Muscle Physiology

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Muscle Physiology
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Outline Skeletal Muscle

• Somatic Motor pathways
• Neuromuscular junction (synapse)
• Excitation of muscle cells
• Contraction of muscle cells
• Neural modulation of excitation-contraction
• Variation in Skeletal muscle physiology
• Energy sources for contraction
• Effects of fatigue and exercise

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Somatic Motor Pathways
Primary Motor Cortex
Indirect Pathways Posture Positioning Coordinat
ion
Direct Pathways Fine Motor Control Muscle Tone
Brainstem
Skeletal Muscle
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Indirect Pathways Posture Positioning Coordinat
ion
Direct Pathways Fine Motor Control Muscle Tone
Many muscles receive input from both pathways
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Cerebellum Coordination of Motor Output
Spinocerebellar Simple Movements
Primary Motor Cortex
Cerebrocerebellar Complex movements
Vestibulocerebellar Posture Balance
Sensory feedback from proprioreceptors (muscle
spindle and golgi organ)
Motor Commands
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Neuromuscular Junction
Chemical synapse between Motor Neurons and Muscle
Cells
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Neuromuscular junction Physiology

• Action potential from Motor Neuron
• VG Ca2 channels open
• Ca2 influx
• Vesicles of ACh release to synaptic cleft
• ACh binds to ligand-gated Na channels on Muscle
  membrane
• Na influx
• Depolarization of Muscle cell EXCITABLE MEMBRANE

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Depolarization of Muscle Cell
Resting
Depolarization
Repolarization
Depolarization
Resting
Repolarization
Everything about muscle cell action potentials is
identical to neurons (All-or-none,
etc)! Exception RMP -85 mV
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So you have an excited muscle cell membrane

• Excitation of the muscle cell membrane leads to
  muscle cell contraction via a mechanism called
• Excitation-Contraction Coupling

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Muscle microanatomy
Muscle Fascicle
Muscle Fiber
Muscle
Tendon
Bone
Actin
Myofibril
Myofibrils contain the contractile mechanism of
skeletal muscle
Myosin
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Functional organization of MyofibrilThe
Sacromere
Sarcomere
Actin
Myosin
Cross-bridges
Z-disk
Z-disk
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Sliding Filament Model Contraction
Relaxed Muscle large gap between actins
Resting Position of Z-disc
Contraction gap between actins NARROWS
Maximal contraction NO gap between actins
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Sliding Filament Model Generalizations
Actin Myosin do not change length Only Actin
moves Each Sacromere shortens VERY
LITTLE Relaxation is passive
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How do sliding filaments result in whole muscle
shortening and force?
Muscular Dystrophy NO DYSTOPHIN!
Fascicle
Sacrolemna
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Cross-Bridge Cycling Mechanism of Sliding
Filaments
Sarcomere
Cross-bridges
Actin
Myosin
Z-disk
Z-disk
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Actin Activation
Active Site
Tropomyosin
Troponin
Actin
REST active sites are not exposed
ACTIVATION Ca2 binds to Troponin
Exposing active sites
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Where does Ca2 come from?
T-tubules
Sarcoplasmic Reticulum
Sacrolemna
Muscle Fiber
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Calcium initiates muscle contractionWhere does
Ca2 come from in Skeletal Muscle?
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RyR
T-tubule
Sarcoplasmicreticulum
Ca2 Stores
DHP VG-Ca2
Actin
Myosin
RyR Ryanodine Receptor-channel
DHP Dihydropyridine Ca2 channel
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Skeletal Muscle Calcium Efflux from SR
RyR
DHP VG-Ca2
Sarcoplasmicreticulum
Ca2 EFFLUX
Actin
Myosin
RyR Ryanodine Receptor-channel
DHP Dihydropyridine Ca2 Receptors
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Cross Bridge Cycling What happens after Actin
Myosin Bind?
Muscle Cross Bridge Video
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Cross-bridge Cycling Striated Smooth Muscle
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5
Actin
ADP

