1. Skeletal muscle physiology Dr. shafali Singh

2. Skeletal muscle physiology introduction ■ THE ROLES OF MUSCLE ■ THE FUNCTIONAL ANATOMY AND ULTRASTRUCTURE OF MUSCLE ■ THE ACTIVATION AND INTERNAL CONTROL OF MUSCLE FUNCTION ■ ENERGY SOURCES FOR MUSCLE CONTRACTION

3. THE ROLES OF MUSCLE Muscle tissue familiar functions include moving, speaking, and a host of other everyday actions. Less familiar, but no less important, are the internal functions of muscle. It pumps our blood and regulates its flow, it moves our food as it is being digested and causes the expulsion of wastes, and it serves as a critical regulator of numerous internal processes.

4. THE FUNCTIONAL ANATOMY AND ULTRASTRUCTURE OF MUSCLE Skeletal muscle morphology Muscle filaments and their arrangement Cytoskeletal proteins Sarcotubular system

5. Skeletal muscle morphology Each muscle fiber is a cell of skeletal muscle.

8. MUSCLE FILAMENTS Each muscle fiber or filament behaves as a single unit i.e. a cell, is multinucleate, and contains myofibrils. The myofibrils are surrounded sarcoplasmic reticulum and are invaginated by transverse tubules (T tubules). Each myofibril contains interdigitating thick and thin filaments, which are arranged longitudinally and cross-sectionally in sarcomeres. The repeating units sarcomeres account for the unique banding pattern seen in striated muscle (which includes both skeletal and cardiac muscles)

15. Skeletal and cardiac muscle, which are both striated, at resting length contain in each sarcomere an A band. This “A “ band contains: A. essentially all the contractile protein myosin, but no actin. B. Essentially all the contractile protein actin, but no myosin. C. essentially all the myosin, plus some actin. D. essentially all the actin, plus some myosin. E. troponin and tropomyosin, but no actin. Question

16. The assembly of the thin (actin) filaments of skeletal muscle.

19. Troponin is a complex of three globular proteins (troponin T, troponin I, and troponin C) located at regular intervals along the tropomyosin filaments. Troponin T (T for tropomyosin) attaches the troponin complex to tropomyosin. Troponis I (I for inhibition), along with tropomyosin, inhibits the interaction of actin and myosin by covering the myosin- binding site on actin. Troponin C (C for Ca2+) is a Ca2+-binding protein. Ca2+ binding to troponin C produces a conformational change in the troponin complex. This conformational change moves tropomyosin out of the way, permitting the binding of actin to the myosin heads.

21. The assembly of skeletal muscle thick filaments from myosin molecules

23. Cytoskeletal Proteins Titin, Nebulin, alpha-actinin, Dystrophin,

24. Lies just inside the sarcolemma, participates in the transfer of force from the contractile system to the outside of the cells via membrane- spanning proteins called integrins. External to the cells, the protein laminin forms a link between integrins and the extracellular matrix. These proteins are disrupted in the group of genetic dis-eases collectively called muscular dystrophy, and their lack or malfunction leads to muscle degeneration and weakness and death.

26. Skeletal Muscle Membrane Systems.

27. SARCOTUBULAR SYSTEM

28. The transverse (T) tubules are an extensive network of muscle cell membrane (sarcolemmal membrane) that invaginates deep into the muscle fiber. The T tubules are responsible for carrying depolarization from action potentials at the muscle surface to the interior of the fiber. The T tubules make contact with the terminal cisternae of the sarcoplasmic reticulum and contain a voltage-sensitive protein called the dihydropyridine receptor.

30. The terminal cisternae of the sarcoplasmic reticulum make contact with T tubules in a triad arrangement. The sarcoplasmic reticulum contains ryanodine receptor which is a Ca release channel. Ca2+ is accumulated in the sarcoplasmic reticulum by the action of Ca2+ ATPase (SERCA) in the sarcoplasmic reticulum membrane. Within the sarcoplasmic reticulum, Ca is bound to calsequestrin, a low-affinity, high-capacity Ca2+- binding protein.

33. Q The major immediate source of calcium for the initiation of skeletal muscle contraction is (A) Calcium entry through the sarcolemma during the passage of an action potential (B) A rapid release of calcium from its storage sites in the T tubules (C) A rapid release of calcium from the terminal cisternae of the sarcoplasmic reticulum (D) A release of calcium that is bound to cytoplasmic proteins in the region of the myofilaments

34. Excitation-Contraction Coupling Links Electrical and Mechanical Events

35. Steps involved in excitation-contraction coupling Action potentials from the muscle cell membrane are propagated to the T tubules by the spread of local currents. The T tubules are continuous with the sarcolemmal membrane and carry the depolarization from the surface to the interior of the muscle fiber. Depolarization of the T tubules causes a critical conformational change in its voltage-sensitive dihydropyridine-receptor. This conformational change opens the Ca2+-release channels at ryanodine receptors on the nearby sarcoplasmic reticulum.

