4. Muscle Physiology detail notes and power point

A detail information about muscle physiology

1. MUSCLE PHYSIOLOGY Arba Minch University CMHS School of Medicine Department of Biomedical Science Physiology Unit Muscle Physiology By: Zelalem K. (BSc, MSc in Medical Physiology)

2. Objectives At the end of this chapter the student will be able to List the 3 types of muscle Define characteristics of muscle Enumerate functions of muscle Compare skeletal, smooth & cardiac muscle 2 11/12/2023 The Physiology of Muscles

3. Introduction Muscle is one of our 4 tissue types and combined with nerves, blood vessels , and various connective tissues . 3 11/12/2023 The Physiology of Muscles Introduction Part I The Physiology of Muscles

4. Functions of muscle 1 . Produces movement of Body parts Blood through the blood vessels Lymph through the lymphatic vessels Food through the GI tract Bile out of the gallbladder and into the digestive tract Urine through the urinary tract Semen through the male and female reproductive tracts A newborn through the birth canal 4 11/12/2023 The Physiology of Muscles Introduction Part I The Physiology of Muscles

5. 2 . Maintenance of posture Muscle contraction is constantly allowing us to remain upright . Muscles of your neck are keeping your head up right now. As you stand, your leg muscles keep you on two feet. 3 . Thermogenesis Generation of heat, occurs via shivering, a n involuntary contraction of skeletal muscle. 5 11/12/2023 The Physiology of Muscles Introduction Part I The Physiology of Muscles

6. 4 . Stabilization of joints Muscles keep the tendons that cross the joint. This does a wonderful job of maintaining the integrity of the joint. 6 11/12/2023 The Physiology of Muscles Introduction Part I The Physiology of Muscles

7. 11/12/2023 7 The Physiology of Muscles Introduction Classification of muscles Part I The Physiology of Muscles

8. 11/12/2023 8 Skeletal muscle Voluntary muscle tissue Have cross striations (interdigitating thick and thin filaments). Cells are long and multinucleated Contract only in response to stimuli (no syncytial bridges between cells). The Physiology of Muscles Introduction Part I The Physiology of Muscles

9. 11/12/2023 9 Cardiac muscle i . Involuntary muscle tissue ii. Have cross striation iii. Cells are branched and mononucleated iv. Have intercalated disc with gap junctions Smooth Muscle Involuntary muscle tissue Alternating dark and light bands are absent. Uninucleated ; contain 1 centrally placed nucleus The Physiology of Muscles Introduction Part I The Physiology of Muscles

10. Physiological Classification 1. Voluntary muscle Skeletal muscle (CNS, somatic motor neurons). 2. Involuntary muscle Cardiac muscle (Intrinsic + Extrinsic factors, ANS + Hormonal) Smooth muscle (Intrinsic + Extrinsic factors, ANS + Hormonal) The Physiology of Muscles Introduction Part I 11/12/2023 The Physiology of Muscles 10

11. Characteristics of Muscle Tissue 1 . Excitability The ability to receive & respond to a stimulus . 2 . Contractility The ability to shorten forcibly when adequately stimulated. This is the defining property of muscle tissue. 3 . Extensibility The ability to be stretched. 4 . Elasticity The ability to recoil & resume original length after being stretched or contracted. 11 11/12/2023 The Physiology of Muscles Introduction Part I The Physiology of Muscles

12. Skeletal muscle Voluntary muscle tissue Contain nervous and connective tissues . Surrounded by dense irregular connective tissue known as the epimysium Perimysium surrounds several bundles known as muscle fascicles Each muscle fiber is surrounded by a fine layer of loose connective tissue, the endomysium . 12 11/12/2023 The Physiology of Muscles Skeletal Muscles Part I The Physiology of Muscles

