Molecular basis of Skeletal Muscle Contraction

The ppt aims to explain the molecular basis of skeletal muscle contraction and certain applied aspects of the same. Sources include Guyton and Hall's Textbook of Physiology (South-Asia edition, Vol. 2) and C.L. Ghai's Textbook for Practical Physiology.

1. MOLECULAR BASIS OF SKELETAL MUSCLE CONTRACTION

2. STRUCTURE OF A SKELETAL MUSCLE

3. Muscle Proteins Contractile muscle proteins- Actin Myosin Structural muscle proteins- Titin Desmin Actinin Dystrophin-Glycoprotein complex Regulatory proteins- Troponin I, T, C Relaxation proteins- Lead to Calcium ion efflux from the sarcoplasm and subsequently relaxation. 20% of muscle mass is protein.

4. Structure of a Skeletal Muscle Smallest structure (observed under a light microscope) present is a muscle fibre . It has a plasma membrane (a.k.a. Sarcolemma) and an outer fibrous covering k/a endomysium .) 10 to 100 or more muscle fibres together form a muscle fasciculi . These muscle fasciculi are wrapped around in a sheath of connective tissue k/a perimysium . 50 to 100 or more muscle fasciculi together form a muscle . The muscle is wrapped around in a sheath of connective tissue k/a epimysium .

5. Muscle Fibre Each muscle fibre is composed of a few hundred to a few thousand myofibrils . Each myofibril contains 1500 myosin filaments and 3000 actin filaments. Each myofibril contains repeating units k/a sarcomere . Sarcomeres form the basic units of contraction.

6. Actin Filament(s) Responsible for formation of the light band of a sarcomere, a.k.a. I bands ( dark bands / A band is formed by Myosin filaments ) due to their isotropic response to polarised light. Are formed by G-Actin and tropomyosin molecules. G-Actin molecules polymerise to form an F-Actin protein molecule. The double stranded F-Actin protein molecule is wound in a helix, such that each G-Actin molecule has an active site ( ADP molecules )

7. Tropomyosin molecules are attached spirally around the helical F-Actin molecule. Attached to the tropomyosin molecules is a loosely bound complex of 3 troponin proteins- Troponin I (Actin binding) Troponin T (Tropomyosin binding) Troponin C (Calcium ion binding) This performs the function of binding the tropomyosin molecule to the F-Actin molecule . Hypothesized that the tropomyosin-troponin complex is responsible for physically masking the active site of the actin filament.

8. Myosin Filament(s) Composed of multiple myosin molecules. Each myosin molecule contains a head and a tail. Tails are bundled together to form the myosin filaments while the head and some part of the tail protrudes out. k/a Cross Bridge . The myosin filament is twisted such that the successive cross bridges are present at an angle of 120 degrees, such that all directions are served. Presence of hinges in the tail and at the junction of head and tail; and ATPase activity of the head.

9. SLIDING FILAMENT MECHANISM OF MUSCLE CONTRACTION

10. Sliding Filament Mechanism of Muscle Contraction Changes in the Actin filament- The motor neuron transmits contraction signals to the muscle. The sarcoplasmic reticulum releases calcium ions into the sarcoplasm that bind w/ Troponin C This binding leads to conformational changes in the actin filament that leads to unmasking of the active site .

11. Changes in the Myosin Filament- ATP binds to the ATPase activity centre on the myosin head . The ATP is cleaved into ADP and iP but the cleaved products stay together . This leads to a conformational change that leads to the myosin head becoming upright before it binds with the actin filament . ( cocking of a spring )

12. Walk Along theory of Contraction The myosin head binds with the active site of the actin filament that causes conformational changes in the myosin molecule . The myosin head then moves away from the myosin filament dragging the actin filaments closer . After this the ADP- iP complex is released from the myosin head and the myosin heads takes back its previous position . Another ATP molecule binds to the myosin head and causes another “ power stroke ” leading to skeletal muscle contraction.

13. Types of Skeletal Muscle Contraction Isotonic - Length of the muscle fibre changes but the tension remains same. Isometric- Length of muscle fibre remains same but the tension changes. Usual contraction of the sarcomere occurs, while the in-series elastic elements (connective tissues) relax leading to a constant length.

14. Beneficial Effect When a muscle fibre is stimulated before the process of relaxation has been completed or has just been completed (efflux of calcium ions from the sarcoplasm), the muscle contraction in response to the second stimulus is of greater strength . Caused due to calcium ions that linger on , leading to a greater concentration of calcium ions in the sarcoplasm , leading to the unmasking of the active sties on the actin filaments .

15. Applied Aspects (1) Muscle fatigue- Prolonged contractions can lead to ATP depletion (myosin filaments) and the oxygen debt also leads to reduced formation of ATP. Heat rigor- Muscle proteins get coagulated leading to a state of contracture, all in response to excessively high temperatures exceeding 55 degrees Celsius. Rigor mortis- Upon death, the ATP stores of the body are depleted. The influx of calcium ions into the sarcoplasmic reticulum requires ATP. Hence contracture due to contraction of the sarcomeres occurs.

16. Applied Aspects (2) Congenital Myopathies- Defects in muscle proteins in due to genetic mutations lead to congenital myopathies. Examples include the nemaline myopathy. Duchene Muscular Dystrophy- Caused by alterations in the structure of muscle protein dystrophin because of genetic mutations leading to muscle degeneration. THANK YOU Arul Sood (1920)