• Cross-bridge Formation
• Myosin head
• loaded with potential energy

Pi
Myosin
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Cross-bridge Cycling Striated Smooth Muscle
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Actin SLIDES
ADP
2) Power Stroke Phosphate release Stored
Potential Energy is released
Pi
Myosin
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Cross-bridge Cycling Striated Smooth Muscle
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5
Actin
3) ADP dissociation
ADP
Myosin
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Cross-bridge Cycling Striated Smooth Muscle
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4) Rigor State
Actin
Myosin
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Cross-bridge Cycling Striated Smooth Muscle
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5) NEW ATP Binding Myosin detaches
Actin
ATP
Rigor Mortis
Myosin
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Myosin Cocking (between steps 5 1)
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Hydrolysis by Myosin ATPase
ADP Pi H ENERGY
ATP H20
Myosin Cocking
Once Cocked the Myosin head is loaded with
POTENTIAL ENERGY
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Muscle Contraction Synthesis

• Brain send AP down Motor pathways to
  Neuromuscular junction
• Neuromuscular junction propagates AP to
  sarcolemna
• AP on sacrolemna propagates down t-tubules into
  SR
• SR releases Ca2 Myosin Actin bind
• Cross-bridge cycling Sliding Filaments

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How muscles RELAX
T-tubules

• Action Potential move along Sacrolemna
• Action Potenial penetrates T-tubules SR
• VG Ca2 in SR open, releasing Ca2 onto
  Sarcomeres
• Ca2 binds to Troponin, exposing Actins active
  sites
• Actin Binds to Myosin

Sarcoplasmic Reticulum
Sacrolemna
Muscle Fiber

• Acetylcholine detaches from Na channels at
  Neuromuscular junction
• Ca2 is pumped (by Ca2 ATPase pump!) back into
  Sacroplasmic Reticulum

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Return to resting position Titin
Sarcomere
Cross-bridges
Actin
Myosin
Z-disk
Z-disk
TITIN
http//www.fbs.leeds.ac.uk/research/contractility/
titin.htm
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• Muscle Contraction lead to FORCE
• What do we know about MUSCLE FORCE?

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Tension how muscle develop force
Single MOTOR UNIT developing tension
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Muscle twitch contraction of motor unit in
response to a single action potential
Stimulus applied
Stimulus applied
Stimulus applied
Muscle Twitches are All-or-None!
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Motor Unit a single motor neuron and all the
muscle fibers it innervates
Muscle force can be altered 1) WITHIN SINGLE
MOTOR UNITS 2) BETWEEN MULTIPLE MOTOR UNITS
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Summation Single Motor Unit
Stimulus applied
Stimulus applied
Muscle fiber was not able to relax so tension
increased
Summation occurs because Ca2 is still bound to
actin 2nd AP releases MORE Ca2 causing more
actin to be exposed to myosin heads
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When action potentials come VERY RAPIDLY muscle
fiber CANNOT relax
Unfused (Incomplete) Tetanus
Fused (Complete) Tetanus
Summation Tetanus allow single motor units to
increase Tension (Force)
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Motor Unit Recruitment
Different Motor Units can WORK TOGETHER to
further increase force!
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Tension varies with the starting length of the
sacromere
Muscle Twitches
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Variation in Muscle Fibers
RED MUSCLE
TYPE 1
WHITE MUSCLE
TYPE 2B TYPE 2A
Fiber type is the same within a Motor
Unit!!!!!!!!!!!!!!!!!!!!!!
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WildType normal rat
TransGenic rat with more Type I
TG rat has darker muscles due to more myoglobin,
mitochondria
Myoglobin
Oxygen
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Fiber types Diameter underlie the trade-off
between sprinting marathon running in Humans
100 m Dash olympian Type 2B
Maximum Running Speed
Maximum Running Distance
Marathon olympian Type 1
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Energy Sources for Contraction
1) ATP is needed to break cross-bridge 2) ATP gt
ADP P is needed to relax Myosin head 3) P
release from Myosin provides energy for Power
stroke
Where does the ATP come from?
Anaerobic Respiration
Creatine
Aerobic Respiration
10 seconds 3 minutes Hours