13. 13 The Physiology of Muscles Skeletal Muscles Skeletal Muscle Microanatomy S keletal muscle cell is a skeletal muscle fiber . Diameter = 100 µm length = 30 cm 11/12/2023 Part I The Physiology of Muscles Whole muscle→ Muscle fascicle → Muscle fiber → Myofibrils → Myofilament → Sarcomere

14. The Sarcolemma Thin membrane enclosing a skeletal muscle fiber Consists of a true cell membrane, called the plasma membrane The Physiology of Muscles Skeletal Muscles Part I 11/12/2023 The Physiology of Muscles 14

15. Sarcoplasm Is cytoplasm of myofibril Is the ICF fluid between myofibrils Containing large quantities of K + , Mg 2+ , and PO 4 -, plus multiple protein enzymes. High numbers of mitochondria that lie parallel to the myofibrils (ATP) . The Physiology of Muscles Skeletal Muscles Part I 11/12/2023 The Physiology of Muscles 15

16. 11/12/2023 16 Sarcoplasmic reticulum (SR) a. Smooth ER of muscle fiber b. It is an internal tubular structure that runs between the myofibrils. c. It is closed at both ends. d. It is not continuous with the sarcolemma. e. Functions : i . Stores Ca 2+ in the terminal cisternae ii. Uptake and release of Ca 2+ Calsequestrin is sarcoplasmic protein that binds Ca 2+ . The Physiology of Muscles Skeletal Muscles Part I The Physiology of Muscles

17. Transverse tubule (T-tube) a. It is an invagination of the surface of the muscle membrane. b. It is found at the junction of A and I-band. c. One end of the tube is open to the extracellular space, but its other end is closed. d. Function: rapid transmission of the AP from the cell membrane to all the fibers on the muscle. Each T-tubule is flanked by a terminal cisterna this forms a so called triad consisting of 2 terminal cisternae & 1 T-tubule branch. 17 11/12/2023 The Physiology of Muscles Skeletal Muscles Part I The Physiology of Muscles

18. Myofibrils Are composed of actin and myosin filaments Each muscle fiber contains several thousand myofibrils Each myofibril composed of 1500 myosin and 3000 actin. Protein responsible for muscle contraction. The Physiology of Muscles Skeletal Muscles Part I 11/12/2023 The Physiology of Muscles 18

19. Myofilaments The thick filaments → myosin Th e thin filaments → actin The myosin and actin filaments interdigitate and cause the myofibrils to have alternate light and dark bands. 11/12/2023 19 The Physiology of Muscles Skeletal Muscles Part I The Physiology of Muscles

20. Thick Filament a. It is called myosin (an actin -binding protein). b. Composition 2 heavy chains 4 light chains 2 heads → Myosin head (cross-bridge) → Actin- binding site → ATP-binding site (ATP ase ) → Hydrolyzes ATP 1 long tail → form core of the thick filament 1 thick filament has 300 myosin heads. 1 cross-bridge has 2 identical heads The Physiology of Muscles Skeletal Muscles Part I 11/12/2023 The Physiology of Muscles 20 Actin-binding site ATP-binding site

21. 11/12/2023 21 Thin filaments a. They are called actins. b. Components Globular proteins Actin Globular -Actin (G-actin) Fibrillar- Actin (F-actin, a polymer of G-actins) ii. Troponin 2. Non-Globular proteins tropomyosin The Physiology of Muscles Skeletal Muscles Part I The Physiology of Muscles

22. Regulatory proteins A. Tropomyosin a. A rod-shaped molecule stretched along actin. b. 1 tropomyosin molecule covers 7 actin monomers. c. It blocks the binding sites of myosin. B. Troponins a. Troponin T: it binds other troponins to tropomyosin. b. Troponin I: inhibits the interaction of myosin with actin c. Troponin C: binds Ca 2+ that initiates contraction The Physiology of Muscles Skeletal Muscles Part I 11/12/2023 The Physiology of Muscles 22

