Dr. Dinesh T,                                   Junior resident.11/19/2011   Jipmer Physiologist                  1
Discussion topics     Introduction     Myocyte- structure, development     Muscle proteins     Sarcomere     Sarcotub...
Introduction  Human body contains over 400 skeletal muscles     40-50% of total body weight Functions of skeletal muscle...
Skeletal Muscle Characteristics     Most are attached by tendons to bones     Cells are multinucleate     Striated – have ...
Terms              Sarcolemma = Cell membrane              Sarcoplasm = Cytoplasm              Sarcoplasmic Reticulum =...
Structure of skeletal muscle:              connective tissue covering  Epimysium     Surrounds entire muscle  Perimysiu...
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Skeletal muscle structure                                     Composed of muscle cells (fibers),                         ...
•Develop from myoblasts;                                   numbers remain constant                                   •Stri...
Embryologic origin:11/19/2011   Jipmer Physiologist   11
Muscle fiber anatomy      Sarcolemma - cell membrane         Surrounds the sarcoplasm (cytoplasm of fiber)             ...
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Muscle proteins Contractile proteins  Actin- thin myofiliment  Myosin- thick filament Regulatory proteins  Tropomyosin ...
Structure of Actin and Myosin11/19/2011   Jipmer Physiologist   16
   Thin Filament: composed of 3 major    proteins    1. F (fibrous) actin    2. Tropomyosin                              ...
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   Many elongated myosin molecules                                        shaped like golf clubs.                        ...
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 Sarcomere - repeating functional units of                                 a myofibril                                   ...
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Sarcoplasmic Reticulum (SR) SR is an elaborate, smooth endoplasmic    reticulum       runs longitudinally and surrounds ...
Sarcoplasmic Reticulum (SR)                                           Figure 9.511/19/2011       Jipmer Physiologist      ...
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Muscular Contraction  The sliding filament model     Muscle shortening occurs due to the movement of the      actin fila...
Sliding Filament Theory  Rest – uncharged ATP cross-bridge complex  Excitation-coupling – charged ATP cross-bridge   com...
Sliding Filament Model ofContraction  Thin filaments slide past the thick ones so that the   actin and myosin filaments o...
Cross-Bridge Formation in MuscleContraction11/19/2011   Jipmer Physiologist   31
Myosin ATPase Cycle                                           ADP                                           PiFrom: Stryer...
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EM Shows Different TM positions along the Actin Filament                        Relaxed        Ca-Activated        Rigor  ...
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Excitation-Contraction Coupling                                            Mechanism where an                            ...
Sources of ATP for MuscleContraction11/19/2011   Jipmer Physiologist   37
Energy Sources      ATP provides immediate energy for muscle         contractions from 3 sources              Creatine p...
Energy for Muscle Contraction     Direct phosphorylation             Muscle cells contain creatine             phosphate (...
Energy for Muscle Contraction     Anaerobic glycolysis             Reaction that breaks             down glucose without  ...
Energy for Muscle Contraction     Aerobic Respiration             Series of metabolic             pathways that occur in  ...
