contractile mechanism of skeletal muscle 2

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Muscle Physiology

Prof. Dr. Rashid Mahmood

Contractile Mechanism of Skeletal Muscle II

Prof. Dr. Rashid MahmoodProf. Dr. Rashid MahmoodVideo of Myosin Filament Physiology

Objectives Objectives Goal/Aim (Main Objective): To explain the mechanism of muscle contractionAt the end of this lecture students will be able toAt the end of this lecture students will be able to•Describe Sliding Filament Mechanism of Muscle Contraction Sliding Filament Mechanism of Muscle Contraction •Outline the stages/ steps of Cross Bridge CycleCross Bridge Cycle•Explain Walk-along theory Walk-along theory (Ratchet theory)(Ratchet theory)•Describe Chemical events in the motion of myosin heads Chemical events in the motion of myosin heads

Lesson contentsReview of structure of Actin & Myosin Review of structure of Actin & Myosin FilamentFilamentMolecular mechanism of muscle contraction Molecular mechanism of muscle contraction Sliding Filament MechanismSliding Filament MechanismCross Bridge Activity Cross Bridge Activity Cross Bridge CycleCross Bridge CycleRole of Calcium in Cross-Bridge CycleRole of Calcium in Cross-Bridge CycleInteraction of myosin and actin filamentInteraction of myosin and actin filamentWalk-along theory (Ratchet theory)Walk-along theory (Ratchet theory)Chemical events in the motion of myosin Chemical events in the motion of myosin headsheads

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Molecular Molecular mechanism of mechanism of

muscle muscle contraction contraction

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Review of structure of Review of structure of Myosin FilamentMyosin Filament


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Actin HelixActin Helix+ +

tropomyositropomyosinn

+troponin+troponin= =

Actin Actin FilamentFilament


Review of structure of ActinFilament

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Molecular Basis of Skeletal Muscle Molecular Basis of Skeletal Muscle Contraction (Sliding Filament Contraction (Sliding Filament

Mechanism)Mechanism)


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Sliding filament of muscle Sliding filament of muscle contraction contraction

Under resting condition, attractive forces are inactive

Energy comes from ATP → degraded to ADP

Assessment Q. 1Assessment Q. 1What is meant by Molecular Basis What is meant by Molecular Basis of Skeletal Muscle Contraction?of Skeletal Muscle Contraction?


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Cross Bridge Activity Cross Bridge Activity

Rise in intracellular calcium ion Concentration Rise in intracellular calcium ion Concentration triggers cross bridge activitytriggers cross bridge activityProf. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

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Cross Bridge CycleCross Bridge Cycle


Cross Bridge CycleCross Bridge Cycle

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Cross Bridge CycleCross Bridge Cycle1

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Role of Calcium in Cross-Role of Calcium in Cross-Bridge CycleBridge Cycle

During relaxed state During relaxed state

Role of Calcium in Cross-Role of Calcium in Cross-Bridge CycleBridge Cycle

Excited Excited

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Interaction of myosin and Interaction of myosin and actin filament (Roll of Ca+actin filament (Roll of Ca+

+)+)A pure actin filament A pure actin filament without without the the presence of presence of troponin-tropomyosintroponin-tropomyosin complex binds complex binds instantlyinstantly with and with and stronglystrongly with heads of myosin with heads of myosin filaments, in the presence of filaments, in the presence of Mg++Mg++ and and ATPATP Binding does not occur if Binding does not occur if troponin-troponin-tropomyosintropomyosin complex is added to actin complex is added to actin filament filament Active sites are Active sites are coveredcovered/ inhibited by / inhibited by troponin-tropomyosintroponin-tropomyosin complex complex Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood

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Active site are covered/ Active site are covered/ inhibited by troponin-inhibited by troponin-tropomyosin complex tropomyosin complex


Assessment Q. 2Assessment Q. 2Name the ions essential for Name the ions essential for Skeletal Muscle ContractionSkeletal Muscle Contraction


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Walk-along theory Walk-along theory (Ratchet theory)(Ratchet theory)


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UncoveringUncovering of active sites → of active sites →headsheads attractedattracted towards and attach with active towards and attach with active sites →sites →change in intermolecular forces between head change in intermolecular forces between head and arm →and arm →headhead tiltstilts and and dragsdrags actin filament along with it → actin filament along with it →called called POWER STROKEPOWER STROKE → →after tilting automatically after tilting automatically breaksbreaks and and returnsreturns to to extended direction →extended direction →combinescombines withwith aa newnew active active site →site →again tilts again tilts (NEW(NEW POWERPOWER STROKE)STROKE) → →againagain and again and again


Assessment Q. 3Assessment Q. 3Define “Ratchet Theory of Muscle Define “Ratchet Theory of Muscle Contraction”Contraction”


Chemical events in the Chemical events in the motion of myosin headsmotion of myosin heads


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Cross Bridge Cycle, showing Chemical Cross Bridge Cycle, showing Chemical eventsevents