23. Titin Filamentous protein MW = 3 million, the largest protein It is very springy Function Holds the myosin and actin filaments in place Tethers myosin to z lines, Serves as a scaffold for sarcomere . Prevents overstretching of sarcomere ?cell signaling? Stretch sensor 11/12/2023 23 The Physiology of Muscles Skeletal Muscles Part I The Physiology of Muscles

24. Sarcomeres Each myofibril is made up 1000’s of repeating individual units known as sarcomeres (lies between two successive Z disks) Each sarcomere is an ordered arrangement of thick & thin filaments. Notice that it has regions of: Thin filaments (pinkish fibers) Thick filaments (purple fibers) Regions of thick & thin filaments overlapping. 11/12/2023 24 The Physiology of Muscles Skeletal Muscles Part I The Physiology of Muscles

25. Molecular geometry Differences in Refractive indices viewed under polarized light. A-Band a. The darker area in the center of the sarcomere. b. It is due to the orderly arrangement of thick filaments. c. Thin filaments may extend into the A-band. H-Band a. It contains only myosin tails (no myosin heads) b. There are no thin filaments. c. When the muscle is relaxed The Physiology of Muscles Skeletal Muscles Part I 11/12/2023 The Physiology of Muscles 25

26. M-line Site of the reversal polarity of the myosin molecules in each of the thick filaments. It vertically bisects the H-Band It contains 2 important proteins: Myomesin: a structural protein that links neighboring thick filaments Creatinine phosphokinase: an enzyme that maintains adequate ATP conc. in working muscle fibers. The Physiology of Muscles Skeletal Muscles Part I 11/12/2023 The Physiology of Muscles 26

27. I-Band The lighter area on either side of the z-lines. Each sarcomere contain half of the two I-bands. c. Thin filaments Z-Line/Disc a. Dense line in the center of each light band. b. Separates one sarcomere from the next. c. It is the attachment site for the thin filaments. The Physiology of Muscles Skeletal Muscles Part I 11/12/2023 The Physiology of Muscles 27

28. Muscle Contraction Sliding-Filament Model ( Hanson & Huxley , 1955) This model theorizes that sliding in of the filaments (thick & thin) toward the center of muscle and sarcomere is responsible for the shortening and force of contraction. Also called the “walk-Along” theory of contraction 11/12/2023 28 The Physiology of Muscles Skeletal Muscles; Contraction Part I The Physiology of Muscles

29. Muscle Contraction… Resting state: Troponin I and tropomyosin covers the sites where myosin heads bind to actin. (At rest: interaction of thick and thin filaments is inhibited) . Troponin-tropomyosin complex is called “Relaxing-Protein” because it inhibits the interaction between myosin and actin. 11/12/2023 29 The Physiology of Muscles Skeletal Muscles; Contraction Part I The Physiology of Muscles

30. b. Contractile state The invading AP to T-tubule Ca 2+ released from SR Ca 2+ Binds to troponin C Binding of troponin I to actin is weakened Tropomyosin moves laterally uncovers binding sites for myosin heads Contraction ( in the presence of ATP ) 11/12/2023 30 The Physiology of Muscles Skeletal Muscles; Contraction Part I The Physiology of Muscles

31. ATP as the energy source for contraction When a muscle contracts, work is performed, and energy is required. a. actin + myosin + ATP + Ca 2+ → CONRACTION b. Actin + myosin + ATP - Ca 2+ → RELAXATION c. ATP is needed for relaxation d. In the absence of Ca 2+ ATP is not hydrolyzed e. 3 ATP molecules are needed for 1 contraction & relaxation cycle For the formation of the actin-myosin complex For the removal of myosin head from actin To pump out Ca 2+ from the sarcoplasm to sequester it into the SR (Ca 2+ - Mg 2+ pump/ SERCA ) 11/12/2023 31 The Physiology of Muscles Skeletal Muscles; Contraction Part I The Physiology of Muscles

