Anatomy and Physiology

   Sliding Filament Model
Excitation-Contraction
                 Coupling
                                                            Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.




• Muscle impulses cause SR to                                                                                                                      Tropomyosin
                                                                                                                                                   Troponin                  Thin filament

release calcium ions into cytosol                                                    ADP P
                                                                                         +                 ADP P
                                                                                                               +
                                                                                                                                                   Actin monomers



• Calcium binds to troponin to
                                                                                                                                                   Thick filament
                                                                        1 Relaxed muscle
                                             Muscle contraction                                                                     Muscle relaxation
change its shape                                                                     Ca+2                               Ca+2
                                    Release of Ca from sarcoplasmic
                                                  +2
                                                                                                                     Active transport of Ca+2 into sarcoplasmic
                                    reticulum exposes binding sites on actin:                                        reticulum, which requires ATP, makes
• The position of tropomyosin is               Ca+2 binds to troponin
                                                                                                                     myosin binding sites unavailable.
                                                                                                                     ATP
                                             Tropomyosin pulled aside

altered                                        Binding sites on
                                               actin exposed

• Binding sites on actin are now                                               Ca+2
                                                                                  ADP +
                                                                                      P
                                                                                                       Ca+2
                                                                                                        ADP P
                                                                                                            +
                                                                                                                              Ca+2



exposed                                                                 2 Exposed binding sites on actin molecules
                                                                          allow the muscle contraction cycle to occur

• Actin and myosin molecules bind
via myosin cross-bridges                      ADP P
                                                  +       ADP +
                                                              P                               Contraction cycle                                ADP +
                                                                                                                                                   P                 ADP +
                                                                                                                                                                         P


                                      6 ATP splits, which provides                                                             3 Cross-bridges bind actin to
                                        power to “cock” the myosin                                                               myosin
                                        cross-bridges




                                                                                                                                                               ADP           ADP
                                            ATP          ATP             ATP                                                                               P            P
                                                                              ATP   ADP +P
                                      5 New ATP binds to myosin, releasing linkages                                            4 Cross-bridges pull thin filament
                                                                                                                                 (power stroke), ADP and P released
                                                                                                                                 from myosin
                                                                                                                                                                                     2
The Sliding Filament Model
       of Muscle Contraction
                           Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.


• When sarcromeres                                                  Sarcomere



shorten, thick and thin                  Z line
                                                                     A band
                                                                                                       Z line


filaments slide past one
another
• H zones and I bands
narrow
                                                                      1 Relaxed
                                                 Thin                                          Thick
                                              filaments                                     filaments

• Z lines move closer
together
                                                                      2 Contracting




                                                                                                                          3
                                                                      3 Fully contracted
                                       (a)
Cross Bridge Cycling
• Myosin cross-bridge attaches
to actin binding site                                     Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.




• Myosin cross-bridge pulls
                                                                                                                                                 Tropomyosin
                                                                                                                                                 Troponin                  Thin filament
                                                                                                                                                 Actin monomers

thin filament                                                                      ADP P
                                                                                       +                 ADP P
                                                                                                             +
                                                                                                                                                 Thick filament
                                                                      1 Relaxed muscle

• ADP and phosphate                        Muscle contraction
                                  Release of Ca from sarcoplasmic
                                                +2
                                                                                   Ca+2                               Ca+2
                                                                                                                                  Muscle relaxation
                                                                                                                   Active transport of Ca+2 into sarcoplasmic

released from myosin              reticulum exposes binding sites on actin:

                                             Ca+2 binds to troponin
                                                                                                                   reticulum, which requires ATP, makes
                                                                                                                   myosin binding sites unavailable.
                                                                                                                   ATP
                                           Tropomyosin pulled aside

• New ATP binds to myosin                    Binding sites on
                                             actin exposed

                                                                             Ca+2                    Ca+2                   Ca+2
                                                                                ADP +
                                                                                    P                 ADP P
                                                                                                          +

                                                                      2 Exposed binding sites on actin molecules
• Linkage between actin and                                             allow the muscle contraction cycle to occur



myosin cross-bridge break
                                            ADP P
                                                +       ADP +
                                                            P                               Contraction cycle                                ADP +
                                                                                                                                                 P                 ADP +
                                                                                                                                                                       P


                                    6 ATP splits, which provides                                                             3 Cross-bridges bind actin to
                                      power to “cock” the myosin                                                               myosin
• ATP splits                          cross-bridges




• Myosin cross-bridge goes back           ATP          ATP             ATP                                                                               P
                                                                                                                                                             ADP
                                                                                                                                                                      P
                                                                                                                                                                           ADP

