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Muscle Physiology
Dr. Mohammad Alqudah, Ph.D.
Department of Physiology and Biochemistry
School of Medicine , M2 5th floor
[email protected]
Outline
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Introduction and muscle functions
Skeletal Muscle Structure
Muscle Contraction: Cell Events
Muscle Contraction: Mechanical Events
Neuromuscular junction
Characteristics of muscle contraction
Muscle Metabolism
Types of Skeletal Muscle Fibers
Muscle Function
• Movement
– Depends on type of muscle tissue
– Depends on location of muscle tissue
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•
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Thermogenesis
Protection
Posture Maintenance
Joint Stabilization
Muscle Tissue Characteristics
All muscle tissues share basic characteristics
1.Excitability
2.Contractility
3.Elasticity
4.Extensibility
Classification of Muscle
- According to fine structure, neuronal control and anatomy
• Structurally, there are striated or smooth muscles
• Anatomically, Skeletal, cardiac and visceral muscles
• Neuronal control, voluntary and involuntary
Muscle Tissue Types
Skeletal
Cardiac
Smooth
Muscle Comparison Chart
Muscle
Tissue
Cell Shape
Striae
Nucleus
Control
Special
structures
Voluntary
none
Involuntary
Intercalated
discs
Involuntary
May be
single-unit or
multi-unit
Skeletal
Cylindrical
Yes
Multinucleate &
peripheral
Cardiac
Cylindrical &
branched
Yes
Uninucleate
& central
No
Uninucleate
& central
Smooth
Fusiform
Skeletal Muscle
Functional Anatomy
Skeletal muscle
Physiologic anatomy of skeletal muscle
Skeletal Muscle Fiber
Banded appearance
The striations are arranged longitudinally into myofibrils
Z line
Z line
General mechanism of muscle contraction
Excitation –Contraction Coupling
- Links action potential to contraction
1. Motor neuron excitation
- action potential in the nerve cell
- action potential in muscle cell
- the T tubule conducts the action
potential deep into the muscle
2. Ca+2 release from the SR into the
myoplasm…
The process by which depolarization of the T-tubule
Is converted to an intracellular calcium signal and the
Subsequent activation of contraction is called
Excitation-Contraction Coupling
Molecular mechanism of Muscle contraction
Sliding mechanism or walk along theory
http://highered.mcgrawhill.com/sites/0072495855/student_view0/cha
pter10/animation__sarcomere_contraction.ht
ml
Characteristics of Contractile proteins
Sarcomere
(the functional unit of
skeletal muscle)
The sarcomere
• The myofibrils are organized
into a repetitive pattern, the
sarcomere
• Myosin: thick filament
• Actin: thin filament
• Bands formed by pattern: A
and I and H bands
• Z line: area of attachment of
the actin fibers
• M line: Myosin fiber centers
Myosin Structure
• Myosin molecule consists of
6 proteins that make : tail,
hinge and heads (Two heavy
Chains and four light chains)
– Heads contain active sites for
• Actin
• ATP
• Titin a giant protein that serves as a
template for myosin assembly
• M Line
– stabilize the myosin filaments
– theorized to aid in transmission
of force from sarcomere to
cytoskeletal intermediate
filaments
M Line
Actin structure
• Thin filaments are
composed of
– g-actin molecules in
a helical arrangement
• Contain myosin binding
sites
– nebulin
• Filament that forms
internal support and
attachment for actin
– tropomyosin filaments
– troponin (complex of
three molecules)
attached to tropomyosin
• Has binding sites for
Ca2+
Figure 12.4
Sarcomere Contraction
Muscle Contraction: Mechanical Events
Acto-myosin cross bridge cycle
• Myosin heads bind to actin filaments
• ATP hydrolysis allows the myosin head to walk along the actin filament
• Myosin is an actin-activated AtPase
Rigor Mortis : In the absence of ATP, the muscles remain in a contraction state as the
myosin head stayed attached to actin ( ATP is the cause of separation) and this what
Happens the muscles of the body after death
Watch the Cross Bridge Cycle animation.