32. Sources of energy for muscle contraction The energy source of contraction is ATP The ATP is split to form ADP + Pi The ADP is rephosphorylated to form new ATP There are 3 sources of the energy for rephosphorylation ADP 1. Phosphocreatine : carries a high-energy phosphate bond 2.“Glycolysis” of glycogen previously stored in the muscle cells 3. Oxidative metabolism: combining O 2 with various other cellular foodstuffs to liberate ATP. 11/12/2023 32 The Physiology of Muscles Skeletal Muscles; Contraction Part I The Physiology of Muscles

33. Types of Muscle Contraction Isometric Contractions Muscle does not shorten during contraction An example is carrying an object in front of you. The weight of object would be pulling down word Your hands would be opposing the motion with equal force going upward Your biceps isometrically contracting The Physiology of Muscles Skeletal Muscles; Contraction Part I 11/12/2023 The Physiology of Muscles 33

34. Isotonic Contractions Shorten muscle at a constant tension Muscle shorten but the tension on the muscle remains constant The muscle shortens against a fixed load The Physiology of Muscles Skeletal Muscles; Contraction Part I 11/12/2023 The Physiology of Muscles 34

35. 11/12/2023 35 The Physiology of Muscles Skeletal Muscles: Motor Unit The Motor Unit A motor neuron and the muscle fibers it innervates. Part I The Physiology of Muscles

36. Excitation-Contraction Coupling/ Electromechanical Coupling Def. ~ is the process of linking AP (electrical signal) to muscle contraction Electrical events precedes mechanical events We can divide the whole process into 4 -steps Excitation Excitation-Contraction Coupling Contraction Relaxation 36 11/12/2023 The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles

37. Excitation All cells have a voltage difference across their plasma membrane This charge separation is known as a E m . This charge separation at rest is known as a RMP The value for RMP in inactive muscle cells is – 90 mv . RMP can be changed by influx or efflux of charge. 37 11/12/2023 The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles

38. Excitation… Within the muscle, each axon branch into multiple small extensions called telodendria . Each telodendrium ends in synaptic end bulb. Synaptic end bulb is filled with vesicles, contain NT, Ach . Minute space between the synaptic end bulb & the sarcolemma is synaptic cleft . There is a depression in the sarcolemma at the synaptic cleft known as the motor end plate Motor end plate is chock full of Ach receptors . 38 11/12/2023 The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles

39. 11/12/2023 The Physiology of Muscles 39 Axon collateral of somatic motor neuron Sarcolemma Synaptic end bulbs Motor end plate The Physiology of Muscles Skeletal Muscles: ECC Part I Voltage-gated Ca 2+ channel Motor endplate

40. Mechanism of Excitation A nerve signal arrive at the synaptic end bulb and cause the ACh -containing vesicles to undergo exocytosis . ACh will diffuse across the synaptic cleft & bind to the ACh receptors. These receptors are ligand-gated Na + channels . The binding of ACh causes them to open. Na + rush into the cell, making the local cell interior more positive = depolarization = It is a local event! 40 11/12/2023 The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles

41. Mechanism of Excitation… Adjacent to the motor end plate, the sarcolemma contains voltage-gated ion channels . For these channels to open, the E m must depolarize from its resting value of –90 mV to –50 mV (threshold). The degree of depolarization depends on How much Na + influx occurred Which in turn depends on how many Na + channels were opened by binding ACh. 41 11/12/2023 The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles

42. Mechanism of Excitation… If the E m fails to depolarize to threshold , nothing will happen. The E m will soon return to normal and = no muscle contraction If the E m does reach threshold, 2 -types of voltage-gated ion channels will open sequentially: Fast Na + channels, slow K + channels If E m reaches threshold, fast Na + channels open and Na + rushes in causing the E m to depolarize to +30 mV. The depolarization stops when the Na + channels become inactivated. 42 11/12/2023 The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles

