1. Kip McGilliard Eastern Illinois University Lauralee Sherwood Hillar Klandorf Paul Yancey Chapter 8 Muscle Physiology Sections 8.1-8.4

2. FPO 8.1 Introduction  Muscle cells Specialized to produce force and do work Utilize a highly developed microfilament system Can shorten and develop tension Convert chemical energy of ATP into mechanical energy that can act on the environment Three types: Skeletal, cardiac and smooth

3. FPO 8.2 Skeletal Muscle

4. FPO 8.1 Introduction  Contraction of muscles permits: Purposeful locomotory movement Manipulation of external objects Propulsion of contents through hollow internal organs Emptying the contents of certain organs into the external environment Production of heat Production of sound

5. FPO 8.2 Skeletal Muscle  Skeletal muscle Makes up the muscular system Skeletal muscle cells (muscle fibers) are large (10 - 100 μm diameter), elongated and cylindrical Formed by fusion of many myoblasts during embryonic development -- have multiple nuclei Lie parallel to each other and are bundled together by connective tissue Extend the full length of the muscle

6. FPO 8.2 Skeletal Muscle  Myofibrils Specialized contractile elements Typically make up 90% of muscle volume Cylindrical intracellular organelles (1 μm diameter) extending entire length of muscle fiber The greater the density of myofibrils, the greater the force that can be generated Muscle fibers with a low percentage of myofibrils cannot generate much tension, but can contract at high frequency (e.g. mating song in cicadas) or for prolonged periods of time.

7. FPO 8.2 Skeletal Muscle

8. (a) Relationship of a whole muscle and a muscle fiber Connective tissue Muscle fiber (a single muscle cell) Tendon Muscle Figure 8-2a p337 Bundle of fibers

9. (b) Relationship of a muscle fiber and a myofibril Myofibril Dark A band Muscle fiber Light I band Figure 8-2b p337

10. (c) Cytoskeletal components of a myofibril M line Cross bridges A band Portion of myofibril H zone A bandI band Z line Titin Z line Sarcomere Thick filament Thin filament I band Figure 8-2c p337 Cross bridge Thin filament Thick filament M line

11. I bandA bandI band Cross bridge Thick filament Thin filament Fig. 8-2, p.337 Stepped Art

12. (d) Protein components of thick and thin filaments Thick filamentThin filament TropomyosinTroponin ActinMyosin head Myosin tail Fig. 8-2d, p. 197

13. FPO ANIMATION: Structure of skeletal muscle To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERECLICK HERE

14. FPO 8.2 Skeletal Muscle  Myofibrils have a regular arrangement of thick and thin filaments. Thick filaments 12 - 18 nm in diameter and 1.6 μm in length Composed of the contractile protein, myosin Tails are intertwined with globular heads projecting out at one end Each globular head has an actin binding site and an ATPase

15. FPO 8.2 Skeletal Muscle  Myofibrils have a regular arrangement of thick and thin filaments. Thin filaments 5 - 8 nm in diameter and 1.0 μm in length Composed of the contractile protein, actin Has sites for attachment to myosin Tropomyosin forms strands that cover actin binding sites when muscle is relaxed Troponin is a protein complex with three subunits One subunit binds tropomyosin, one binds actin and one can bind with Ca 2+ When not bound to Ca 2+, troponin stabilizes tropomyosin in its blocking position

16. FPO 8.2 Skeletal Muscle

17. (a) Myosin molecule 100 nm Tail Heads Myosin ATPase site Actin-binding site Figure 8-4a p339

18. (b) Thick filament Myosin molecules Cross bridges Figure 8-4b p339

19. FPO 8.2 Skeletal Muscle

20. Binding site for attachment with myosin cross bridge Thin filament Troponin Actin molecules Tropomyosin Actin helix Figure 8-5 p340

21. Actin molecules Actin helix + TroponinTropomyosin Thin filament Binding site for attachment with myosin cross bridge Fig. 8-5, p.340 Stepped Art

22. FPO 8.2 Skeletal Muscle

23. Figure 8-6a p340 Longitudinal viewCross-sectional view Tropomyosin TroponinActin Myosin cross-bridge binding site Troponin Myosin cross-bridge binding sites Myosin cross bridge Actin- binding site (a) Relaxed Myosin cross bridge Tropomyosin

