1. Chapter 8 Muscle Physiology

2. Outline Structure Contractile mechanisms Mechanics Control Other muscle types –Smooth, cardiac

3. Outline Structure –Muscle fiber (from myoblasts) –Myofibrils –Thick and thin filaments (actin and myosin) –A,H,M,I,Z –Sarcomere –Titin –elasticity –Cross bridges –Myosin, Actin, tropomyosin, troponin

4. Muscle Comprises largest group of tissues in body Three types of muscle –Skeletal muscle Make up muscular system –Cardiac muscle Found only in the heart –Smooth muscle Appears throughout the body systems as components of hollow organs and tubes Classified in two different ways –Striated or unstriated –Voluntary or involuntary

5. Striated muscle Unstriated muscle Cardiac muscle Voluntary muscle Involuntary muscle Skeletal muscleSmooth muscle Fig. 8-1, p. 259

6. Muscle Controlled muscle contraction allows –Purposeful movement of the whole body or parts of the body –Manipulation of external objects –Propulsion of contents through various hollow internal organs –Emptying of contents of certain organs to external environment

7. Structure of Skeletal Muscle Muscle consists a number of muscle fibers lying parallel to one another and held together by connective tissue Single skeletal muscle cell is known as a muscle fiber –Multinucleated –Large, elongated, and cylindrically shaped –Fibers usually extend entire length of muscle

8. Fig. 8-2a, p. 260 (a) Relationship of a whole muscle and a muscle fiber Connective tissue Muscle fiber (a single muscle cell) Tendon Muscle

9. Structure of Skeletal Muscle Myofibrils –Contractile elements of muscle fiber –Regular arrangement of thick and thin filaments Thick filaments – myosin (protein) Thin filaments – actin (protein) –Viewed microscopically myofibril displays alternating dark (the A bands) and light bands (the I bands) giving appearance of striations

10. Fig. 8-2b, p. 260 (b) Relationship of a muscle fiber and a myofibril Myofibril Dark A band Muscle fiber Light I band

11. Structure of Skeletal Muscle Sarcomere –Functional unit of skeletal muscle –Found between two Z lines (connects thin filaments of two adjoining sarcomeres) –Regions of sarcomere A band –Made up of thick filaments along with portions of thin filaments that overlap on both ends of thick filaments H zone –Lighter area within middle of A band where thin filaments do not reach M line –Extends vertically down middle of A band within center of H zone I band –Consists of remaining portion of thin filaments that do not project into A band

12. Fig. 8-2c, p. 260 (c) Cytoskeletal components of a myofibril M line Cross bridges I band Portion of myofibril H zone A bandI band Z lineM line Z line Sarcomere Thick filament Thin filament A band Cross bridge Thin filament Thick filament

13. Structure of Skeletal Muscle Titin –Giant, highly elastic protein –Largest protein in body –Extends in both directions from M line along length of thick filament to Z lines at opposite ends of sarcomere –Two important roles: Along with M-line proteins helps stabilize position of thick filaments in relation to thin filaments Greatly augments muscle’s elasticity by acting like a spring

14. Myosin Component of thick filament Protein molecule consisting of two identical subunits shaped somewhat like a golf club –Tail ends are intertwined around each other –Globular heads project out at one end Tails oriented toward center of filament and globular heads protrude outward at regular intervals –Heads form cross bridges between thick and thin filaments Cross bridge has two important sites critical to contractile process –An actin-binding site –A myosin ATPase (ATP-splitting) site

15. Structure and Arrangement of Myosin Molecules Within Thick Filament

16. Actin Primary structural component of thin filaments Spherical in shape Thin filament also has two other proteins –Tropomyosin and troponin Each actin molecule has special binding site for attachment with myosin cross bridge –Binding results in contraction of muscle fiber

17. Fig. 8-5, p. 263 Binding site for attachment with myosin cross bridge Thin filament Troponin Actin molecules Tropomyosin Actin helix

18. Actin and myosin are often called contractile proteins. Neither actually contracts. Actin and myosin are not unique to muscle cells, but are more abundant and more highly organized in muscle cells.

19. Tropomyosin and Troponin Often called regulatory proteins Tropomyosin –Thread-like molecules that lie end to end alongside groove of actin spiral –In this position, covers actin sites blocking interaction that leads to muscle contraction Troponin –Made of three polypeptide units One binds to tropomyosin One binds to actin One can bind with Ca 2+

20. Tropomyosin and Troponin Troponin –When not bound to Ca 2+, troponin stabilizes tropomyosin in blocking position over actin’s cross-bridge binding sites –When Ca 2+ binds to troponin, tropomyosin moves away from blocking position –With tropomyosin out of way, actin and myosin bind, interact at cross-bridges –Muscle contraction results

21. (a) Relaxed Myosin cross-bridge binding sites Myosin cross bridge Tropomyosin TroponinActin Actin-binding site (b) Excited

22. Cross-bridge interaction between actin and myosin brings about muscle contraction by means of the sliding filament mechanism.

