Overview
This lecture covers the development of muscle biology from 1864 to 1969, focusing on the origins of muscle research and the eventual acceptance of the sliding filament theory of muscle contraction.
Muscle Architecture and Function
- Skeletal muscles generate movement through coordinated contraction using ATP as their energy source.
- Muscles are composed of bundles called fascicles, which contain muscle fibers (cells).
- Muscle fibers are syncytia (formed from fused myoblasts), long and thin, and filled with myofibrils.
- Cardiac muscle consists of shorter, individual cells, but both cardiac and skeletal muscles are striated due to repeating sarcomeres.
- Sarcomeres contain overlapping thin (actin) and thick (myosin) filaments, responsible for contraction.
Early Muscle Research (1864-1940s)
- Myosin (main protein in muscle) was first isolated in 1864.
- Striations in muscle were classified into dark A bands (anisotropic) and light I bands (isotropic).
- Early observations showed A bands remain constant in length during contraction, while I bands shorten.
- Prevailing dogma believed contraction was due to folding or coiling of filaments, not sliding.
Key Discoveries (1939-1950s)
- In 1939, myosin was identified as both a structural protein and an ATPase enzyme.
- Actin was identified as an activator of myosin; together, actin and myosin could reproduce contraction in vitro.
- Despite new evidence, the field was slow to abandon the folding model due to entrenched beliefs.
Sliding Filament Theory (1954 and onward)
- In 1954, A.F. Huxley and H.E. (Hugh) Huxley independently provided evidence for the sliding filament theory.
- Both demonstrated that during contraction, the A band (myosin) length stays the same, but the I band (actin) shortens.
- Extraction experiments confirmed myosin is located in the A band and actin in the I band.
- Initial electron microscopy lacked resolution, but advancements soon confirmed the presence of cross-bridges (myosin heads) between filaments.
Functional and Structural Insights
- Greater overlap of actin and myosin filaments results in increased force generation.
- Electron microscopy revealed a hexagonal array of thick and thin filaments and the structure of cross-bridges.
- X-ray diffraction studies showed mass shifts during contraction, supporting the sliding model.
Swinging Cross-Bridge Model (1969)
- H.E. Huxley proposed that myosin heads bind actin, swing (rotate) to move actin, release, then repeat, producing contraction.
Key Terms & Definitions
- Sarcomere — the basic contractile unit of muscle, defined by repeating patterns of actin and myosin filaments.
- Actin — thin filament protein in muscle that interacts with myosin for contraction.
- Myosin — thick filament protein with ATPase activity, responsible for force generation in muscle.
- A band — dark band in striated muscle, contains thick myosin filaments.
- I band — light band in striated muscle, contains thin actin filaments.
- Sliding Filament Theory — theory stating muscle contracts by sliding of actin past myosin, shortening the sarcomere.
- Cross-bridge — myosin head that binds to actin to facilitate contraction.
Action Items / Next Steps
- Review diffraction theory and muscle x-ray patterns as referenced in the lecture.
- Prepare for Part Two of the lecture series on muscle biology.