24. FPO ANIMATION: Calcium and Cross Bridge Cycles To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERECLICK HERE

25. FPO 8.2 Skeletal Muscle  Basis of striations in skeletal muscle Alternating dark bands (A bands) and light bands (I bands) A band consists of a stacked set of thick filaments and portions of thin filaments that overlap them H zone (lighter area in middle of A band) has only thick filaments with no overlapping thin filaments M line (in center of A band) holds thick filaments together I band consists of thin filaments where they do not overlap with thick filaments Z line (in center of I band) is a flat cytoskeletal disc where thin filaments connect Sarcomere is the area between two Z lines Functional unit of skeletal muscle 2.5 μm in width

26. FPO 8.2 Skeletal Muscle

27. M line Sarcomere Z line I band A band H zone (a) Electron micrograph of a myofibril Figure 8-3a p338

28. Figure 8-3b p338

29. FPO 8.3 Molecular Basis of Skeletal Muscle Contraction  Sliding filament mechanism of muscle contraction During contraction, thin filaments slide toward the center of the A band, resulting in shortening of the sarcomere. Neither thick nor thin filaments change length Mechanism applies to both vertebrate and nonvertebrate striated muscle

30. FPO 8.3 Molecular Basis of Skeletal Muscle Contraction

31. Thin filament A band same width H zone shorter A bandH zone Contracted Relaxed Sarcomere I band shorter Sarcomere shorter Thick filament Z lineI bandZ line Figure 8-7 p341

32. FPO ANIMATION: Muscle Contractions To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERECLICK HERE

33. FPO 8.3 Molecular Basis of Skeletal Muscle Contraction  Cross-bridge cycling Occurs during muscle contraction when Ca 2+ binds to troponin, troponin changes shape and binding sites on actin are uncovered Myosin globular heads (cross-bridges) bind to actin Cross-bridge bends 45º inward, pulling thin filament with it (power stroke) Myosin detaches from actin and returns to its original conformation, attaching to a new site on actin Complete shortening is accomplished by repeated cross-bridge cycles

34. FPO 8.3 Molecular Basis of Skeletal Muscle Contraction

35. (a) Single cross-bridge cycle 4) Binding: Cross bridge binds to more distal actin molecule; cycle repeats. 2) Power stroke: Cross bridge bends, pulling thin myofilament inward. 1) Binding: Myosin cross bridge binds to actin molecule. Z line Myosin cross bridge Actin molecules in thin myofilament 3) Detachment: Cross bridge detaches at end of power stroke and returns to original conformation. Figure 8-8a p342

36. Figure 8-8c p342 Thin myofilamentThick myofilament (c) Simultaneous pulling inward of all six thin filaments surrounding a thick filament

37. FPO 8.3 Molecular Basis of Skeletal Muscle Contraction  Ca 2+ is the link between excitation and contraction Skeletal muscles are stimulated to contract by release of acetylcholine (ACh) at neuromuscular junctions Resulting action potential is conducted along the muscle cell membrane Surface membrane dips deeply into the muscle fiber to form a transverse tubule (T tubule) Action potential enters the interior of the muscle fiber along the T tubules Induces permeability changes in the adjacent sarcoplasmic reticulum

38. FPO 8.3 Molecular Basis of Skeletal Muscle Contraction

39. I band A band Transverse (T) tubule Segments of sarcoplasmic reticulum Surface membrane of muscle fiber Myofibrils Lateral Sacs (Terminal cisternae) I band Figure 8-9 p343

40. FPO 8.3 Molecular Basis of Skeletal Muscle Contraction  Ca 2+ is the link between excitation and contraction Ca 2+ is stored in the lateral sacs of the sarcoplasmic reticulum Action potential in T tubule triggers release of Ca 2+ from sarcoplasmic reticulum into the cytosol Elevated cytosolic Ca 2+ results in increased binding of Ca 2+ to troponin, initiating contraction During relaxation, Ca 2+ is pumped back into the sarcoplasmic reticulum by Ca 2+ -ATPase pumps, reducing cytosolic Ca 2+ levels

41. FPO 8.3 Molecular Basis of Skeletal Muscle Contraction

42. Troponin Myosin cross- bridge binding Motor end plate Terminal button T tubule Lateral sac of sarcoplasmic reticulum Cycle repeats Acetylcholine-gated receptor-channel for cations Neuromuscular junction Actin molecule Myosin cross bridge Thin filament Thick filament Acetylcholine Plasma membrane of muscle cell Ca2+ pump Ca2+-release channel Ca2+-release channel Tropomyosin Actin-binding site Figure 8-11 p345

