The document discusses the molecular mechanism of muscle contraction. It describes how skeletal muscle contraction occurs through the sliding filament mechanism, in which actin filaments slide along myosin filaments. This is driven by cross-bridge cycling, where the myosin head attaches to actin and produces a power stroke that pulls the filaments together. Essential requirements for cross-bridge cycling include calcium ions, magnesium ions, and ATP hydrolysis.

1. 11
Muscle Physiology
Prof. Dr. Rashid Mahmood
Contractile Mechanism of Skeletal Muscle II
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood
Video of Myosin Filament Physiology

2. ObjectivesObjectives
Goal/Aim (Main Objective):
To explain the mechanism of muscle contraction
At the end of this lecture students will be able toAt the end of this lecture students will be able to
•Describe Sliding Filament Mechanism ofSliding Filament Mechanism of
Muscle ContractionMuscle Contraction
•Outline the stages/ steps of Cross BridgeCross Bridge
CycleCycle
•Explain Walk-along theoryWalk-along theory
(Ratchet theory)(Ratchet theory)
•Describe Chemical events in the motion ofChemical events in the motion of
myosin headsmyosin heads

3. Lesson contents
Review of structure of Actin & Myosin FilamentReview of structure of Actin & Myosin Filament
Molecular mechanism of muscle contractionMolecular mechanism of muscle contraction
Sliding Filament MechanismSliding Filament Mechanism
Cross Bridge ActivityCross Bridge Activity
Cross Bridge CycleCross Bridge Cycle
Role of Calcium in Cross-Bridge CycleRole of Calcium in Cross-Bridge Cycle
Interaction of myosin and actin filamentInteraction of myosin and actin filament
Walk-along theory (Ratchet theory)Walk-along theory (Ratchet theory)
Chemical events in the motion of myosin headsChemical events in the motion of myosin heads
33Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

4. 44
MolecularMolecular
mechanism ofmechanism of
musclemuscle
contractioncontraction
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

5. 55
Review of structure of MyosinReview of structure of Myosin
FilamentFilament
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

6. 66
Actin HelixActin Helix
+ tropomyosin+ tropomyosin
+troponin+troponin
==
Actin FilamentActin Filament
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood
Review of
structure of
Actin
Filament

7. 77
Molecular Basis of Skeletal Muscle ContractionMolecular Basis of Skeletal Muscle Contraction
(Sliding Filament Mechanism)(Sliding Filament Mechanism)
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

8. 88
Sliding filament of muscleSliding filament of muscle
contractioncontraction
Under resting condition, attractive forces are inactive
Energy comes from ATP → degraded to ADP

10. Assessment Q. 1Assessment Q. 1
What is meant by Molecular Basis ofWhat is meant by Molecular Basis of
Skeletal Muscle Contraction?Skeletal Muscle Contraction?
1010Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

11. 1111
Cross Bridge ActivityCross Bridge Activity
Rise in intracellular calcium ion Concentration triggersRise in intracellular calcium ion Concentration triggers
cross bridge activitycross bridge activity Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

12. 1212
Cross Bridge CycleCross Bridge Cycle
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

13. 1313Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

14. Cross Bridge CycleCross Bridge Cycle

15. 1515
Cross Bridge CycleCross Bridge Cycle
1
2
3
4
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

16. Role of Calcium in Cross-Bridge CycleRole of Calcium in Cross-Bridge Cycle
During relaxed stateDuring relaxed state

17. Role of Calcium in Cross-Bridge CycleRole of Calcium in Cross-Bridge Cycle
ExcitedExcited

18. 1818
Interaction of myosin and actinInteraction of myosin and actin
filament (Roll of Ca++)filament (Roll of Ca++)
A pure actin filamentA pure actin filament withoutwithout thethe
presence ofpresence of troponin-tropomyosintroponin-tropomyosin
complex bindscomplex binds instantlyinstantly with andwith and
stronglystrongly with heads of myosin filaments,with heads of myosin filaments,
in the presence ofin the presence of Mg++Mg++ andand ATPATP
Binding does not occur ifBinding does not occur if troponin-troponin-
tropomyosintropomyosin complex is added to actincomplex is added to actin
filamentfilament
Active sites areActive sites are coveredcovered/ inhibited by/ inhibited by
troponin-tropomyosintroponin-tropomyosin complexcomplex
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