43. Mechanism… At this point, slow K + channels have opened & K + efflux occurs. This returns E m back to its resting level. This is repolarization . 43 11/12/2023 The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles

44. Mechanism of Excitation… AP can propagate itself across the surface of the plasma membrane. The depolarization caused by the Na + influx in one area of the sarcolemma causes voltage-gated channels in the adjacent membrane to open. The resulting ionic influx then causes voltage-gated channels to open in the next patch of membrane and so on and so on . 44 11/12/2023 The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles

45. Excitation-Contraction Coupling AP travels along the sarcolemma going in both directions away from the motor end plate. T-tubules spread the AP T-tubular sarcolemma contains voltage sensitive proteins that change their conformation in response to a significant  E m . 45 11/12/2023 The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles voltage sensitive proteins

46. These are physically linked to Ca 2+ channels in the SR membrane Upon  E m , the voltage sensors change their conformation. This mechanically opens the Ca 2+ channels in the SR. A large amount of Ca 2+ enters the sarcoplasm . Ca 2+ interacts with troponin C. The 2 contractile proteins slide one over the other. The sarcomere shorten (muscle contraction). 46 11/12/2023 The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles

47. 11/12/2023 47 Discharge of motor neuron ↓ Release of Ach at motor endplate ↓ Binding of Ach to n AchR ↓ gNa + and gK + in endplate membrane ↓ Generation of EPP →MEPP ↓ Generation of AP in muscle fibers ↓ Inward spread of depolarization along T-tubules ↓ Release of Ca 2+ from SR and diffusion to thick and thin filaments ↓ Binding of Ca 2+ to troponin C, uncovering myosin-binding sites on actin ↓ Formation of cross-linkages b/n actin and myosin and sliding of thin on thick filaments, producing movement The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles Contraction

48. 48 11/12/2023 The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles

49. 11/12/2023 49 Relaxation of Muscle.   Removal of Ca 2+ from the myoplasm into the SR. b. For Ca 2+ removal from the sarcoplasm the third ATP is consumed by Ca 2+ -Mg 2+ -ATPase/ SERCA After removal of Ca 2+ : i . Troponin returns to its original conformational state. ii. Tropomyosin inhibition of Myosin-Actin interaction is restored. iii. Cross-bridge cycling stops and the muscle is returned to its resting state. d. Breakdown of Ach by AChE. The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles

50. Changes Banding H-zone: Disappears Z-line: Gets considerably darker I-band: Narrower/smaller A-band: κ Contractile proteins: no change in myosin or actin c. Sarcomere: Shortens The Physiology of Muscles Skeletal Muscles: ECC Part I 11/12/2023 The Physiology of Muscles 50

51. 11/12/2023 51 Ion channels involved: Voltage-gated Ca 2+ channels ( α -motor neuron) Ligand-gated Na + channels (motor endplate) Voltage-gated Na + channel (contiguous to the motor endplate) Voltage-gated K + channel (contiguous to the motor endplate) Mechanical gated Ca 2+ Channel (SR membrane) The Physiology of Muscles Skeletal Muscles: ECC Part I The Physiology of Muscles

52. Muscle Fatigue Temporary inability of (muscle/nerve cell) to respond to a stimulus after continuous stimulation. Results primarily from a relative deficit of ATP. Depletion of muscle glycogen. Depletion neuromuscular transmission at NMJ The Physiology of Muscles Skeletal Muscle Part I 11/12/2023 The Physiology of Muscles 52

53. Rigor Mortis It is a state of muscle contracture, i.e., contraction produced without AP and not followed by relaxation. It is a contracture which occurs in the muscles after death. It starts in small muscles (2-3hrs) after death and involves all muscles in 12 hrs. The rigidity is due to depletion of ATP from the muscle. Ca 2+ diffuses out of the SR & can not be recollected by the SERCA. Ca 2+ initiates muscle contraction using the remaining ATP molecules, relaxation does not occur because calcium is not recollected back into the SR, and no ATP is available to disconnect the myosin heads from actin. The Physiology of Muscles Skeletal Muscles: Clinical correlates Part I 11/12/2023 The Physiology of Muscles 53