11/19/2011   Jipmer Physiologist   ‹#›
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Skeletal muscle structure & function

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Skeletal muscle structure & function

  1. 1. Dr. Dinesh T, Junior resident.11/19/2011 Jipmer Physiologist 1
  2. 2. Discussion topics  Introduction  Myocyte- structure, development  Muscle proteins  Sarcomere  Sarcotubular system  Excitation- contraction coupling  Molecular basis of muscle contraction  Summary  Muscle relaxation  Conclusion11/19/2011 Jipmer Physiologist 2
  3. 3. Introduction  Human body contains over 400 skeletal muscles  40-50% of total body weight Functions of skeletal muscle  Body movement (Locomotion)  Maintenance of posture  Respiration  Diaphragm and intercostal contractions  Communication (Verbal and Facial)  Constriction of organs and vessels  Peristalsis of intestinal tract  Vasoconstriction of b.v. and other structures (pupils)  Production of body heat (Thermogenesis)11/19/2011 Jipmer Physiologist 3
  4. 4. Skeletal Muscle Characteristics Most are attached by tendons to bones Cells are multinucleate Striated – have visible banding Voluntary – subject to conscious control Cells are surrounded and bundled by connective tissue = great force, but tires easilyCopyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings11/19/2011 Jipmer Physiologist Slide 6.3 4
  5. 5. Terms  Sarcolemma = Cell membrane  Sarcoplasm = Cytoplasm  Sarcoplasmic Reticulum = Endoplasmic Reticulum  Sarcosomes = Mitochontria11/19/2011 Jipmer Physiologist 5
  6. 6. Structure of skeletal muscle: connective tissue covering  Epimysium  Surrounds entire muscle  Perimysium  Surrounds bundles of muscle fibers  Endomysium  Surrounds individual muscle fibers11/19/2011 Jipmer Physiologist 6
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  9. 9. Skeletal muscle structure  Composed of muscle cells (fibers), connective tissue, blood vessels, nerves  Fibers are long, cylindrical, and multinucleated  Tend to be smaller diameter in small muscles and larger in large muscles. 1 mm- 4 cm in length11/19/2011 Jipmer Physiologist 9
  10. 10. •Develop from myoblasts; numbers remain constant •Striated appearance •Nuclei are peripherally located11/19/2011 Jipmer Physiologist 10
  11. 11. Embryologic origin:11/19/2011 Jipmer Physiologist 11
  12. 12. Muscle fiber anatomy Sarcolemma - cell membrane  Surrounds the sarcoplasm (cytoplasm of fiber)  Contains many of the same organelles seen in other cells  An abundance of the oxygen-binding protein myoglobin  Punctuated by openings called the transverse tubules (T-tubules)  Narrow tubes that extend into the sarcoplasm at right angles to the surface  Filled with extracellular fluid Myofibrils -cylindrical structures within muscle fiber  Are bundles of protein filaments (=myofilaments)  Two types of myofilaments 1. Actin filaments (thin filaments) 2. Myosin filaments (thick filaments) – At each end of the fiber, myofibrils are anchored to the inner surface of the sarcolemma – When myofibril shortens, muscle shortens (contracts)11/19/2011 Jipmer Physiologist 12
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  15. 15. Muscle proteins Contractile proteins  Actin- thin myofiliment  Myosin- thick filament Regulatory proteins  Tropomyosin  Troponin Attachment proteins  Titin, nebulin, alpha actinin, dystrophin11/19/2011 Jipmer Physiologist 15
  16. 16. Structure of Actin and Myosin11/19/2011 Jipmer Physiologist 16
  17. 17.  Thin Filament: composed of 3 major proteins 1. F (fibrous) actin 2. Tropomyosin Actin (Thin) 3. Troponin Two strands of fibrous (F) actin form a double helix extending the length Myofilaments of the myofilament; attached at either end at sarcomere.  Composed of G actin monomers each of which has a myosin- binding site  Actin site can bind myosin during muscle contraction. Tropomyosin: an elongated protein winds along the groove of the F actin double helix. Troponin is composed of three subunits:  Tn-A : binds to actin  Tn-T :binds to tropomyosin,  Tn-C :binds to calcium ions. 11/19/2011 Jipmer Physiologist 17
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  19. 19.  Many elongated myosin molecules shaped like golf clubs.  Single filament contains roughly 300Myosin (Thick)  myosin molecules Molecule consists of two heavy myosin molecules wound together to form a rodMyofilament portion lying parallel to the myosin myofilament and two heads that extend laterally.  Myosin heads 1. Can bind to active sites on the actin molecules to form cross-bridges. (Actin binding site) 2. Attached to the rod portion by a hinge region that can bend and straighten during contraction. 3. Have ATPase activity: activity that breaks down adenosine triphosphate (ATP), releasing energy. Part of the energy is used to bend the hinge region of the myosin molecule during contraction 11/19/2011 Jipmer Physiologist 19
