1. drnnkumari 18-11-11 1 MBBS, Batch 16 MCBM, Lect. 25 Mechanism of muscle contraction & relaxation

2. drnnkumari 18-11-11 2 Learning Objectives of this lesson are to Describe the mechanism of muscle contraction and relaxation Explain what is Excitation-contraction coupling Length –Tension relationship Types of contractions Rigor mortis

3. drnnkumari 18-11-11 3 Learning outcomes At the end of this lecture the students should be able to 1.Define excitation contraction coupling 2.Describe the molecular mechanism of contraction and relaxation 3.Describe the sliding filament theory of muscle contraction 4.Describe the role of regulatory proteins and calcium in muscle contraction 5.Briefly describe the relation ship between length and tension in skeletal muscle. 6.Briefly describe how forces generated by contraction of sarcomere transmitted o result in muscle shortening. 7.Define isometric contraction & isotonic contraction. What are the fundamental differences between these two types of muscle contractions. 8.What is the physiologic mechanism of rigor mortis?

4. drnnkumari 18-11-11 4 Sarcotubular system – A membranous structure around the muscle fibril It consists of T system of transverse tubules continuous with sarcolemma. Its function is rapid transmission of action potential from the cell membrane to all the fibrils Sarcoplamic reticulum has 2 enlarged terminal cisterns in close contact with T- tubules at the junction between A& I band. In the cardiac muscle T-tubule is present near the Z line Cisternae contain Ca 2+.Function of sarcoplasmic reticulum is to move Ca 2+ & muscle metabolism

5. drnnkumari 18-11-11 5 Molecular structure of the muscle

6. drnnkumari 18-11-11 6 ….…. sarcolemma sarcoplasmic reticulum Triad T-tubule A band Sarcomere Z lineMyosin Actin Terminal cisternae Skeletal muscle ∩ ∩

7. drnnkumari 18-11-11 7 Molecular basis of contraction. The sliding filament Theory A.Steps in contraction: 1. Discharge of motor neuron 2. Release of transmitter at motor end plate 3. Binding of acetylcholine to nicotinic acetylcholine receptors 4.Increased Na + & K + conductance in end plate membrane 5.Generation of end plate potential

8. drnnkumari 18-11-11 8 6. Generation of muscle action potential 7. Inward spread of depolarization along T- tubules. 8. Release of Ca 2+ from terminal cisterns of sarcoplasmic reticulum & diffusion to thick & thin filaments In resting muscle, troponin I is tightly bound to actin, tropomyosin covers the sites where myosin heads bind to actin. Troponin- tropomyosin complex forms a relaxing protein that inhibit interaction between actin & myosin.

9. drnnkumari 18-11-11 9 9. When Ca 2+ binds to troponin C, the binding of troponin I to actin is weakened uncovering & this permits the tropomyosin to move laterally. This movement uncovers binding sites for the myosin heads. 10. Formation of cross-linkages between actin & myosin ATP is then splits & sliding of thin on thick filaments, producing movement. Steps in relaxation Ca 2+ pumped back into sarcoplasmic reticulum Release of Ca 2+ from troponin Cessation of interaction between actin & myosin

10. drnnkumari 18-11-11 10 Define excitation contraction coupling The process by which depolarization of the muscle membrane initiates contraction is called excitation- contraction coupling.

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14. drnnkumari 18-11-11 14 Activation by nerve causes myosin heads (cross bridges) to attach to binding sites on the thin filament Myosin heads then bind to the next site of the thin filament The Sliding Filament Theory of Muscle Contraction

15. drnnkumari 18-11-11 15 Sarcomere at rest Sarcomere during contraction Sarcomere during relaxation Ca 2+ is actively pumped back into the longitudinal portions of the sarcoplasmic reticulum & diffuses into the cistern. Release of Ca 2+ from terminal cisternae of the sarcoplasmic reticulum Ca 2+ diffuses towards the myofilaments & initiate the process of contraction Ca 2+ ions are stored in the terminal cisternae

16. drnnkumari 18-11-11 16 Length-tension relationship for the human triceps muscle. The passive tension curve measures the tension exerted by this skeletal muscle at each length when it is not stimulated. The total tension curve represents the tension developed when the muscle contracts isometrically in response to a maximal stimulus. The active tension is the difference between the two. Relation Between Muscle Length, Tension, & Velocity of Contraction

17. drnnkumari 18-11-11 17 THE LENGTH-TENSION RELATIONSHIP The muscle is stretched: passive tension increases active (twitch) tension is maximum at L o activepassive LoLo Tension Length The variation of active force can be explained by the degree of actin/myosin overlap - the sliding-filament hypothesis

18. drnnkumari 18-11-11 18 When the muscle fiber contracts isometrically, the tension developed is proportionate to the number of cross-linkages between the actin and the myosin molecules. When muscle is stretched, the overlap between actin and myosin is reduced and the number of cross linkages is therefore reduced. When the muscle is appreciably shorter than resting length, the distance the thin filaments can move is reduced

19. drnnkumari 18-11-11 19 The velocity of muscle contraction varies inversely with the load on the muscle. At a given load, the velocity is maximal at the resting length and declines if the muscle is shorter or longer than this length.

20. drnnkumari 18-11-11 20 Types of muscle contraction: Isotonic:- In this type of contraction the length of the muscle changes but the tension remains constant Eg. Lifting the bucket from the ground level Isometric:- In this type the length remains the same but the tension increases. Eg. Trying to lift a car or trying to push the wall.

21. drnnkumari 18-11-11 21 Contracture is a state of prolonged reversible shortening of muscle It may be due to fatigue, excessive excitation of chemical actions. If the return of Ca 2 + into the sarcoplasmic reticulum is inhibited, the myosin & actin do not separate & relaxation does not occur

22. drnnkumari 18-11-11 22 Rigor Mortis ( Post mortem rigidity) After death there is stiffening of the corpse, This phenomenon which is called rigor mortis. It is due mainly to the changes under gone by the muscles. The muscles lose Extensibility & excitability Become shorter & more opaque Glycogen & ATP are depleted Accumulation of lactic acid & acid phosphate Coagulation of muscle proteins causes loss of extensibility & stiffening of muscle

23. drnnkumari 18-11-11 23 ATP is required for separation of actin & myosin cross linkages. Since ATP is depleted, the muscle remain in a contracted state. The state of rigor persists until the proteins are destroyed by bacterial putrefaction. After the rigor passes off the muscles are relaxed. This is due to autolysis or self digestion of muscles by the intracellular enzymes which act in acid medium. Cause of Rigor Mortis