                                                                            ATP   ADP +P
to original position                5 New ATP binds to myosin, releasing linkages                                            4 Cross-bridges pull thin filament
                                                                                                                               (power stroke), ADP and P released
                                                                                                                               from myosin
                                                                                                                                                                                   4
Animation: The Cross-Bridge Cycle



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                                                    5
Animation: Breakdown of ATP
 and Cross-Bridge Movement



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                                                  6
Relaxation
• Acetylcholinesterase – rapidly decomposes Ach remaining in
the synapse
• Muscle impulse stops
• Stimulus to sarcolemma and muscle fiber membrane ceases
• Calcium moves back into sarcoplasmic reticulum (SR)
• Myosin and actin binding prevented
• Muscle fiber relaxes


                                                            7
References
• Shier, D., Butler, J., and Lewis, R. 2010.
  Hole’s Human Anatomy & Physiology, New
  York.




                                           8

Sliding Filament Model of Muscle Contraction

  • 1.
    Anatomy and Physiology Sliding Filament Model
  • 2.
    Excitation-Contraction Coupling Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Muscle impulses cause SR to Tropomyosin Troponin Thin filament release calcium ions into cytosol ADP P + ADP P + Actin monomers • Calcium binds to troponin to Thick filament 1 Relaxed muscle Muscle contraction Muscle relaxation change its shape Ca+2 Ca+2 Release of Ca from sarcoplasmic +2 Active transport of Ca+2 into sarcoplasmic reticulum exposes binding sites on actin: reticulum, which requires ATP, makes • The position of tropomyosin is Ca+2 binds to troponin myosin binding sites unavailable. ATP Tropomyosin pulled aside altered Binding sites on actin exposed • Binding sites on actin are now Ca+2 ADP + P Ca+2 ADP P + Ca+2 exposed 2 Exposed binding sites on actin molecules allow the muscle contraction cycle to occur • Actin and myosin molecules bind via myosin cross-bridges ADP P + ADP + P Contraction cycle ADP + P ADP + P 6 ATP splits, which provides 3 Cross-bridges bind actin to power to “cock” the myosin myosin cross-bridges ADP ADP ATP ATP ATP P P ATP ADP +P 5 New ATP binds to myosin, releasing linkages 4 Cross-bridges pull thin filament (power stroke), ADP and P released from myosin 2
  • 3.
    The Sliding FilamentModel of Muscle Contraction Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • When sarcromeres Sarcomere shorten, thick and thin Z line A band Z line filaments slide past one another • H zones and I bands narrow 1 Relaxed Thin Thick filaments filaments • Z lines move closer together 2 Contracting 3 3 Fully contracted (a)
  • 4.
    Cross Bridge Cycling •Myosin cross-bridge attaches to actin binding site Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Myosin cross-bridge pulls Tropomyosin Troponin Thin filament Actin monomers thin filament ADP P + ADP P + Thick filament 1 Relaxed muscle • ADP and phosphate Muscle contraction Release of Ca from sarcoplasmic +2 Ca+2 Ca+2 Muscle relaxation Active transport of Ca+2 into sarcoplasmic released from myosin reticulum exposes binding sites on actin: Ca+2 binds to troponin reticulum, which requires ATP, makes myosin binding sites unavailable. ATP Tropomyosin pulled aside • New ATP binds to myosin Binding sites on actin exposed Ca+2 Ca+2 Ca+2 ADP + P ADP P + 2 Exposed binding sites on actin molecules • Linkage between actin and allow the muscle contraction cycle to occur myosin cross-bridge break ADP P + ADP + P Contraction cycle ADP + P ADP + P 6 ATP splits, which provides 3 Cross-bridges bind actin to power to “cock” the myosin myosin • ATP splits cross-bridges • Myosin cross-bridge goes back ATP ATP ATP P ADP P ADP ATP ADP +P to original position 5 New ATP binds to myosin, releasing linkages 4 Cross-bridges pull thin filament (power stroke), ADP and P released from myosin 4
  • 5.
    Animation: The Cross-BridgeCycle Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 5
  • 6.
    Animation: Breakdown ofATP and Cross-Bridge Movement Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 6
  • 7.
    Relaxation • Acetylcholinesterase –rapidly decomposes Ach remaining in the synapse • Muscle impulse stops • Stimulus to sarcolemma and muscle fiber membrane ceases • Calcium moves back into sarcoplasmic reticulum (SR) • Myosin and actin binding prevented • Muscle fiber relaxes 7
  • 8.
    References • Shier, D.,Butler, J., and Lewis, R. 2010. Hole’s Human Anatomy & Physiology, New York. 8