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  21. 21.  Sarcomere - repeating functional units of a myofibril  About 10,000 sarcomeres perSarcomeres: Z Disk myofibril, end to end  Each is about 2 µm longto Z Disk  Differences in size, density, and distribution of thick and thin filaments gives the muscle fiber a banded or striated appearance.  A bands: a dark band; full length of thick (myosin) filament  M line - protein to which myosins attach  H zone - thick but NO thin filaments  I bands: a light band; from Z disks to ends of thick filaments  Thin but NO thick filaments  Extends from A band of one sarcomere to A band of the next sarcomere  Z disk: filamentous network of protein. Serves as attachment for actin myofilaments  Titin filaments: elastic chains of amino acids; keep thick and thin filaments in proper alignment11/19/2011 Jipmer Physiologist 21
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  24. 24. Sarcoplasmic Reticulum (SR) SR is an elaborate, smooth endoplasmic reticulum  runs longitudinally and surrounds each myofibril  Form chambers called terminal cisternae on either side of the T-tubules A single T-tubule and the 2 terminal cisternae form a triad SR stores Ca++ when muscle not contracting  When stimulated, calcium released into sarcoplasm  SR membrane has Ca++ pumps that function to pump Ca++ out of the sarcoplasm back into the SR after contraction11/19/2011 Jipmer Physiologist 24
  25. 25. Sarcoplasmic Reticulum (SR) Figure 9.511/19/2011 Jipmer Physiologist 25
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  28. 28. Muscular Contraction  The sliding filament model  Muscle shortening occurs due to the movement of the actin filament over the myosin filament  Formation of cross-bridges between actin and myosin filaments  Reduction in the distance between Z-lines of the sarcomere11/19/2011 Jipmer Physiologist 28
  29. 29. Sliding Filament Theory  Rest – uncharged ATP cross-bridge complex  Excitation-coupling – charged ATP cross-bridge complex, “turned on”  Contraction – actomyosin – ATP > ADP & Pi + energy  Recharging – reload cross-bridge with ATP  Relaxation – cross-bridges “turned off”11/19/2011 Jipmer Physiologist 29
  30. 30. Sliding Filament Model ofContraction  Thin filaments slide past the thick ones so that the actin and myosin filaments overlap to a greater degree  In the relaxed state, thin and thick filaments overlap only slightly  Upon stimulation, myosin heads bind to actin and sliding begins11/19/2011 Jipmer Physiologist 30
  31. 31. Cross-Bridge Formation in MuscleContraction11/19/2011 Jipmer Physiologist 31
  32. 32. Myosin ATPase Cycle ADP PiFrom: Stryer 1988. Biochemistry. Freeman eds. Based on:Lymn and Taylor. 1971. Biochemistry 10: Jipmer Physiologist 11/19/2011 4617 32
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  34. 34. EM Shows Different TM positions along the Actin Filament Relaxed Ca-Activated Rigor Ca-Activated X-bridgeFrom: Craig & Lehman.. 2001. J. Mol. Biol 311: 1027. 11/19/2011 Jipmer Physiologist 34
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  36. 36. Excitation-Contraction Coupling  Mechanism where an action potential causes muscle fiber contraction  Involves  Sarcolemma  Transverse or T tubules  Terminal cisternae  Sarcoplasmic reticulum  Ca2+  Troponin11/19/2011 Jipmer Physiologist 36
  37. 37. Sources of ATP for MuscleContraction11/19/2011 Jipmer Physiologist 37
  38. 38. Energy Sources  ATP provides immediate energy for muscle contractions from 3 sources  Creatine phosphate  During resting conditions stores energy to synthesize ATP  Anaerobic respiration  Occurs in absence of oxygen and results in breakdown of glucose to yield ATP and lactic acid  Aerobic respiration  Requires oxygen and breaks down glucose to produce ATP, carbon dioxide and water  More efficient than anaerobic11/19/2011 Jipmer Physiologist 38
  39. 39. Energy for Muscle Contraction Direct phosphorylation Muscle cells contain creatine phosphate (CP) CP is a high-energy molecule After ATP is depleted, ADP is left CP transfers energy to ADP, to regenerate ATP CP supplies are exhausted in about 20 seconds11/19/2011 Jipmer Physiologist Figure 6.10a Slide 6.24Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 39
  40. 40. Energy for Muscle Contraction Anaerobic glycolysis Reaction that breaks down glucose without oxygen Glucose is broken down to pyruvic acid to produce some ATP Pyruvic acid is converted to lactic acid11/19/2011 Jipmer Physiologist Figure 6.10bCopyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 40
  41. 41. Energy for Muscle Contraction Aerobic Respiration Series of metabolic pathways that occur in the mitochondria Glucose is broken down to carbon dioxide and water, releasing energy This is a slower reaction that requires continuous oxygen11/19/2011 Jipmer Physiologist Figure 6.10c Slide 6.25Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings 41
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