C H A P T E R 9Muscles and Muscle Physiology

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Table 9.3 Comparison of Skeletal, Cardiac, and Smooth Muscle (1 of 4)

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Special Characteristics of Muscle Tissue

• Excitability:

• Contractility:

• Extensibility:

• Elasticity:

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Muscle Functions

• Four important functions– Movement of bones or fluids (e.g., blood)– Maintaining posture and body position – Stabilizing joints– Heat generation (especially skeletal muscle)

• Additional functions– Protects organs, forms valves, controls pupil

size, causes "goosebumps"

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Figure 9.1 Connective tissue sheaths of skeletal muscle: epimysium, perimysium, and endomysium.

Bone

Tendon

Epimysium Epimysium

Perimysium

Endomysium

Muscle fiberin middle of a fascicle

Blood vesselPerimysiumwrapping a fascicleEndomysium(between individualmuscle fibers)

Musclefiber

Perimysium

Fascicle

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Skeletal Muscle: Attachments

• Attach in at least two places– Insertion – movable bone– Origin – immovable (less movable) bone

• Attachments direct or indirect– Direct—epimysium fused to periosteum of

bone or perichondrium of cartilage– Indirect—connective tissue wrappings extend

beyond muscle as ropelike tendon or sheetlike aponeurosis

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Table 9.1 Structure and Organizational Levels of Skeletal Muscle (1 of 3)

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Table 9.1 Structure and Organizational Levels of Skeletal Muscle (2 of 3)

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Figure 9.2b Microscopic anatomy of a skeletal muscle fiber.

Diagram of part of a muscle fiber showingthe myofibrils. One myofibril extends from the cut end of the fiber.

Sarcolemma

Mitochondrion

MyofibrilNucleusLight

I bandDark

A band

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Myofibrils

• Densely packed, rodlike elements • ~80% of cell volume • Contain sarcomeres - contractile units

– Sarcomeres contain myofilaments• Exhibit striations - perfectly aligned

repeating series of dark A bands and light I bands

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Figure 9.2c Microscopic anatomy of a skeletal muscle fiber.

Small part of onemyofibril enlarged to show the myofilamentsresponsible for thebanding pattern. Each sarcomere extends from one Z disc to the next.

Thin (actin)filament Z disc H zone Z disc

Thick (myosin)filament

I band A band I band M lineSarcomere

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Striations

• H zone:

• M line:

• Z disc (line):

• Thick filaments:

• Thin filaments:

• Sarcomere:6/24/2012 12

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Figure 9.2c Microscopic anatomy of a skeletal muscle fiber.

Small part of onemyofibril enlarged to show the myofilamentsresponsible for thebanding pattern. Each sarcomere extends from one Z disc to the next.

Thin (actin)filament Z disc H zone Z disc

Thick (myosin)filament

I band A band I band M lineSarcomere

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Figure 9.2d Microscopic anatomy of a skeletal muscle fiber.

Enlargement of one sarcomere (sectioned length-wise). Notice themyosin heads on the thick filaments.

Z discSarcomere

M line Z disc Thin (actin)filamentElastic (titin)filamentsThick(myosin)filament

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Longitudinal section of filaments within onesarcomere of a myofibril

Thick filamentThin filament

In the center of the sarcomere, the thick filamentslack myosin heads. Myosin heads are present onlyin areas of myosin-actin overlap.

Thick filament. Thin filamentEach thick filament consists of many myosin

molecules whose heads protrude at oppositeends of the filament.

A thin filament consists of two strands of actinsubunits twisted into a helix plus two types of

regulatory proteins (troponin and tropomyosin).Portion of a thick filament Portion of a thin filament

Myosin head Tropomyosin Troponin Actin

Actin-binding sites

ATP-bindingsite

Heads Tail

Flexible hinge region

Myosin molecule

Actin subunits

Actin subunits

Active sitesfor myosinattachment

Figure 9.3 Composition of thick and thin filaments.

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Figure 9.5 Relationship of the sarcoplasmic reticulum and T tubules to myofibrils of skeletal muscle.