54. g. It disappears when muscle fibers are autolysed by lysosomal enzymes released after death. h. It starts to disappear 14hrs after death and completed in 24hrs. i . High environmental T o accelerates the appearance and disappearance of rigor mortis. j. The extent of rigor mortis is used medically to determine the time of death. The Physiology of Muscles Skeletal Muscles: Clinical correlates Part I 11/12/2023 The Physiology of Muscles 54

55. 11/12/2023 55 Neuromuscular Transmission 1. Def. ~ a synaptic transmission between an  -motor neuron and skeletal muscle fiber. 2. Physiologic anatomy Presynaptic end bulb Synaptic vesicles Diameter Φ = 50nm Membrane bounded Contains Ach transporter and Ca 2+ binding proteins iv. NT: Ach The Physiology of Synaptic Transmission The Neuromuscular transmission The Neuromuscular Junction Part I The Physiology of Muscles

56. 56 The Physiology of Synaptic Transmission The Neuromuscular transmission 11/12/2023 Structure of a neuromuscular junction. Part I The Physiology of Muscles

57. 11/12/2023 57 b. Synaptic cleft Contents Connective tissue, basal lamina Acetylcholine esterase ( AchE ) c. Postsynaptic membrane Acetylcholine receptors Nicotinic receptors Legend gated sodium channels The Physiology of Synaptic Transmission The Neuromuscular Transmission Part I The Physiology of Muscles

58. 11/12/2023 58 3. Acetylcholine 1. Synthesis Site: nerve terminals (presynaptic neuron). Sources: acetyl CoA (from the mitochondria) choline (taken up from ECF) Enzyme: choline acetyltransferase Choline + Acetyl CoA Choline - o- acetyltransferase Ach 2. Storage: Synaptic vesicles The Physiology of Synaptic Transmission The Neuromuscular transmission Part I The Physiology of Muscles

59. 11/12/2023 59 The Physiology of Synaptic Transmission The Neuromuscular transmission Why in a vesicle??? Concentration Protection from degradation Allows for regulation… Part I The Physiology of Muscles

60. 11/12/2023 60 3. Release: → exocytosis Vesicle formation → filling with NT → associated with cytoskeletal elements → docking at the presynaptic membrane → membrane fusion → exocytosis at active zone . Proteins involved in NT release Synaptobrevin Syntaxin The Physiology of Synaptic Transmission The Neuromuscular transmission Part I The Physiology of Muscles

61. 11/12/2023 61 The Physiology of Synaptic Transmission The Neuromuscular transmission The synaptic vesicle cycle Part I The Physiology of Muscles

62. 11/12/2023 62 c. Transmitter release is controlled by Ca 2+ influx Ca 2+ influx → binds to Synaptobrevin → Synaptobrevin - binds to Syntaxin → vesicle membrane fusion → Ach release ii. Fates of Ca 2+ Intracellular sequestration Ca 2+ -Na + antiport The Physiology of Synaptic Transmission The Neuromuscular transmission Part I The Physiology of Muscles

63. 11/12/2023 63 4. Acetylcholine receptors b. Types: i . Nicotinic : NMJ + Autonomic ganglia + CNS Blocked by curare ii. Muscarinic : PNS (Vagus n, heart muscle smooth muscle of intestine, CNS) Blocked by atropine The Physiology of Synaptic Transmission The Neuromuscular transmission Part I The Physiology of Muscles

64. 11/12/2023 64 d. Actions 2α subunits occupied → conformational change → opening of the gate → permeability to Na + , K + . Na + enters, K + leaves the cell → cell depolarizes→ EPP → MEP → AP. The Physiology of Synaptic Transmission The Neuromuscular transmission Part I The Physiology of Muscles