23. Outline Contractile mechanisms Sliding filament mechanism (Theory) –Ca dependence –Power stroke –T tubules –Ca release Lateral sacs, foot proteins, ryanodine receptors, dihydropyradine receptors –Cross bridge cycling Rigor mortis, relaxation, latent period

24. Sliding Filament Mechanism Increase in Ca 2+ starts filament sliding Decrease in Ca 2+ turns off sliding process Thin filaments on each side of sarcomere slide inward over stationary thick filaments toward center of A band during contraction As thin filaments slide inward, they pull Z lines closer together Sarcomere shortens

25. Fig. 8-8, p. 265 Basic 4 steps

26. Transverse Tubules T tubules Run perpendicularly from surface of muscle cell membrane into central portions of the muscle fiber Since membrane is continuous with surface membrane – action potential on surface membrane also spreads down into T-tubule Spread of action potential down a T tubule triggers release of Ca 2+ from sarcoplasmic reticulum into cytosol

27. Fig. 8-9, p. 266 I band A band Transverse (T) tubule Segments of sarcoplasmic reticulum Surface membrane of muscle fiber Myofibrils Lateral sacs I band

28. Sarcoplasmic Reticulum Modified endoplasmic reticulum Consists of fine network of interconnected compartments that surround each myofibril Not continuous but encircles myofibril throughout its length Segments are wrapped around each A band and each I band –Ends of segments expand to form saclike regions – lateral sacs (terminal cisternae)

29. 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 Fig. 8-11, p. 268 12 3 4 56 7 8

30. ...or... No Ca2+ Fresh ATP available No ATP (after death)...or... Cross- bridge cycle present (excitation) Energized Resting Binding Detachment Bending Rigor complex 1 2a 3 4b 2b 4a Fig. 8-12, p. 269

31. Power Stroke Activated cross bridge bends toward center of thick filament, “rowing” in thin filament to which it is attached Sarcoplasmic reticulum releases Ca 2+ into sarcoplasm Myosin heads bind to actin Myosin heads swivel toward center of sarcomere (power stroke) ATP binds to myosin head and detaches it from actin

32. Power Stroke Hydrolysis of ATP transfers energy to myosin head and reorients it Contraction continues if ATP is available and Ca 2+ level in sarcoplasm is high

33. Sliding Filament Mechanism All sarcomeres throughout muscle fiber’s length shorten simultaneously Contraction is accomplished by thin filaments from opposite sides of each sarcomere sliding closer together between thick filaments

34. Relaxation Depends on reuptake of Ca 2+ into sarcoplasmic reticulum (SR) Acetylcholinesterase breaks down ACh at neuromuscular junction Muscle fiber action potential stops When local action potential is no longer present, Ca 2+ moves back into sarcoplasmic reticulum

35. Outline Mechanics –Tendons –Twitch –Motor unit –Motor unit recruitment –Fatigue –Asynchronous recruitment –Twitch, tetanus, summation –Muscle length, isometric, isotonic Tension, origin, insertion

36. Skeletal Muscle Mechanics Muscle consists of groups of muscle fibers bundled together and attached to bones Connective tissue covering muscle divides muscle internally into bundles Connective tissue extends beyond ends of muscle to form tendons –Tendons attach muscle to bone

37. Muscle Contractions Contractions of whole muscle can be of varying strength Twitch –Brief, weak contraction –Produced from single action potential –Too short and too weak to be useful –Normally does not take place in body Two primary factors which can be adjusted to accomplish gradation of whole-muscle tension –Number of muscle fibers contracting within a muscle –Tension developed by each contracting fiber

38. Motor Unit Recruitment Motor unit –One motor neuron and the muscle fibers it innervates Number of muscle fibers varies among different motor units Number of muscle fibers per motor unit and number of motor units per muscle vary widely –Muscles that produce precise, delicate movements contain fewer fibers per motor unit –Muscles performing powerful, coarsely controlled movement have larger number of fibers per motor unit

39. Motor Unit Recruitment Asynchronous recruitment of motor units helps delay or prevent fatigue Factors influencing extent to which tension can be developed –Frequency of stimulation –Length of fiber at onset of contraction –Extent of fatigue –Thickness of fiber

40. Motor neuron Spinal cord Muscle fiber = Motor unit 1 = Motor unit 2 = Motor unit 3 KEY Fig. 8-18, p. 274

41. Twitch Summation and Tetanus Twitch summation –Results from sustained elevation of cytosolic calcium Tetanus –Occurs if muscle fiber is stimulated so rapidly that it does not have a chance to relax between stimuli –Contraction is usually three to four times stronger than a single twitch

