This shortening occurs because the actin filaments thread through the myosin filaments.
- Actin-myosin interaction: Myosin heads bind to actin filaments and form cross-bridges that initiate a power stroke via ATP hydrolysis, pulling the actin filament towards the center of the sarcomere, initiating contraction.
Steps of the sliding filament theory
According to the sliding filament theory, muscle contraction occurs when actin and myosin filaments slide past each other, shortening the sarcomere without changing the length of the filaments themselves. This process involves several key steps:
1. Action potential and calcium release:
- Action potentials from motor neurons reach the neuromuscular junction and cause the release of acetylcholine (ACh).
- ACh binds to receptors on the sarcoplasmic membrane, causing depolarization and the initiation of an action potential that propagates along the T-tubule.
- The action potential stimulates the SR, releasing Ca²⁺ into the sarcoplasm.
2. Calcium binding to troponin:
- Calcium ions bind to troponin C, a component of the troponin complex associated with thin filaments.
- This binding induces a conformational change in the troponin-tropomyosin complex, dissociating tropomyosin from its actin-binding site.
3. Cross-bridge formation:
Once the binding sites are exposed, high-energy myosin heads attach to actin and form cross-bridges.
ATP bound to myosin is hydrolyzed to ADP and inorganic phosphate, providing energy for the power stroke.
4. Power stroke and filament slide:
- During the power stroke, the myosin head rotates and pulls the actin filaments towards the M-line, shortening the sarcomere.
- After ADP and phosphate are released from the myosin head, a new ATP molecule binds and the myosin head separates from the actin.
5. Reactivation of myosin heads:
- ATP is hydrolyzed to ADP and phosphate, reenergizing the myosin head and preparing it for the next binding and pulling cycle.
- This cycle repeats as long as calcium ions are present in the sarcoplasm.
6. Muscle relaxation:
- When the action potential stops, calcium ions actively return to the SR.
- When calcium concentrations decrease, tropomyosin again covers the actin-binding sites, preventing the formation of further cross-bridges and causing muscle relaxation.
Regulation of muscle contraction
Muscle contraction is tightly controlled by several factors, including calcium ions and ATP.
- The role of calcium: Calcium ions play a key role in muscle contraction by binding to troponin, a regulatory protein associated with actin filaments. In the absence of calcium, tropomyosin covers the myosin-binding sites on actin, preventing the formation of cross-bridges. Elevated calcium levels cause a conformational change in troponin that displaces tropomyosin from its binding sites, allowing the myosin heads to attach to actin.
- ATP’s role: ATP is essential for muscle contraction, providing the energy needed for muscle contraction, separating myosin from actin, and hydrolysis of ATP, which returns the myosin head to the cocked position. Without enough ATP, muscles cannot relax and remain contracted, leading to conditions such as rigor mortis.
Detailed mechanisms and observations
- Molecular mechanism: The detailed molecular mechanism of the filament sliding theory has been elucidated through various studies. For example, high-resolution microscopy and X-ray diffraction studies have provided insight into the structural changes that occur during muscle contraction. These studies have confirmed that sliding of actin filaments past myosin is responsible for sarcomere shortening.
- Protein Structure: The structural details of myosin and actin filaments have been further explored by techniques such as cryo-electron tomography and atomic force microscopy, which have revealed the precise arrangement of actin and myosin, and the structural changes that occur during the cross-bridge cycle.
Evidence supporting the theory
Some observations that support the sliding filament theory:
- Sarcomere shortening: During muscle contraction, the distance between the Z disks decreases, the H zone narrows, and the I band shortens, while the A band remains unchanged.
- Microscopic studies: Electron microscopy revealed that actin and myosin filaments did not change length but instead slid past each other.
Conclusion
The sliding filament theory represented a major advance in our understanding of muscle contraction, revealing the complex molecular interactions that shorten muscle fibers and generate force. By elucidating the roles of actin, myosin, ATP, and calcium, scientists have gained valuable insights into muscle function and regulation. Despite its comprehensive nature, ongoing research continues to refine our understanding and address unanswered questions. Continued research in muscle physiology promises to advance our knowledge of this fundamental physiological process and discover new insights and applications.
References and Further Reading
- Huxley, AF, & Niedergerke, R. (1954). Structural changes in muscle during contraction: interference microscopy of living muscle fibres. Nature, 173971-973.
- Huxley, H. E., & Hanson, J. (1954). Changes in muscle striations during contraction and extension and their structural interpretation. Nature, 173973-976.
- Spudich, JA (2001). The myosin swing cross-bridge model. Nature Reviews Molecular and Cellular Biology, 2387-392.
- Lehman, W., Craig, R., & Vibert, P. (1994). Ca2+-induced tropomyosin movement in limulus thin filaments revealed by three-dimensional reconstruction. Nature, 36865-67.
- Goody, RS (2003). The missing link in the muscle crossbridge cycle. Nature Structural Biology, 10773-775.