65. 11/12/2023 65 The fate of ACh  Enzymatic inactivation ( AchE ) Re-uptake (by nerve terminal, basal lamina) It diffuses out of the synaptic cleft… The Physiology of Synaptic Transmission The Neuromuscular transmission Part I The Physiology of Muscles

66. 11/12/2023 66 NB. Only one motor neuron innervates a skeletal muscle fiber. Only excitatory input is received by muscle fiber ( No inhibitory input ). Only one NT, Ach, activates the muscle fibers. Only one kind of receptor, n AchR , mediates the actions of Ach. The Physiology of Synaptic Transmission The Neuromuscular transmission Part I The Physiology of Muscles

67. 67 The Physiology of Synaptic Transmission The Neuromuscular transmission 11/12/2023 Events at the neuromuscular junction… Part I Summery The Physiology of Muscles

68. Myasthenia Gravis (extreme muscle weakness) Autoimmune disease where antibodies attack the ACh receptors on NMJs. Results in progressive weakening of the skeletal muscles . Treated with anticholinesterases such as neostigmine or physostigmine . These decrease the activity of acteylcholinesterase (ACE) . 11/12/2023 68 My =muscle, Asthen =weakness, Gravi =heavy The Physiology of Muscles Skeletal Muscles: Clinical correlates Part I The Physiology of Muscles

69. Eaton Lambert Myasthenic Syndrome Autoimmune antibodies attack calcium channals in presynaptic membrane Not respond to AchE inhibitors D- tubo curarine Poison to catch a fish Toxin loaded with arrow Binds with nicotinic receptors at NMJ Hemicholiniam Vesamicole Botulinum Toxin Suceinylcholine 11/12/2023 69 The Physiology of Muscles Skeletal Muscles: Clinical correlates Part I The Physiology of Muscles

70. Smooth Muscle Involuntary muscle tissue Smaller uninucleated cells Lack any visible striations. 70 11/12/2023 The Physiology of Muscles Smooth Muscles Part II The Physiology of Muscles

71. Smooth Muscle… Lack T-tubules but propagation of AP is analog caveolae . Have a scanty SR Innervated by the ANS unlike skeletal muscle which is innervated by the SNS (over which you have control). Only the endomysium is present. No perimysium or epimysium. No Z discs , instead thin filaments are attached to protein structures dense bodies which attach to the sarcolemma. Tropomyosin is present but not blocking actin’s myosin binding sites Troponin is not present 11/12/2023 71 The Physiology of Muscles Smooth Muscles Part II The Physiology of Muscles

72. 11/12/2023 Physical structure of smooth muscle 72 The Physiology of Muscles Smooth Muscles Part II The Physiology of Muscles

73. Smooth muscle location 1. Cardiovascular system Smooth muscle in blood vessels regulates blood flow through vital organs, also helps regulate blood pressure. 2. Digestive systems Rings of smooth muscle ( sphincters ) regulate movement along internal passageways. Smooth muscle lining the passageways alternates contraction & relaxation to propel matter through the alimentary canal . 73 11/12/2023 The Physiology of Muscles Smooth Muscles Part II The Physiology of Muscles

74. 3. Integumentary system Regulates blood flow to the superficial dermis. Allows for piloerection . 4. Respiratory system Alters the diameter of the airways & changes the resistance to airflow. 5. Urinary system Sphincters regulate the passage of urine . 11/12/2023 74 The Physiology of Muscles Smooth Muscles Part II The Physiology of Muscles

75. 6. Reproductive system Females Assists in the movement of the egg ( sperm ) through the female reproductive tract. Plays a large role in childbirth. Males Movement of sperm along the male reproductive tract. Erection and ejaculation. 11/12/2023 75 The Physiology of Muscles Smooth Muscles Part II The Physiology of Muscles