19. 1919
Active site are covered/ inhibited byActive site are covered/ inhibited by
troponin-tropomyosin complextroponin-tropomyosin complex
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

20. Assessment Q. 2Assessment Q. 2
Name the ions essential for SkeletalName the ions essential for Skeletal
Muscle ContractionMuscle Contraction
2020Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

21. 2121
Walk-along theoryWalk-along theory
(Ratchet theory)(Ratchet theory)
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

22. 2222
Walk-along theoryWalk-along theory
(Ratchet theory)(Ratchet theory)
UncoveringUncovering of active sites →of active sites →
headsheads attractedattracted towards and attach with active sitestowards and attach with active sites
→→
change in intermolecular forces between head andchange in intermolecular forces between head and
arm →arm →
headhead tiltstilts andand dragsdrags actin filament along with it →actin filament along with it →
calledcalled POWER STROKEPOWER STROKE
→→after tilting automaticallyafter tilting automatically breaksbreaks andand returnsreturns toto
extended direction →extended direction →combinescombines withwith aa newnew active siteactive site
→→
again tiltsagain tilts (NEW(NEW POWERPOWER STROKE)STROKE) →→
againagain and againand again
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

23. Walk-along theoryWalk-along theory
(Ratchet theory)(Ratchet theory)

24. Assessment Q. 3Assessment Q. 3
Define “Ratchet Theory of MuscleDefine “Ratchet Theory of Muscle
Contraction”Contraction”
2424Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

25. Chemical events in theChemical events in the
motion of myosin headsmotion of myosin heads
2525Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

26. 2626
Cross Bridge Cycle, showing Chemical eventsCross Bridge Cycle, showing Chemical events
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

27. 2727
Chemical events in the motionChemical events in the motion
of myosin headsof myosin heads
energy comes from high-energy bondsenergy comes from high-energy bonds
in thein the ATPATP molecule, which is degradedmolecule, which is degraded
to adenosine diphosphateto adenosine diphosphate (ADP)(ADP) toto
liberate the energyliberate the energy
greater the amount of work performedgreater the amount of work performed
by the muscle, the greater the amountby the muscle, the greater the amount
of ATP that is cleaved, which is calledof ATP that is cleaved, which is called
thethe Fenn effectFenn effect
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

28. 2828
Sequence of eventsSequence of events
Before contraction beginsBefore contraction begins, the heads of the cross-, the heads of the cross-
bridgesbridges bind with ATPbind with ATP..
The ATPase activity of the myosin head immediatelyThe ATPase activity of the myosin head immediately
cleavescleaves thethe ATPATP butbut leavesleaves thethe cleavagecleavage productsproducts,,
ADP plus phosphate ion,ADP plus phosphate ion, boundbound to the head.to the head.
In this state, head extendsIn this state, head extends perpendicularlyperpendicularly towardtoward
the actin filament but isthe actin filament but is notnot yetyet attachedattached to the actin.to the actin.
When the troponin-tropomyosin complex bindsWhen the troponin-tropomyosin complex binds
withwith calciumcalcium ions, active sites on the actin filamentions, active sites on the actin filament
areare uncovereduncovered, and the myosin heads then bind with, and the myosin heads then bind with
thesethese →→
conformational change in the head, prompting theconformational change in the head, prompting the
head tohead to tilttilt toward the arm of the cross-bridgetoward the arm of the cross-bridge
The energy that activates theThe energy that activates the powerpower strokestroke is theis the
energyenergy alreadyalready storedstored, like a ", like a "cockedcocked"" springspring
Contd…
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