http://media.pearsoncmg.com/bc/bc_0media
_ap/apflix/ap/ap_video_player.html?cbc
Neuromuscular Junction
Components of neuromuscular junction
• Motor neuron
• End plate region
• Presynaptic terminal ( mitochondria and synaptic vesicles
10,000 Ach per vesicle)
• Synaptic cleft (or gap) (Cholinesterase)
• Postsynaptic membrane ( neurotransmitter’s receptors)
Mechanism of neuromuscular transmission
• Action potential is conducted from the motor neuron to the muscle chemically through
the neuromuscular junction via a substance called neurotransmitter like acetylcholine
• Events during transmission:
1. Synthesis - in presynaptic terminals by the enzyme choline acetyltransferese
2. Storage – 10,000 to 20,000 Ach molecules per vesicle
3. Release :
- Action potential arrives at terminal and causes depolarization and increases in calcium
influx to the terminal.
- Ca+2 in turn causes the vesicles to fuse with presynaptic membrane to empty its
content in the cleft.
- Ach diffuses across to the postsynaptic membrane where it activates its receptor .
- membrane conductance increases to Na + , results in depolarization called the end
plate potential( EPP), if the EPP exceeds threshold, action potential is produced and
muscle contracts.
Mechanism of neuromuscular transmission
4. Reuptake – Ach action in the cleft lasts only a short time because Ach is cleaved by the
action of cholinesterase , by products are reabsorbed and taken up by the presynaptic
terminal
End plate Potentials EPPs
• They are graded potentials with the amplitude depends upon amount of Ach
Drugs that affect the transmission at the neuromuscular junction
Ach release :
1. Ca+2
2. Mg+ and Mn+
3. Botulin toxin
Bind to the receptors
1. D – tubocurare ( curare) inhibits transmission
2. Carbachole
3. Methacholine
Ach like effect
Cholinesterase inhibitors:
1. Irreversible – nerve gas and insecticides
2. Reversible - neostigmine and physiostigmine
Myasthenia gravis: autoimmune disease where
antibodies against the Ach receptors are produced.
Which consequences do you expect?
Characteristics of muscle contraction
• Single action potential (stimulation) causes single muscle contraction (Twitch)
• Twitch three phases : Latent, contraction and relaxation
Figure 12.16
Muscle force depends on the number of motor units that are activated
• Stronger stimulus produces stronger twitch , as progressively increasing stimulus activates
More motor neurons , which activates more motor neurons which leads to more force.
(recruitment)
•
Motor unit is the motor neuron and all of its innervated muscle fibers
• The size principle : Motor units are recruited in order of their size
http://people.fmarion.edu/tbarbeau/physio_muscle_supplements.htm
Muscle force can be increased by increasing the frequency of motor
neuron firing
• The action potential is much shorter that the muscle twitch
• Thus, the nerve can stimulate the muscle before the muscle has relaxed or even before
it reaches its peak tension
• The frequency must exceed 1/twitch time (period) in order for summation to take place
• At high frequency the force shows no waviness, this is called Tetanus
Effect of consecutive stimuli: Treppe
• Treppe: gradual increase in
contraction intensity during
sequential stimulation
• Might be due to calcium ions
accumulating in the cytoplasm
with each stimulation
Figure 12.15
Molecular rational behind
frequency summation and
tantalization
• Single action potential causes single
Ca+2 transient.
• Force development depends on
intracellular Ca+2 concentration , so
repetitive stimulation causes
repetitive Ca+2 and hence more force.
Isometric/isotonic contractions
• Isometric: muscle
contraction without
movement  no
muscle shortening
• Isotonic: muscle
contraction with
movement  muscle
shortens
Muscle force depends on the length of the muscle
•
•
•
•
Stretching a muscle produces a passive force
The active tension rises and then falls with the stretch of the muscle
Active tension = Total tension - passive tension
The relationship between active force and muscle length is the Length-tension curve
The sliding filament hypothesis predicts that force depends on
the overlap of thick and thin filaments
• At a sarcomere length of 3.65u there is no force because there is no overlap.
• At progressively shorter length the overlap increases and the force increases as well
Until at 2.2 sarcomere length, there is maximal overlap and maximal force.
This force does not decrease until the sarcomere shortens to less that 1.95.
• At shorter length the thin filaments begin to run into each other and the number of
cross bridges decrease .
• When the thick filaments butt up against the Z-disk the force falls precipitously.
Figure 12.18
The velocity of muscle contraction varies inversely with the afterload
• Concentric contraction – shortening of the muscle
• Eccentric contraction lengthening