c h a p t e r 9 muscles and muscle physiology. mdufilho table 9.3 comparison of skeletal, cardiac,...
TRANSCRIPT
MDufilho
Special Characteristics of Muscle Tissue
• Excitability:
• Contractility:
• Extensibility:
• Elasticity:
6/24/2012 3
MDufilho
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"
6/24/2012 4
MDufilho
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 vessel
Perimysiumwrapping a fascicleEndomysium(between individualmuscle fibers)
Musclefiber
Perimysium
Fascicle
6/24/2012 5
MDufilho
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
6/24/2012 6
MDufilho
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
Myofibril
NucleusLight I band
Dark A band
6/24/2012 9
MDufilho
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
6/24/2012 10
MDufilho
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
6/24/2012 11
MDufilho
Striations
• H zone:
• M line:
• Z disc (line):
• Thick filaments:
• Thin filaments:
• Sarcomere:6/24/2012 12
MDufilho
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
6/24/2012 13
MDufilho
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 discThin (actin)filamentElastic (titin)filamentsThick(myosin)filament
6/24/2012 14
MDufilho
Longitudinal section of filaments within onesarcomere of a myofibril
Thick filament
Thin 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.
6/24/2012 15
MDufilho
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 disc
Mline
Sarcolemma
Triad:• T tubule• Terminal cisterns of the SR (2)
Tubules ofthe SRMyofibrils
Mitochondria
6/24/2012 16
MDufilho
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
6/24/2012 17
MDufilho
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
6/24/2012 18
MDufilho
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 Z
II A
Z Z
I IA6/24/2012 19
MDufilho
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 IP
6/24/2012 20
MDufilho
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 Z
II A
Z Z
I IA6/24/2012 21
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
6/24/2012 22
MDufilho
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 neuron
Fusing synaptic vesicles
Degraded AChACh
Acetylcho-linesterase
ACh
4
3
2
1
5
6
6/24/2012 23
MDufilho
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.
6/24/2012 24
MDufilho
Figure 9.9 Summary of events in the generation and propagation of an action potential in a skeletalmuscle fiber.
Slide 1Open Na+
channel
Na+
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+
−−−−−−−−−−−−−−−−−−−
−−−−
−−−−−−−− −−−−−−−−−−−−
6/24/2012 25
MDufilho
Figure 9.10 Action potential tracing indicates changes in Na+ and K+ ion channels.
Mem
bra
ne p
ote
nti
al (m
V) +30
0
–95
0 5 10 15 20
Depolarizationdue to Na+ entry
Na+ channelsclose, K+ channelsopen
Repolarizationdue to K+ exit
K+ channelsclosed
Na+
channelsopen
Time (ms)6/24/2012 26
MDufilho
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
6/24/2012 27
MDufilho
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
6/24/2012 28
MDufilho
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.
PLAYPLAY
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 tubule
Sarcolemma
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
6/24/2012 29
MDufilho
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 tubule
Terminal 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
6/24/2012 30
MDufilho
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
6/24/2012 31
MDufilho
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
6/24/2012 32
MDufilho
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
PLAYPLAY
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
6/24/2012 33
MDufilho
Role of Calcium (Ca2+) in Contraction
• At low intracellular Ca2+ concentration?-
-
-
• At high intracellular Ca2+ concentration?-
-
-
6/24/2012 34
6/24/2012 MDufilho 35
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)
MDufilho
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
6/24/2012 36