29. 2929
Sequence of eventsSequence of events
this allowsthis allows releaserelease of the ADP and phosphateof the ADP and phosphate
ionion
At the site of release of the ADP, aAt the site of release of the ADP, a newnew
molecule ofmolecule of ATPATP binds →binds →
detachmentdetachment of the head →of the head →
new molecule of ATP is cleaved to begin thenew molecule of ATP is cleaved to begin the
nextnext cyclecycle→→
newnew powerpower strokestroke
energy again "cocks”energy again "cocks”
againagain and againand again
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

30. 3030
SequenceSequence
of eventsof events
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

31. Points to ponder (Summary)Points to ponder (Summary)
Molecular mechanism of muscle contraction includes interaction of Actin & MyosinMolecular mechanism of muscle contraction includes interaction of Actin & Myosin
FilamentsFilaments
Sliding Filament Mechanism refers to sliding of actin filaments on myosin filamentsSliding Filament Mechanism refers to sliding of actin filaments on myosin filaments
Cross Bridge Cycle means one cycle of attachment of Cross-bridge with its bindingCross Bridge Cycle means one cycle of attachment of Cross-bridge with its binding
site on Actin filament followed by its detachmentsite on Actin filament followed by its detachment
Detachment of myosin from actin does not mean necessarily mean the relaxation ofDetachment of myosin from actin does not mean necessarily mean the relaxation of
the muscle; it starts another cross-bridge cyclethe muscle; it starts another cross-bridge cycle
Essential requirements for Cross-Bridge Cycle include Calcium , Mg++ and ATPEssential requirements for Cross-Bridge Cycle include Calcium , Mg++ and ATP
Interaction of myosin and actin filament resulting in muscle shortening is bestInteraction of myosin and actin filament resulting in muscle shortening is best
explained by Walk-along theory (Ratchet theory)explained by Walk-along theory (Ratchet theory)
Tilting of the head that drags actin filament along with it requires energy & is calledTilting of the head that drags actin filament along with it requires energy & is called
Power StrokePower Stroke
Chemical events in the motion of myosin heads include cleavage of ATP; theChemical events in the motion of myosin heads include cleavage of ATP; the
essential step for detachment of myosin from actin i.e. before contraction beginsessential step for detachment of myosin from actin i.e. before contraction begins
The energy that activates the power stroke is the energy already stored, like aThe energy that activates the power stroke is the energy already stored, like a
"cocked" spring"cocked" spring
At the site of release of the ADP, a new molecule of ATP binds , resulting inAt the site of release of the ADP, a new molecule of ATP binds , resulting in
detachment of the headdetachment of the head
Greater the amount of work performed by the muscle, the greater the amount ofGreater the amount of work performed by the muscle, the greater the amount of
ATP that is cleaved, which is called the Fenn effectATP that is cleaved, which is called the Fenn effect
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32. Learning ResourcesLearning Resources
Guyton and Hall (Text book ofGuyton and Hall (Text book of
physiology), 13th Editionphysiology), 13th Edition
Ganong (Text book of physiology),Ganong (Text book of physiology),
24th Edition24th Edition
Human Physiology : from cells toHuman Physiology : from cells to
system Lauralee Sherwood,9system Lauralee Sherwood,9thth
EditionEdition
Human Physiology Stuart Ira Fox, 13thHuman Physiology Stuart Ira Fox, 13th
EditionEdition
InternetInternet Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood3232

33. Next topic
Energetics of muscle contraction
Wed, 18/01/2017, 1200 pm: 0100 pm
Prior knowledge required: Contractile
Mechanism of Skeletal Muscle
3333Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

34. Assessment Q. 4Assessment Q. 4
What are the Essential chemicalsWhat are the Essential chemicals
required for Cross-Bridge Cycle?required for Cross-Bridge Cycle?

35. ANY QUESTIONS?
Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood3535