43. FPO ANIMATION: Action Potential and Muscle Contractions To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERECLICK HERE

44. FPO 8.3 Molecular Basis of Skeletal Muscle Contraction  ATP powers cross-bridge cycling Myosin ATPase on thick filaments splits ATP to form adenosine diphosphate (ADP) and inorganic phosphate (P i ) ADP and P i remain attached to myosin, energizing it During and after the subsequent power stroke, P i and ADP are released Myosin ATPase site attaches a new ATP molecule Attachment of new ATP permits detachment of the cross bridge, setting up for another power stroke

45. FPO 8.3 Molecular Basis of Skeletal Muscle Contraction

46. ...or... No Ca2+ Fresh ATP available No ATP (after death)...or... Cross- bridge cycle Energy present (excitation) Energy 1 2a 3 4a 2b 4b Figure 8-12 p346 Resting Energized Detachment Binding Bending Rigor complex

47. No ATP (after death) 4b Rigor complex 4aDetachment2aBinding1 Energized 2b Resting 3 Bending (powerstroke) Fig. 8-12, p.346 Stepped Art

48. FPO 8.3 Molecular Basis of Skeletal Muscle Contraction  Contractile activity outlasts the action potential that created it A single action potential lasts 1 - 2 msec Produces a muscle contraction (twitch) after a short latent period Contraction time averages 50 msec Contraction continues until completion of Ca 2+ release Relaxation time is slightly longer Relaxation occurs as Ca 2+ is pumped back into the sarcoplasmic reticulum Total twitch time is about 100 msec

49. FPO 8.3 Molecular Basis of Skeletal Muscle Contraction

50. FPO 8.4 Skeletal Muscle Mechanics  Muscle structure In vertebrates, tendons attach muscle to bones In arthropods, muscles attach to ridges that project from the inner face of the exoskeleton (apodemes) Muscles are arranged in antagonistic pairs Flexors bend a limb (e.g. biceps) Extensors straighten the limb (e.g. triceps)

51. FPO 8.4 Skeletal Muscle Mechanics  Motor units A single action potential in a muscle fiber produces an all-or-none contraction Each vertebrate muscle fiber is supplied by only one motor neuron Each motor neuron branches and innervates many muscle fibers All of the muscle fibers innervated by one motor neuron will contract simultaneously, forming a motor unit

52. FPO 8.4 Skeletal Muscle Mechanics

53. FPO 8.4 Skeletal Muscle Mechanics  Motor units To produce stronger muscle contractions, more motor units are stimulated to contract (motor unit recruitment) Muscles that provide precise, delicate movements have few muscle fibers per motor unit (e.g. external eye muscles) Muscles used for powerful, coarsely controlled movement have many muscle fibers per motor unit (e.g. leg muscles) Asynchronous recruitment of motor units is coordinated by the brain to prevent fatigue

54. FPO 8.4 Skeletal Muscle Mechanics

55. Figure 8-15a p351

56. Figure 8-15b p351

57. FPO 8.4 Skeletal Muscle Mechanics  Repetitive stimulation of muscle fibers If a muscle fiber is stimulated before it relaxes from a previous stimulus, the second contraction is added to the first (twitch summation). This happens because the duration of the muscle contraction is much longer than the duration of the action potential. Factors contributing to twitch summation Sustained elevation of cytosolic Ca 2+ More time to stretch the series-elastic component (e.g. tendons) allows a stronger recoil

58. FPO 8.4 Skeletal Muscle Mechanics  Repetitive stimulation of muscle fibers If a muscle fiber is stimulated so rapidly that it has no chance to relax at all between stimuli, a smooth sustained contraction occurs (tetanus). Graded muscle contractions are produced by controlling the number of motor units stimulated and the frequency of their stimulation. Tetanic contractions and asynchronous motor unit recruitment are used in normal physiological motor control.