Part of a skeletal muscle fiber (cell)

Myofibril

Sarcolemma

I band A band I band

Z disc H zone Z discM

line

Sarcolemma

Triad:• T tubule• Terminal cisterns of the SR (2)

Tubules ofthe SRMyofibrilsMitochondria

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Sliding Filament Model of Contraction

• Generation of force • Does not necessarily cause shortening of

fiber• Shortening occurs when tension

generated by cross bridges on thin filaments exceeds forces opposing shortening

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Sliding Filament Model of Contraction

• In relaxed state, thin and thick filaments overlap only at ends of A band

• Sliding filament model of contraction– During contraction, thin filaments slide past

thick filaments actin and myosin overlap more

– Occurs when myosin heads bind to actin cross bridges

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Figure 9.6 Sliding filament model of contraction. Slide 1Slide 1

Fully contracted sarcomere of a muscle fiber

1

2

Fully relaxed sarcomere of a muscle fiber

Z H ZII A

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Sliding Filament Model of Contraction

• Myosin heads bind to actin; sliding begins • Cross bridges form and break several

times, ratcheting thin filaments toward center of sarcomere– Causes shortening of muscle fiber– Pulls Z discs toward M line

• I bands shorten; Z discs closer; H zones disappear; A bands move closer (length stays same)

• Review Sliding Filament Theory on IP6/24/2012 20

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Figure 9.6 Sliding filament model of contraction. Slide 4

Fully contracted sarcomere of a muscle fiber

1

2

Fully relaxed sarcomere of a muscle fiber

Z H ZII A

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Physiology of Skeletal Muscle Fibers

• For skeletal muscle to contract– Activation (at neuromuscular junction)

• Must be nervous system stimulation• Must generate action potential in

sarcolemma– Excitation-contraction coupling

• Action potential propagated along sarcolemma

• Intracellular Ca2+ levels must rise briefly

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Figure 9.8 When a nerve impulse reaches a neuromuscular junction, acetylcholine (ACh) is released. Slide 1

Actionpotential (AP)

Myelinated axonof motor neuron

Axon terminal of neuromuscular junction

Sarcolemma ofthe muscle fiber

Synaptic vesiclecontaining ACh

Synaptic cleft

Junctionalfolds of sarcolemma

Sarcoplasm ofmuscle fiber

Postsynaptic membraneion channel opens;ions pass.

Ion channel closes;ions cannot pass.

Action potential arrives at axon terminal of motor neuron.

Voltage-gated Ca2+ channels open. Ca2+ enters the axon terminal moving down its electochemical gradient.

Ca2+ entry causes ACh (aneurotransmitter) to be releasedby exocytosis.

ACh diffuses across the synaptic cleft and binds to its receptors on the sarcolemma.

ACh binding opens ionchannels in the receptors thatallow simultaneous passage ofNa+ into the muscle fiber and K+

out of the muscle fiber. More Na+

ions enter than K+ ions exit,which produces a local changein the membrane potential calledthe end plate potential.

ACh effects are terminated byits breakdown in the synapticcleft by acetylcholinesterase anddiffusion away from the junction.

Axon terminalof motor neuronFusing synaptic vesicles

Degraded AChACh

Acetylcho-linesterase

ACh4

3

2

1

5

6

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Phase 1Motor neuronstimulatesmuscle fiber(see Figure 9.8).

Phase 2:Excitation-contraction coupling occurs (see Figures 9.9 and 9.11).

Action potential (AP) arrives at axonterminal at neuromuscular junction

ACh released; binds to receptorson sarcolemma

Ion permeability of sarcolemma changes

Local change in membrane voltage(depolarization) occurs

Local depolarization (end platepotential) ignites AP in sarcolemma

AP travels across the entire sarcolemma

AP travels along T tubules

SR releases Ca2+; Ca2+ binds totroponin; myosin-binding sites(active sites) on actin exposed

Myosin heads bind to actin;contraction begins

Figure 9.7 The phases leading to muscle fiber contraction.

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Figure 9.9 Summary of events in the generation and propagation of an action potential in a skeletalmuscle fiber.

Slide 1Open Na+

channelNa+

Closed K+

channel

K+

Action potential

Axon terminal ofneuromuscularjunction

ACh-containingsynaptic vesicle

Ca2+Ca2+

Synapticcleft

Wave ofdepolarization

An end plate potential is generated at theneuromuscular junction (see Figure 9.8).