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Chemical events in the Chemical events in the motion of myosin headsmotion of myosin headsenergy comes from high-energy energy comes from high-energy bonds in the bonds in the ATP ATP molecule, which is molecule, which is degraded to degraded to adenosine diphosphate diphosphate (ADP)(ADP) to liberate the energy to liberate the energy greater the amount of work greater the amount of work performed by the muscle, the greater performed by the muscle, the greater the amount of ATP that is cleaved, the amount of ATP that is cleaved, which is called the which is called the Fenn effectFenn effect


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Sequence of events Sequence of events Before contraction beginsBefore contraction begins, the heads of the cross-, the heads of the cross-bridges bridges bind with ATPbind with ATP. . The ATPase activity of the myosin head The ATPase activity of the myosin head immediately immediately cleavescleaves thethe ATPATP but but leavesleaves thethe cleavagecleavage productsproducts, ADP plus phosphate ion, , ADP plus phosphate ion, boundbound to the head. to the head. In this state, head extends In this state, head extends perpendicularlyperpendicularly toward the actin filament but is toward the actin filament but is notnot yetyet attachedattached to the actin.to the actin. When the troponin-tropomyosin complex binds When the troponin-tropomyosin complex binds with with calciumcalcium ions, active sites on the actin ions, active sites on the actin filament are filament are uncovereduncovered, and the myosin heads , and the myosin heads then bind with these then bind with these →→ conformational change in the head, prompting conformational change in the head, prompting the head to the head to tilttilt toward the arm of the cross-bridge toward the arm of the cross-bridge The energy that activates the The energy that activates the powerpower strokestroke is the is the energy energy alreadyalready storedstored, like a ", like a "cockedcocked" " springspring

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Sequence of eventsSequence of eventsthis allows this allows releaserelease of the ADP and of the ADP and phosphate ion phosphate ion At the site of release of the ADP, a At the site of release of the ADP, a newnew molecule of molecule of ATPATP binds → binds →detachmentdetachment of the head → of the head →new molecule of ATP is cleaved to new molecule of ATP is cleaved to begin the begin the nextnext cyclecycle→→ newnew powerpower strokestroke energy again "cocks”energy again "cocks” againagain and again and again


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SequencSequence of e of

eventsevents


Points to ponder (Summary)Points to ponder (Summary)Molecular mechanism of muscle contraction includes interaction of Actin & Molecular mechanism of muscle contraction includes interaction of Actin &

Myosin FilamentsMyosin FilamentsSliding Filament Mechanism refers to sliding of actin filaments on myosin Sliding Filament Mechanism refers to sliding of actin filaments on myosin

filamentsfilamentsCross Bridge Cycle means one cycle of attachment of Cross-bridge with its Cross Bridge Cycle means one cycle of attachment of Cross-bridge with its

binding site on Actin filament followed by its detachmentbinding site on Actin filament followed by its detachmentDetachment of myosin from actin does not mean necessarily mean the Detachment of myosin from actin does not mean necessarily mean the

relaxation of the muscle; it starts another cross-bridge cyclerelaxation of the muscle; it starts another cross-bridge cycleEssential requirements for Cross-Bridge Cycle include Calcium , Mg++ and ATP Essential requirements for Cross-Bridge Cycle include Calcium , Mg++ and ATP Interaction of myosin and actin filament resulting in muscle shortening is best Interaction 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 Tilting of the head that drags actin filament along with it requires energy & is

called Power Strokecalled Power StrokeChemical events in the motion of myosin heads include cleavage of ATP; the Chemical events in the motion of myosin heads include cleavage of ATP; the

essential step for detachment of myosin from actin i.e. before contraction essential step for detachment of myosin from actin i.e. before contraction beginsbeginsThe energy that activates the power stroke is the energy already stored, like a The energy that activates the power stroke is the energy already stored, like a

"cocked" spring"cocked" springAt the site of release of the ADP, a new molecule of ATP binds , resulting in At the site of release of the ADP, a new molecule of ATP binds , resulting in

detachment of the head detachment of the head Greater the amount of work performed by the muscle, the greater the amount Greater the amount of work performed by the muscle, the greater the amount

of ATP that is cleaved, which is called the Fenn effect of ATP that is cleaved, which is called the Fenn effect 3131

Learning ResourcesLearning ResourcesGuyton and Hall (Text book of physiology), Guyton and Hall (Text book of physiology), 13th Edition13th EditionGanong (Text book of physiology), 24th Ganong (Text book of physiology), 24th EditionEditionHuman Physiology : from cells to system Human Physiology : from cells to system Lauralee Sherwood,9Lauralee Sherwood,9thth Edition Edition Human Physiology Stuart Ira Fox, 13th Human Physiology Stuart Ira Fox, 13th EditionEditionInternetInternet

Prof. Dr. Rashid MahmoodProf. Dr. Rashid Mahmood3232

Next topicEnergetics of muscle contractionWed, 18/01/2017, 1200 pm: 0100 pmPrior knowledge required: Contractile Mechanism of Skeletal Muscle


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

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

contractile mechanism of skeletal muscle 2

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