59. FPO 8.4 Skeletal Muscle Mechanics

60. If a muscle fiber is stimulated so rapidly that it does not have an opportunity to relax at all between stimuli, a maximal sustained contraction known as tetanus occurs. If a muscle fiber is restimulated before it has completely relaxed, the second twitch is added on to the first twitch, resulting in summation. If a muscle fiber is restimulated after it has completely relaxed, the second twitch has the same magnitude as the first twitch. (b) Twitch summation(a) No summation Stimulation ceases or fatigue begins Tetanus Twitch summation Single twitch –90 Action potentials Contractile activity (c) Tetanus Membrane potential (mV) Relative tension 3 2 1 0 0 +30 Time Figure 8-16 p352

61. FPO 8.4 Skeletal Muscle Mechanics  Control of arthropod muscle tension Nervous system of nonvertebrates contains relatively few neurons Muscle fibers are innervated by more than one motor neuron and many neuromuscular junctions (multiterminal innervation). Graded depolarization produces graded contraction of muscle fibers Presynaptic inhibition and postsynaptic inhibition (IPSPs) modulate contraction strength

62. FPO 8.4 Skeletal Muscle Mechanics  Length-tension relationship Every muscle has an optimal length ( l o ) at which maximal force can be achieved upon tetanic contraction Explained by the sliding-filament mechanism Maximum tension is achieved when the maximal number of cross-bridge sites are accessible to actin for binding Muscles are usually stretched to their l o by normal attachment to the skeleton

63. FPO 8.4 Skeletal Muscle Mechanics

64. 70% 100% 130% 170% Range of length changes that can occur in the body D Percent maximal (tetanic) tension Shortened muscle Stretched muscle Muscle fiber length compared with resting length 50% 100% (resting muscle length) I0I0 C A B Figure 8-17 p354

65. FPO 8.4 Skeletal Muscle Mechanics  Transmission of muscle tension to the skeleton Muscle tension is transmitted to the skeleton (or exoskeleton) by tightening the series-elastic components A skeletal muscle is typically attached to two bones When a muscle shortens one bone moves in relation to the other The end of the muscle attached to the more stationary part of the skeleton is the origin The end attached to the more movable part is the insertion

66. FPO 8.4 Skeletal Muscle Mechanics

67. Figure 8-18 p355 Biceps Contractile component (sarcomeres) Series-elastic component (titin connective tissue/tendon) Load Triceps Load

68. FPO 8.4 Skeletal Muscle Mechanics  For a muscle to shorten during contraction, the tension must exceed the forces that oppose movement (load) Isotonic contraction Muscle shortens Muscle tension remains constant Work is done (work = force x distance) Isometric contraction Muscle is prevented from shortening Tension develops at constant muscle length No work is done Eccentric contraction Muscle lengthens during contraction because it is being stretched by an external force

69. FPO 8.4 Skeletal Muscle Mechanics  Load-velocity relationship The greater the load, the lower the velocity of shortening Velocity falls to zero when the load exceeds tension (isometric contraction)

70. FPO 8.4 Skeletal Muscle Mechanics  Hydrostatic skeleton A pressurized moving fluid can create large-scale movement Contraction of circular muscles surrounding a closed chamber of body fluid stiffens the body region around it Longitudinal muscles shorten the chamber upon contraction and lengthen it when relaxed Examples: Sea anemone, earthworm, octopus, elephant’s trunk

71. FPO 8.4 Skeletal Muscle Mechanics  Levers A lever is a rigid structure capable of moving around a pivot point (fulcrum) Bones are levers and joints are fulcrums The power arm is the part of a lever between the fulcrum and the point where an upward force is applied The load arm is the part between the fulcrum and the downward force exerted by the load The lever system of the elbow joint amplifies movements of the biceps into larger, more rapid movements of the hand

72. FPO 8.4 Skeletal Muscle Mechanics

73. Figure 8-20b p358 Upward applied muscle force = 35 kg Velocity of muscle shortening = 1 cm/unit of time 5 kg Insertion of biceps Biceps Distance moved by hand = 7 cm Distance moved by muscle = 1 cm 5 kg Hand velocity = 7 cm/unit of time Fulcrum for lever Power arm of lever = 5 cm Downward force of load = 5 kg Load arm of lever = 35 cm Lever ratio 1: 7 (5 cm : 35 cm) (b) Flexion of elbow joint as example of body lever action

74. FPO ANIMATION: Opposing muscle action To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERECLICK HERE

75. FPO 8.4 Skeletal Muscle Mechanics  Elastic springlike mechanisms Store muscle-generated energy Resilin is a highly elastic protein made of coiled peptide chains stabilized by cross-linked tyrosines (e.g. in jumping fleas) Provide rapid locomotion Resilin springs aid rapid wing beats of some insects Increase energy efficiency While running or hopping, energy of gravity is captured by tendons which rebound when the leg pushes off (e.g. hopping kangaroo)