Depolarization: Generating and propagating an actionpotential (AP). The local depolarization current spreads to adjacentareas of the sarcolemma. This opens voltage-gated sodium channelsthere, so Na+ enters following its electrochemical gradient and initiatesthe AP. The AP is propagated as its local depolarization wave spreads toadjacent areas of the sarcolemma, opening voltage-gated channels there.Again Na+ diffuses into the cell following its electrochemical gradient.

Repolarization: Restoring the sarcolemma to its initialpolarized state (negative inside, positive outside). Repolarizationoccurs as Na+ channels close (inactivate) and voltage-gated K+ channelsopen. Because K+ concentration is substantially higher inside the cellthan in the extracellular fluid, K+ diffuses rapidly out of the muscle fiber.

1

2

3

Closed Na+

channelOpen K+

channel

Na+

K+

−−−−−−−−−−−−−−−−−−−

−−−−

−−−−−−−− −−−−−−−−−−−−

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Figure 9.10 Action potential tracing indicates changes in Na+ and K+ ion channels.

Mem

bran

e po

tent

ial (

mV) +30

0

–95

0 5 10 15 20

Depolarizationdue to Na+ entry

Na+ channelsclose, K+ channelsopen

Repolarizationdue to K+ exit

K+ channelsclosed

Na+

channelsopen

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Excitation-Contraction (E-C) Coupling

• Events that transmit AP along sarcolemma lead to sliding of myofilaments

• AP brief; ends before contraction– Causes rise in intracellular Ca2+ which

contraction• Latent period

– Time when E-C coupling events occur– Time between AP initiation and beginning of

contraction

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Figure 9.11 Excitation-contraction (E-C) coupling is the sequence of events by which transmission of anaction potential along the sarcolemma leads to the sliding of myofilaments.

Slide 2

Setting the stageThe events at the neuromuscular junction (NMJ) set the stage for E-C coupling by providing excitation. Released acetylcholine binds to receptor proteins on the sarcolemma and triggers an action potential in a muscle fiber.

Synapticcleft

Axon terminal ofmotor neuron at NMJ

Action poten-tial is generated

Muscle fiber

T tubuleTerminal cisternof SR

Triad

One sarcomere

One myofibril

SarcolemmaACh

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Figure 9.11 Excitation-contraction (E-C) coupling is the sequence of events by which transmission of anaction potential along the sarcolemma leads to the sliding of myofilaments.

A&P Flix™: Excitation-contraction coupling.

PLAY

Slide 9

The action potential (AP) propagates along the sarcolemma and down theT tubules.

Calcium ions are released. Transmission of the AP along the T tubules of the triads causes the voltage-sensitive tubule proteins to change shape. This shape change opens the Ca2+ release channels in the terminal cisterns of the sarcoplasmic reticulum (SR), allowing Ca2+ to flow into the cytosol.

Steps in E-C Coupling:

Terminal cisternof SR

Ca2+

releasechannel

Voltage-sensitivetubule protein

T tubuleSarcolemma

Calcium binds to troponin and removes the blocking action of tropomyosin. When Ca2+ binds, troponin changes shape, exposing binding sites for myosin (active sites) on the thin filaments.

Contraction begins: Myosin binding to actin forms cross bridges and contraction (cross bridge cycling) begins. At this point, E-C coupling is over.

The aftermathWhen the muscle AP ceases, the voltage-sensitive tubule proteins return to their original shape, closing the Ca2+ release channels of the SR. Ca2+ levels in the sarcoplasm fall as Ca2+ is continually pumped back into the SR by active transport. Without Ca2+, the blocking action of tropomyosin is restored, myosin-actin interaction is inhibited, and relaxation occurs. Each time an AP arrives at the neuromuscular junction, the sequence of E-C coupling is repeated.

Myosincross bridge

Active sites exposed and ready for myosin binding

Myosin

Tropomyosinblocking active sites

Actin

Troponin

2

1

3

4

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Figure 9.11 Excitation-contraction (E-C) coupling is the sequence of events by which transmission of an action potential along the sarcolemma leads to the sliding of myofilaments.