76. Smooth muscle contraction Begins with the opening of membrane channels Ligand-gated (NTs, hormones, metabolites). Voltage-gated, or Mechanically-gated (stretch). Channels will allow significant Ca + entry from the ECF . Ca + binds to regulatory molecule calmodulin & activates it. Activated calmodulin activates an enzyme called Myosin Light Chain Kinase (MLCK) . 76 11/12/2023 The Physiology of Muscles Smooth Muscles Part II The Physiology of Muscles

77. Stimulus Ca 2+ enters the cell through Ca 2+ channels or released from the SR. The Ca 2+ binds to CaM to form Ca 2+ - CaM complex, Which activates MLCK Active MLCK phosphorylates the myosin light chain Leading to attachment of the myosin head with the actin Contraction of the SM. 11/12/2023 77 The Physiology of Muscles Smooth Muscles Part II The Physiology of Muscles

78. Smooth muscle Relaxation Relaxation of SM occurs when Ca 2+ ↓below a critical level as Ca 2+ is pumped out of the cell or into the SR. Ca 2+ is then released from CaM Myosin phosphatase removes phosphate from the myosin light chain Causing detachment of the myosin head from the actin filament and relaxation of the SM 11/12/2023 78 The Physiology of Muscles Smooth Muscles Part II The Physiology of Muscles

79. Types of Smooth Muscle Smooth muscle varies widely from organ to organ in terms of Physical dimensions Fiber arrangement Responsiveness to certain stimuli Characteristics of innervation Function 11/12/2023 79 The Physiology of Muscles Smooth Muscles Part II The Physiology of Muscles

80. Multi-Unit Smooth Muscle No gap junctions: e ach fiber is independent of all the others. Responsible to neural & hormonal controls No pacemaker cells Less common Found in Large airways to the lungs Large arteries Iris Heir roots 11/12/2023 80 The Physiology of Muscles Smooth Muscles Part II The Physiology of Muscles

81. Single Unit Smooth Muscle More common Are large sheets of mononucleated small cells Cells contract as a unit because they are all connected by gap junctions (functional syncytium ) Have unstable RMP Some will contract rhythmically due to pacemaker cells that have a spontaneous rate of depolarization. Found in gut, ureter , small blood vessels and uterus. 11/12/2023 81 The Physiology of Muscles Smooth Muscles Part II The Physiology of Muscles

82. 11/12/2023 82 CARDIAC MUSCLE The physiological basis of heart pumping (contracting of the heart) is to propel blood through the circulatory system. It has SAME contractile machinery with some degree of modification . (Actins, myosin…) c. REGULATION is done by intrinsic and extrinsic factors: neuronal (ANS) + hormonal. d. In the course of an average life span the heart will contract = 72 beats x 60 min x 24hrs x 365d x 70 years = 3x10 9 e. Abundance of connective tissue (prevent muscle rupture, prevent over- stretching during periods of increased venous return). The Physiology of Muscles Cardiac Muscle Part III The Physiology of Muscles

83. 11/12/2023 83 2. Cardiac Muscle Vs. Skeletal Muscle 1. Cardiac Muscle. A cardiac myocyte has a single nucleus Has abundant amount of mitochondria (30%) + myoglobin which makes it fatigue resistant (myoglobin facilitates the transport of oxygen from the sarcolemma to the mitochondria) A cardiac cells are joined end-to-end by intercalated discs i. Attach one cell to the next by means of desmosomes ii. Connect the thin filament of the myofibrils of adjacent cells. ( Mechanical + electrical coupling ) iii. Contain gap junctions which is synchronizing the contractions of heart muscle cells. The Physiology of Muscles Cardiac Muscle Part III The Physiology of Muscles

84. 84 11/12/2023 The Physiology of Muscles Cardiac Muscle Part III The Physiology of Muscles 4. The T-tubule is larger and it is found at z-line 5. The SR - makes contact with T-tubule and the cell membrane.