Skeletal Muscle Physiology Basics


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Skeletal Muscle Physiology Basics

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  • Figure 8.9: Cross-bridge activity.
    (a) During each cross-bridge cycle, the cross bridge binds with an actin molecule, bends to pull the thin filament inward during the power stroke, then detaches and returns to its resting conformation, ready to repeat the cycle. (b) The power strokes of all cross bridges extending from a thick filament are directed toward the center of the thick filament. (c) Each thick filament is surrounded on each end by six thin filaments, all of which are pulled inward simultaneously through cross-bridge cycling during muscle contraction.
  • Figure 8.17: Length–tension relationship.
    Maximal tetanic contraction can be achieved when a muscle fiber is at its optimal length (lo) before the onset of contraction, because this is the point of optimal overlap of thick-filament cross bridges and thin-filament cross-bridge binding sites (point A). The percentage of maximal tetanic contraction that can be achieved decreases when the muscle fiber is longer or shorter than lo before contraction. When it is longer, fewer thin-filament binding sites are accessible for binding with thick-filament cross bridges, because the thin filaments are pulled out from between the thick filaments (points B and C). When the fiber is shorter, fewer thin-filament binding sites are exposed to thick-filament cross bridges because the thin filaments overlap (point D). Also, further shortening and tension development are impeded as the thick filaments become forced against the Z lines (point D). In the body, the resting muscle length is at lo. Furthermore, because of restrictions imposed by skeletal attachments, muscles cannot vary beyond 30% of their lo in either direction (the range screened in light green). At the outer limits of this range, muscles still can achieve about 50% of their maximal tetanic contraction.
  • Skeletal Muscle Physiology Basics