42. 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 Fig. 8-20, p. 276

43. Muscle Tension Tension is produced internally within sarcomeres Tension must be transmitted to bone by means of connective tissue and tendons before bone can be moved (series-elastic component) Muscle typically attached to at least two different bones across a joint –Origin End of muscle attached to more stationary part of skeleton –Insertion End of muscle attached to skeletal part that moves

44. 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 Fig. 8-21, p. 277

45. Types of Contraction Two primary types –Isotonic Muscle tension remains constant as muscle changes length –Isometric Muscle is prevented from shortening Tension develops at constant muscle length

46. Contraction-Relaxation Steps Requiring ATP Splitting of ATP by myosin ATPase provides energy for power stroke of cross bridge Binding of fresh molecule of ATP to myosin lets bridge detach from actin filament at end of power stroke so cycle can be repeated Active transport of Ca 2+ back into sarcoplasmic reticulum during relaxation depends on energy derived from breakdown of ATP

47. Energy Sources for Contraction Transfer of high-energy phosphate from creatine phosphate to ADP –First energy storehouse tapped at onset of contractile activity Oxidative phosphorylation (citric acid cycle and electron transport system –Takes place within muscle mitochondria if sufficient O 2 is present Glycolysis –Supports anaerobic or high-intensity exercise

48. Muscle Fatigue Occurs when exercising muscle can no longer respond to stimulation with same degree of contractile activity Defense mechanism that protects muscle from reaching point at which it can no longer produce ATP Underlying causes of muscle fatigue are unclear

49. Central Fatigue Occurs when CNS no longer adequately activates motor neurons supplying working muscles Often psychologically based Mechanisms involved in central fatigue are poorly understood

50. Outline Other types –Fibers Fast slow Oxidative glycolytic –Smooth, cardiac –Creatine phosphate –Oxidative phosphorulation Aerobic, myoglobin –Glycolysis Anaerobic, lactic acid

51. Major Types of Muscle Fibers Classified based on differences in ATP hydrolysis and synthesis Three major types –Slow-oxidative (type I) fibers –Fast-oxidative (type IIa) fibers –Fast-glycolytic (type IIx) fibers

52. Characteristics of Skeletal Muscle Fibers

53. Control of Motor Movement Three levels of input control motor-neuron output –Input from afferent neurons –Input from primary motor cortex –Input from brain stem

54. Table 8-1 p282

55. Table 8-2 p285

56. Control of Motor Movement Control of motor movement depends on activity in three types of inputs: –input of afferent neurons associated with spinal reflexes –input from the primary motor cortex, concerned with complex, controlled movements –input from the brain stem (multineuronal motor system) involved in posture

57. Basal nuclei Cerebellum Spinal cord level Periphery Cortical level Subcortical level Brain stem level Premotor cortex Primary motor cortex Somatosensory cortex Premotor and supplementary motor areas Primary motor cortex Brain stem Peripheral receptors Other peripheral events, such as visual input Sensory consequences of movement Muscle fibers Movement Motor neurons Afferent neuron terminals CerebellumThalamus Basal nuclei Sensory areas of cortex Brain stem nuclei (including reticular formation and vestibular nuclei) Thalamus 1 2 2a 2c 2b Fig. 8-24, p. 288

58. Muscle Receptors Two types of muscle receptors. Both are activated by muscle stretch, but monitor different types of information. Muscle spindles monitors muscle length. Golgi tendon organs detect changes in tension.

59. Muscle Spindle Spindles consist of collections of specialized muscle fibers known as intrafusal fibers. Lie within spindle-shaped connective tissue capsules parallel to extrafusal fibers. Each spindle has its own private efferent and afferent nerve supply Contain both afferent and efferent nerve fibers. Plays key role in stretch reflex.

60. Capsule Alpha motor neuron axon Gamma motor neuron axon Afferent neuron axons Extrafusal (“ordinary”) muscle fibers Noncontractile central portion of intrafusal fiber Contractile end portions of intrafusal fiber Intrafusal (spindle) muscle fibers Primary (annulospiral)endings of afferent fibers Secondary (flower-spray) endings of afferent fibers Fig. 8-25a, p. 289

61. Golgi tendon organ (b) Golgi tendon organ Bone Skeletal muscle Tendon Afferent fiber Collagen Fig. 8-25b, p. 289

62. Stretch Reflex Primary purpose is to resist tendency for passive stretch of extensor muscles by gravitational forces when person is standing upright Classic example is patellar tendon, or knee-jerk reflex

63. Outline Other muscle types –Smooth muscle –Cardiac muscle

64. Smooth Muscle Found in walls of hollow organs and tubes. Contains actin and myosin but not troponin, and tropomyosin. Does not form myofibrils and not arranged into sarcomeres. Cells usually arranged in sheets.