Setting the stageThe events at the neuromuscular junction (NMJ) set the stage for E-C coupling by providing excitation. Released acetylcholine binds to receptor proteins on the sarcolemma and triggers an action potential in a muscle fiber.

Synapticcleft Axon terminal of

motor neuron at NMJ

Action potentialis generated

ACh

Muscle fiber

T tubuleTerminal cisternof SR

Triad

One sarcomere

One myofibril

Sarcolemma

The action potential (AP) propagates along the sarcolemma and down theT tubules.

Calcium ions are released. Transmission of the AP along the T tubules of the triads causes the voltage-sensitive tubule proteins to change shape. This shape change opens the Ca2+ release channels in the terminal cisterns of the sarcoplasmic reticulum (SR), allowing Ca2+ to flow into the cytosol.

Steps in E-C Coupling:

Terminal cisternof SR

Ca2+

releasechannel

Voltage-sensitivetubule protein

T tubuleSarcolemma 1

2

3

4

Calcium binds to troponin and removes the blocking action of tropomyosin. When Ca2+ binds, troponin changes shape, exposing binding sites for myosin (active sites) on the thin filaments.

Contraction begins: Myosin binding to actin forms cross bridges and contraction (cross bridge cycling) begins. At this point, E-C coupling is over.

The aftermathWhen the muscle AP ceases, the voltage-sensitive tubule proteins return to their original shape, closing the Ca2+ release channels of the SR. Ca2+ levels in the sarcoplasm fall as Ca2+ is continually pumped back into the SR by active transport. Without Ca2+, the blocking action of tropomyosin is restored, myosin-actin interaction is inhibited, and relaxation occurs. Each time an AP arrives at the neuromuscular junction, the sequence of E-C coupling is repeated.

Myosincross bridge

Active sites exposed and ready for myosin binding

Myosin

Tropomyosinblocking active sites

Actin

Troponin

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Cross Bridge Cycle

• Continues as long as Ca2+ signal and adequate ATP present

• Cross bridge formation—high-energy myosin head attaches to thin filament

• Working (power) stroke—myosin head pivots and pulls thin filament toward M line

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Cross Bridge Cycle

• Cross bridge detachment—ATP attaches to myosin head and cross bridge detaches

• "Cocking" of myosin head—energy from hydrolysis of ATP cocks myosin head into high-energy state

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Figure 9.12 The cross bridge cycle is the series of events during which myosin heads pull thin filamentstoward the center of the sarcomere.

Slide 6

A&P Flix™: The Cross Bridge Cycle

PLAY

Actin Ca2+ Thin filament

Myosincross bridge Thick

filament

Myosin

ATPhydrolysis

In the absence of ATP, myosin heads will not detach, causing rigor mortis.

*This cycle will continue as long as ATP is available and Ca2+ is bound to troponin.

Cross bridge formation. Energized myosin head attaches to an actin myofilament, forming a cross bridge.

Cocking of the myosin head. As ATP is hydrolyzed to ADP and Pi, the myosin head returns to its prestroke high-energy, or “cocked,” position. *

Cross bridge detachment. After ATP attaches to myosin, the link between myosin and actin weakens, and the myosin head detaches (the cross bridge “breaks”).

The power (working) stroke. ADP and Pi are released and the myosin head pivots and bends, changing to its bent low-energy state. As a result it pulls the actin filament toward the M line.

1

2

3

4

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Role of Calcium (Ca2+) in Contraction

• At low intracellular Ca2+ concentration?---

• At high intracellular Ca2+ concentration?---

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ATP is needed ……

• To re-establish RMP at sarcolemma and synaptic knob

• For detachment and “re-cocking” of myosin heads

• For sarcoplasmic reticulum to reabsorb Ca++ ( by ATP dependant calcium pump)

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Review Principles of Muscle Mechanics

• Contraction may/may not shorten muscle– Isometric contraction: no shortening; muscle

tension increases but does not exceed load – Isotonic contraction: muscle shortens

because muscle tension exceeds load• Force and duration of contraction vary in

response to stimuli of different frequencies and intensities

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What if??????

• Ach were not removed from synaptic cleft.• Little or no ATP could be produced• The CNS sends volleys of high frequency

impulses to various muscles