    1. 1. SKELETAL MUSCLE Dr Ahmad Saleem
    2. 2. Skeletal Muscle Fibre • 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 – Functional Unit of Skeletal Muscle – Length varies from few mm to many cm. – Diameter of 10 to 100 micron – Multinucleated – Large, elongated, and cylindrically shaped – Fibers usually extend entire length of muscle – Like other cells , MF contains motochondria, microsomes and endoplasmic reticulum etc
    3. 3. • Each Muscle Fiber is surrounded by a plasma membrane called SARCOLEMMA. • Individual MF is enveloped by layer of connective tissue called ENDOMYSIUM ( which lies outside Sarcolemma) • Several MF are enveloped together by another connective tissue called PERIMYSIUM • The entire Muscle is covered all round by EPIMYSIUM. ( Sarcolemma—Endomysium– Perimysium– Epimysium)
    4. 4. • Actin forms the major part of thin filaments. – The thin filaments give rise to I- bands – Actin occurs in two forms • G-Actin ( Globular monomer) – Each molecule contains one molecule of ATP – Molecular weight of about 43000. • F-Actin ( Globular monomer) – Fibrous, thickness of 6-7 nm, polymerized G-Actin, contains ADP. – Polymerization occurs in presence of Calcium or Magnesium ions.
    5. 5. • Myosin –II – Found in Thick Filaments – Mol Weight of about 460,000. – Chief Actin Binding Constituent. – Hexamer containing two identical heavy chains and 4 light chains.
    6. 6. • Troponin – Troponin –C – Can bind an release Calcium Ions. – Troponin-I – Exerts an inhibitory action over Actin-Myocin interaction when Troponin C is without Calcium. – Troponin T – Serves to bind Troponin C and Troponin I subunits with Tropomyosin-Actin Complex. (Troponin complex is found only in Striated Muscle)
    7. 7. Muscle Tendon Muscle fiber (a single muscle cell) Connective tissue Fig. 8-2, p. 255
    8. 8. 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 – Light bands , Only Actin, Isotropic to polarized light-thus I-Bands. – Dark bands, Mainly myosin, Anisotropic to polarized light-Thus A-Bands
    9. 9. Muscle fiber Dark A band Light I band Myofibril Fig. 8-2, p. 255 A T-tubule (or transverse tubule) is a deep invagination of the sarcolemma, which is the plasma membrane, only found in skeletal and cardiac muscle cells. These invaginations allow depolarization of the membrane to quickly penetrate to the interior of the cell.
    10. 10. Figure 1.3
    11. 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. 12. Z line A band I band Portion of myofibril M line Sarcomere H zone Thick filament Thin filament Cross bridges M line H zone Z line A band I band Thick filament Thin filament Myosin Actin Fig. 8-2, p. 255
    13. 13. I band A band I band Cross bridge Thick filament Thin filament Fig. 8-4, p. 256
    14. 14. Myosin • Component of thick filament • Composed of SIX polypeptide chains, two identical heavy chains, and four light chains. • The two heavy chains wrap spirally around each other for form a double helix; however one end of each of these chains is folded into a globular protein mass called the head; the elongated portion is called the tail. • 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. 15. Cross Bridges in Myosin Filaments •The protruding arms and heads together are called cross-bridges. •Each cross-bridge is believed to be flexible at two points called hinges. •One where the arm leaves the body of the myosin fiilament. •Where the two heads attach to the arm. ATPase activity of Myosin Head Another feature of myosin head, essential for muscle contraction is that it functions as an ATPase enzyme. This property allows the head to cleave ATP and to use the energy to energize the contraction.
    16. 16. Structure and Arrangement of Myosin Molecules Within Thick Filament
    17. 17. 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
    18. 18. The Actin Filament • The back bone of the actin filament is a double- stranded F-Actin protein molecule. • Each strand of double F-actin helix is composed of polymerized G-actin molecules. • Attached to each one of the G-actin molecules is one molecule of ADP. It is believed that these ADP molecules are the active sites on the actin filaments with which the cross-bridges of the myosin filaments interact to cause muscle contraction.
    19. 19. Composition of a Thin Filament
    20. 20. • A pure actin filament without the presence of troponin-tropomyosin complex binds strongly with myosin molecules, in the presence of Magnesium and ATP. • However if the troponin-tropomyosin complex is added to the actin filament, this binding does not take place. • Thus the active sites on the normal actin filament of relaxed muscle are inhibited or actually physically covered by the troponin- tropomyosin complex. • For contraction to take place the inhibitory effect of the T-T complex must itself be inhibbitted.
    21. 21. 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.
    22. 22. Large amount of Calcium Ion • In the presence of large amounts of calcium ions the inhibitory effect of T-T complex is inhibited. • Calcium ion combines with troponin-C, the Troponin complex undergoes conformational change that moves it deeper into the groove between the two actin strands. • This uncovers the active sites of the actin , thus allowing the contraction to proceed.
    23. 23. 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 Ca2+
    24. 24. Role of Calcium in Cross-Bridge Formation
    25. 25. Cross-bridge interaction between actin and myosin brings about muscle contraction by means of the “Sliding Filament Mechanism.” Walk-Along Theory of Contraction
    26. 26. 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
    27. 27. Sliding Filament Mechanism • Increase in Ca2+ starts filament sliding • Decrease in Ca2+ 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
    28. 28. Figure 1.5
    29. 29. Fig. 8-9, p. 260 Basic 4 steps
    30. 30. Power Stroke • Activated cross bridge bends toward center of thick filament, “rowing” in thin filament to which it is attached • Sarcoplasmic reticulum releases Ca2+ 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
    31. 31. Power Stroke • Hydrolysis of ATP transfers energy to myosin head and reorients it • Contraction continues if ATP is available and Ca2+ level in sarcoplasm is high
    32. 32. 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
    33. 33. Changes in Banding Pattern During Shortening
    34. 34. Relaxation • Depends on reuptake of Ca2+ into sarcoplasmic reticulum (SR) • Acetylcholinesterase breaks down ACh at neuromuscular junction • Muscle fiber action potential stops • When local action potential is no longer present, Ca2+ moves back into sarcoplasmic reticulum
    35. 35. Rigor Mortis • Rigidity caused by loss of all the ATP which is required to cause the separation of the cross- bridges from the actin filament during the relaxation process. • Thus, several hours after death the muscles of the body go into a state of contracture, called “ Rigor Mortis”, i.e. the muscle contracts and becomes rigid even without action potential. • The muscle remains in rigor until the muscle proteins are destroyed by autolysis
    36. 36. Terminal button Acetylcholine- gated cation channel Acetylcholine T tubule Surface membrane of muscle cell Lateral sacs of sarcoplasmic reticulum Tropomyosin Troponin Cross-bridge binding Myosin cross bridge Actin Fig. 8-12, p. 262
    37. 37. T Tubules and Sarcoplasmic Reticulum
    38. 38. 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)
    39. 39. 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 Ca2+ from sarcoplasmic reticulum into cytosol
    40. 40. Relationship Between T Tubule and Adjacent Lateral Sacs of Sarcoplasmic Reticulum
    41. 41. Outline • Mechanics – Tendons – Twitch – Motor unit – Motor unit recruitment – Fatigue – Asynchronous recruitment – Twitch, tetanus, summation – Muscle length, isometric, isotonic • Tension, origin, insertion
    42. 42. 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
    43. 43. 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
    44. 44. 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
    45. 45. 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
    46. 46. Schematic Representation of Motor Units in Skeletal Muscle
    47. 47. 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
    48. 48. Summation and Tetanus
    49. 49. 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
    50. 50. Fig. 8-17, p. 268
    51. 51. 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
    52. 52. 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 Ca2+ back into sarcoplasmic reticulum during relaxation depends on energy derived from breakdown of ATP
    53. 53. 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 O2 is present • Glycolysis – Supports anaerobic or high-intensity exercise
    54. 54. 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
    55. 55. 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
    56. 56. Outline • Other types – Fibers • Fast • slow • Oxidative • glycolytic – Smooth, cardiac – Creatine phosphate – Oxidative phosphorulation • Aerobic, myoglobin – Glycolysis • Anaerobic, lactic acid
    57. 57. 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
    58. 58. Characteristics of Skeletal Muscle Fibers
    59. 59. 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
    60. 60. Muscle Spindle Structure • 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 – Play key role in stretch reflex
    61. 61. Muscle Spindle Function
    62. 62. 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
    63. 63. 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
    64. 64. Patellar Tendon Reflex
    65. 65. Outline • Other muscle types – Smooth, cardiac – This information is covered in detail in the lecture on the heart.
    66. 66. Smooth Muscle • Found in walls of hollow organs and tubes • No striations – Filaments do not form myofibrils – Not arranged in sarcomere pattern found in skeletal muscle • Spindle-shaped cells with single nucleus • Cells usually arranged in sheets within muscle • Have dense bodies containing same protein found in Z lines
    67. 67. 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
    68. 68. Intermediate filament Thick filament Thin filament Dense body Fig. 8-28, p. 288 Stepped art
    69. 69. Calcium Activation of Myosin Cross Bridge in Smooth Muscle
    70. 70. Comparison of Role of Calcium In Bringing About Contraction in Smooth Muscle and Skeletal Muscle
    71. 71. Smooth Muscle • Two major types – Multiunit smooth muscle – Single-unit smooth muscle
    72. 72. 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
    73. 73. 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
    74. 74. 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