65. Smooth Muscle Cell has three types of filaments –Thick myosin filaments Longer than those in skeletal muscle –Thin actin filaments Contain tropomyosin but lack troponin –Filaments of intermediate size Do not directly participate in contraction Form part of cytoskeletal framework that supports cell shape

66. Thick filament Thin filament Plasma membrane One relaxed contractile unit extending from side to side (a) Relaxed smooth muscle cell Thin filament (b) Contracted smooth muscle cell One contracted contractile unit Bundle of thick and thin filaments Dense body Thick filament Fig. 8-29, p. 295

67. Myosin light chain Part of cross- bridge energy cycle Permits binding with actin Phosphorylated myosin cross bridge (can bind with actin) Inactive myosin cross bridge Active myosin light chain kinase Inactive myosin light chain kinase Ca2+–calmodulinCalmodulin Fig. 8-30, p. 296 Calcium Activation of Myosin Cross Bridge in Smooth Muscle

68. Types of Smooth Muscle Multiunit Smooth Muscle Self-excitable (does not require nervous stimulation for contraction) Also called visceral smooth muscle Fibers become excited and contract as single unit Cells electrically linked by gap junctions Can also be described as a functional syncytium Contraction is slow and energy- efficient –Well suited for forming walls of distensible, hollow organs Single-unit Smooth Muscle Neurogenic Consists of discrete units that function independently of one another Units must be separately stimulated by nerves to contract Found –In walls of large blood vessels –In large airways to lungs –In muscle of eye that adjusts lens for near or far vision –In iris of eye –At base of hair follicles

69. Contraction Uncovering of cross- bridge binding sites on actin in thin filament Phosphorylation of myosin cross bridges in thick filament Series of biochemical events Physical repositioning of troponin and tropomyosin Rise in cytosolic Ca 2+ (mostly from extracellular fluid) Rise in cytosolic Ca 2+ (entirely from intracellular sarcoplasmic reticulum) Muscle excitation Skeletal muscleSmooth muscle Contraction Binding of actin and myosin at cross bridges P i Fig. 8-31, p. 296 Comparison of the Role of Calcium In Bringing About Contraction in Smooth, Skeletal, and Cardiac Muscle Cardiac muscle

70. Cardiac Muscle Found only in walls of heart Striated Cells are interconnected by gap junctions Fibers are joined in branching network Innervated by autonomic nervous system

71. Cardiac Muscle Fibers Interconnected by intercalated discs and form functional syncytia Within intercalated discs – two kinds of membrane junctions –Desmosomes –Gap junctions Ap’s

73. Ionic mechanisms of cardiac AP Rp is -85 to -95 MV in atrial fibers; -90-100 mv in purkinje fibers Ap controlled by –Fast Na /Slow Ca channels –Channels stay open longer - creates plateau –Prolonged depolarizarion –Refractory period

74. Excitation contraction coupling Ca sources: –T tubules connected to Sarcoplasmic membrane –ECF Ca influences contraction –Larger T tubules hold more Ca Neg. charged molecules sequester Ca

75. Cell types coordinate function Fast response cells Atria and ventricles Rp -80 to -90mv Do not spontaneously depolarize Short refractory period Fast conduction velocity Slow response cells Conductive system Rp -55 to -60 mV spontaneously depolarize Long refractory period Slow conduction velocity

77. Banding

78. Calcium Release 1

79. Calcium Release 2

80. Crossbridge Interaction

81. Alpha motor neuron axon Gamma motor neuron axon Secondary (flower-spray) endings of afferent fibers Extrafusal (“ordinary”) muscle fibers Capsule Intrafusal (spindle) muscle fibers Contractile end portions of intrafusal fiber Noncontractile central portion of intrafusal fiber Primary (annulospiral) endings of afferent fibers Fig. 8-24, p. 283

82. Smooth Muscle Two major types –Multiunit smooth muscle –Single-unit smooth muscle

83. Multiunit Smooth Muscle Neurogenic Consists of discrete units that function independently of one another Units must be separately stimulated by nerves to contract Found –In walls of large blood vessels –In large airways to lungs –In muscle of eye that adjusts lens for near or far vision –In iris of eye –At base of hair follicles

84. Single-unit Smooth Muscle Self-excitable (does not require nervous stimulation for contraction) Also called visceral smooth muscle Fibers become excited and contract as single unit Cells electrically linked by gap junctions Can also be described as a functional syncytium Contraction is slow and energy-efficient –Well suited for forming walls of distensible, hollow organs