muscle physiology. outline: skeletal muscle 1)somatic motor pathways 2)neuromuscular junction...
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Muscle Physiology
Outline: Skeletal Muscle
1) Somatic Motor pathways
2) Neuromuscular junction (synapse)
3) Excitation of muscle cells
4) Contraction of muscle cells
5) Neural modulation of excitation-contraction
6) Variation in Skeletal muscle physiology
7) Energy sources for contraction
8) Effects of fatigue and exercise
Somatic Motor PathwaysPrimary Motor Cortex
Brainstem
Skeletal Muscle
Direct Pathways:
Fine Motor ControlMuscle Tone
Indirect Pathways:
PosturePositioningCoordination
Direct Pathways:
Fine Motor ControlMuscle Tone
Indirect Pathways:
PosturePositioningCoordination
Many muscles receive input from both pathways
Cerebellum: Coordination of Motor Output
Vestibulocerebellar
Posture & Balance
Spinocerebellar
Simple Movements
Cerebrocerebellar
Complex movements
Motor Commands Sensory feedback from proprioreceptors(muscle spindle and golgi organ)
Primary Motor Cortex
Neuromuscular Junction
Chemical synapse between Motor Neurons and Muscle Cells
Neuromuscular junction: Physiology
1) Action potential from Motor Neuron
2) VG Ca2+ channels open
3) Ca2+ influx
4) Vesicles of ACh release to synaptic cleft
5) ACh binds to ligand-gated Na+ channels on Muscle membrane
6) Na+ influx
7) Depolarization of Muscle cell EXCITABLE MEMBRANE
2
1
3
5
4
7
6
Depolarization of Muscle Cell
Resting
Depolarization
Repolarization
Resting
Dep
olar
izat
ion R
epolarizationEverything about muscle cell action potentials is identical to neurons (All-or-none, etc)!
Exception: RMP = -85 mV
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
Muscle microanatomy
Bone
TendonMuscle
Muscle Fascicle Muscle Fiber
Myofibril
Myosin
Actin
Myofibrils contain the contractile mechanism of skeletal muscle
Functional organization of Myofibril:The Sacromere
MyosinActin
Sarcomere
Z-disk Z-diskCross-bridges
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
Sliding Filament Model: Generalizations
Actin & Myosin do not change length
Only Actin moves
Each Sacromere shortens VERY LITTLE
Relaxation is passive
How do sliding filaments result in whole muscle shortening and force?
Fascicle
Sacrolemna
Muscular Dystrophy = NO DYSTOPHIN!
Cross-Bridge Cycling : Mechanism of Sliding Filaments
MyosinActin
Sarcomere
Z-disk Z-disk
Cross-bridges
Actin: Activation
Tropomyosin TroponinActin
REST: active sites are not exposed
ACTIVATION: Ca2+ binds to Troponin Exposing active sites
Active Site
Where does Ca2+ come from?
Sarcoplasmic Reticulum
T-tubules
Sacrolemna
Muscle Fiber
Calcium initiates muscle contraction:Where does Ca2+ come from in Skeletal Muscle?
Sarcoplasmicreticulum
RyR
T-tubule
Ca2+ Stores
1
Myosin
Actin
DHP: VG-Ca2+
RyR = Ryanodine Receptor-channel DHP = Dihydropyridine Ca2+ channel
Sarcoplasmicreticulum
RyR
Ca2+ EFFLUX
Myosin
Actin
DHP: VG-Ca2+
RyR = Ryanodine Receptor-channel DHP = Dihydropyridine Ca2+ Receptors
Skeletal Muscle: Calcium Efflux from SR
Cross Bridge Cycling: What happens after Actin & Myosin Bind?
Muscle Cross Bridge Video
Cross-bridge Cycling: Striated & Smooth MuscleCross-bridge Cycling: Striated & Smooth Muscle
1 2 3 4 5
1) Cross-bridge Formation
Myosin head: loaded with potential energy
Myosin
Actin
Pi
ADP
Cross-bridge Cycling: Striated & Smooth Muscle
1 2 3 4 5
2) Power Stroke: Phosphate release
Stored Potential Energy is releasedMyosin
Pi
ADP
Actin SLIDES
Cross-bridge Cycling: Striated & Smooth Muscle
1 2 3 4 5
3) ADP dissociation
Myosin
Actin
ADP
Cross-bridge Cycling: Striated & Smooth Muscle
1 2 3 4 5
4) Rigor State
Myosin
Actin
Cross-bridge Cycling: Striated & Smooth Muscle
1 2 3 4 5
5) NEW ATP Binding: Myosin detaches
Myosin
Actin
ATP
Rigor Mortis
Myosin Cocking (between steps 5 & 1)1 2 3 4 5
ATP + H20 ADP + Pi + H+ + ENERGY
Hydrolysis by Myosin ATPase
Myosin Cocking
Once Cocked the Myosin head is loaded with POTENTIAL ENERGY
Muscle Contraction: Synthesis
1) Brain send AP down Motor pathways to Neuromuscular junction
2) Neuromuscular junction propagates AP to sarcolemna
3) AP on sacrolemna propagates down t-tubules into SR
4) SR releases Ca2+; Myosin & Actin bind
5) Cross-bridge cycling; Sliding Filaments
How muscles RELAX
Sarcoplasmic Reticulum
T-tubules
Sacrolemna
Muscle Fiber
1) Action Potential move along Sacrolemna
2) Action Potenial penetrates T-tubules & SR
3) VG Ca2+ in SR open, releasing Ca2+ onto Sarcomeres
4) Ca2+ binds to Troponin, exposing Actin’s active sites
5) Actin Binds to Myosin
1) Acetylcholine detaches from Na+ channels at Neuromuscular junction
2) Ca2+ is pumped (by Ca2+ ATPase pump!) back into Sacroplasmic Reticulum
Return to resting position : Titin
MyosinActin
Sarcomere
Z-disk Z-disk
Cross-bridges
http://www.fbs.leeds.ac.uk/research/contractility/titin.htm
TITIN
Muscle Contraction lead to FORCE
What do we know about MUSCLE FORCE?
Tension: how muscle develop force
Single MOTOR UNIT developing tension
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!
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
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
When action potentials come VERY RAPIDLY muscle fiber CANNOT relax
Unfused (Incomplete) Tetanus Fused (Complete) Tetanus
Summation & Tetanus allow Summation & Tetanus allow single motor unitssingle motor units to increase Tension (Force) to increase Tension (Force)
Motor Unit Recruitment
Different Motor Units can WORK TOGETHER to further increase force!
Tension varies with the starting length of the sacromere
Muscle Twitches
Variation in Muscle Fibers
TYPE 1
TYPE 2B
TYPE 2A
Fiber type is the same within a Motor Unit!!!!!!!!!!!!!!!!!!!!!!
WHITE MUSCLE
RED MUSCLE
WildType = normal rat TransGenic = rat with more Type I
TG rat has darker muscles due to more myoglobin, mitochondria
Myoglobin
Oxygen
Fiber types & Diameter underlie the trade-off between sprinting & marathon running in Humans
Maximum Running Distance
Max
imum
Run
ning
Spe
ed
100 m Dash olympian – Type 2B
Marathon olympian – Type 1
Energy Sources for Contraction1) ATP is needed to break cross-bridge2) ATP > ADP + P is needed to relax Myosin head3) P release from Myosin provides energy for Power stroke
Where does the ATP come from?Where does the ATP come from?
Aerobic RespirationAnaerobic RespirationCreatine
10 seconds10 seconds 3 minutes 3 minutes HoursHours