37. Excitation-contraction coupling in skeletal muscle Temporal relationships between an action potential in the skeletal muscle fiber, the subsequent in intracellular free Ca2+ concentration (which is released from the sarcoplasmic reticulum), and contraction of the muscle fiber

38. Ca2+ is released from its storage site in the sarcoplasmic reticulum ICF of the muscle fiber, resulting in an increase in intracellular Ca2+ concentration. Ca2+ binds to troponin C on the thin filaments, causing a conformational change in the troponin complex. Troponin C can bind as many as four Ca2+ ions per molecule of protein. This Ca binding is cooperative. So, each molecule bound Ca2+ increases the affinity of troponin C for the next Ca2+. The conformational change in troponin causes tropomyosin (which was previously blocking the interaction and myosin) to be moved out of the way so that cross-bridge cycling can begin. Cross-bridge cycling: Formation of cross-bridges is associated with hydrolysis of ATP and generation of force.

39. Q Calcium ions are required for the normal activation of all muscle types. Which statement below most closely describes the role of calcium ions in the control of skeletal muscle contraction? (A) The binding of calcium ions to the thick filament regulatory proteins activates the enzymatic activity of the myosin molecules (B) The binding of calcium ions to regulatory proteins on the thin filaments removes the inhibition of actin-myosin interaction (C) Calcium ions serve as an inhibitor of the interaction of thick and thin filaments (D) A high concentration of calcium ions in the myofilament space is required to maintain muscle in a relaxed state.

40. Sequences in cross-bridge cycle Attachment of thick-filament to sites along the thin filaments, Production of a mechanical movement, Crossbridge detachment from the thin filaments, and Subsequent reattachment of the cross-bridges at different sites along the thin filaments

41. Cross-Bridge Cycling- Sarcomere Shortening

44. Relaxation occurs when Ca2+ is reaccumulated in the sarcoplasmic reticulum by the Ca2+ ATPase of the sarcoplasmic reticulum membrane (SERCA). Ca2+ is released from troponin C and tropomyosin returns to its position, where it blocks the myosin-binding site on actin. As long as the intracellular Ca2+ is low, cross-bridge cannot occur, and the muscle will be relaxed.

46. Q The normal process of relaxation in skeletal muscle depends on (A) A sudden reduction in the amount of ATP available for the crossbridge interactions (B) Metabolically supported pumping of calcium out of the cells when the membrane potential repolarizes (C) A rapid reuptake of calcium into the sarcoplasmic reticulum (D) An external force to separate the interacting myofilaments

47. Q In the absence of an adequate supply of ATP for skeletal muscle contraction, (A) Myofilament interaction ceases, and the muscle relaxes (B) Actin and myosin filaments cannot separate, and the muscle stiffens (C) Creatine phosphate can directly support myofilament interaction, although less efficiently (D) The lower energy form, ADP, can support contraction at a reduced rate

48. Q The compound ATP provides the energy for muscle contraction during the crossbridge cycle. A second important function for ATP in the cycle is to (A) Provide the energy for relaxation (B) Allow the thick and thin filaments to detach from each other during the cross bridge cycle (C) Maintain the separation of thick and thin filaments when the muscle is at rest (D) Promote the binding of calcium ions to the regulatory proteins

49. The cross-bridge cycling mechanism just described is called the sliding filament theory because the myosin cross-bridge is pulling the actin thin filament toward the center of the sarcomere, thereby resulting in an apparent "sliding" of the thin filament past the thick filament.

50. The Sliding Filament Theory of Muscle Contraction Slide 6.17a Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings  Activation by nerve causes myosin heads to attach to binding sites on the thin filament  Myosin heads then bind to the next site of the thin filament Figure 6.7

51. The Sliding Filament Theory of Muscle Contraction Slide 6.17b Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings  This continued action causes a sliding of the myosin along the actin  The result is that the muscle is shortened (contracted) Figure 6.7

53. Sarcomere Relaxed Sarcomere Partially Contracted Sarcomere Fully Contracted

55. Sample question During excitation-contraction coupling, which of the bands shown in the above electron micrograph remains constant in length? a.A band b.I band c.H band d.Sarcomere

56. Q During the shortening of skeletal muscle, (A) The distance between Z lines stays the same (B) The width of the I band changes (C) The width of the A band changes (D) All internal spacings between repeating structures change proportionately

57. The crossbridges are the sites where force and shortening are produced and where the chemical energy stored in the muscle is transformed into mechanical energy.

58. The multiplying effect of sarcomeres placed in series.

60. The effects of sarcomere length on force generation

61. Q When an isolated skeletal muscle is stretched beyond its optimal length (but not to the point where damage occurs), the reduction in contractile force is due to (A) Lengthening of the myofilaments so that crossbridges become spaced farther apart and can interact less readily (B) Decreased overlap between thick and thin filaments, which reduces the number of crossbridges that interact (C) The thinning of the muscle, which reduces its cross- sectional area and, hence, the force that it can produce (D) A proportional reduction in the amount of calcium released from the sarcoplasmic reticulum