1. Muscle Physiology Dr. Mohammad Alqudah, Ph.D.
Department of Physiology and Biochemistry
School of Medicine , M2 5th floor

2. Outline 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

3. Muscle Function Movement Thermogenesis Protection Posture Maintenance
Depends on type of muscle tissue
Depends on location of muscle tissue
Thermogenesis
Protection
Posture Maintenance
Joint Stabilization
The primary action of a muscle is to contract means to activate the muscle because activation can produce force without actual shortening as you might hold something against gravity

4. Muscle Tissue Characteristics
All muscle tissues share basic characteristics
Excitability
Contractility
Elasticity
Extensibility
Excitability: capacity of muscle to respond to a stimulus
Contractility: ability of a muscle to shorten and generate pulling force
Extensibility: muscle can be stretched back to its original length
Elasticity: ability of muscle to recoil to original resting length after stretched

5. 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

6. Muscle Tissue Types
Skeletal
Cardiac
Smooth

7. Muscle Comparison Chart
Muscle Tissue
Special structures
Cell Shape
Striae
Nucleus
Control
Multi-nucleate & peripheral
Skeletal
Cylindrical
Yes
Voluntary
none
Cardiac
Cylindrical & branched
Uninucleate & central
Intercalated discs
Yes
Involuntary
May be single-unit or multi-unit
Uninucleate & central
Smooth
Fusiform No
Involuntary

8. Skeletal Muscle Functional Anatomy

9. Skeletal muscle Physiologic anatomy of skeletal muscle
Large, multinucleated and striated

10. Skeletal Muscle Fiber Internal Organization of Muscle Fibers
Banded appearance
The striations are arranged longitudinally into myofibrils
Internal Organization of Muscle Fibers
The sarcolemma
The cell membrane of a muscle fiber (cell)
Surrounds the sarcoplasm (cytoplasm of muscle fiber)
A change in transmembrane potential begins contractions
Transverse tubules (T tubules)
Transmit action potential through cell
Allow entire muscle fiber to contract simultaneously
Have same properties as sarcolemma
Myofibrils
Lengthwise subdivisions within muscle fiber
Made up of bundles of protein filaments (myofilaments)
Myofilaments are responsible for muscle contraction
Types of myofilaments:
thin filaments:
made of the protein actin
thick filaments:
made of the protein myosin
Sarcoplasmic reticulum (SR)
A membranous structure surrounding each myofibril
Helps transmit action potential to myofibril
Similar in structure to smooth endoplasmic reticulum
Forms chambers (terminal cisternae) attached to T tubules
Triad
Is formed by one T tubule and two terminal cisternae
Cisternae:
concentrate Ca2+ (via ion pumps)
release Ca2+ into sarcomeres to begin muscle contraction

11. Z line M Lines and Z Lines: M line: the center of the A band
A small section of a myofibril is illustrated here. Note the thick myosin filaments are arranged between overlapping actin filaments. *The two Z lines mark the boundary of a sarcomere. The sarcomere is the functional unit of a muscle cell .We will examine how sarcomeres function to help us better understand how muscles work. A striped or striated pattern within myofibrils:
alternating dark, thick filaments (A bands) and light, thin filaments (I bands)
M Lines and Z Lines:
M line:
the center of the A band
at midline of sarcomere
Z lines:
the centers of the I bands
at two ends of sarcomere
Zone of overlap:
the densest, darkest area on a light micrograph
where thick and thin filaments overlap
The H Band:
the area around the M line has thick filaments but no thin filaments

12. General mechanism of muscle contraction

13. Excitation –Contraction Coupling
Links action potential to contraction
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

14. Molecular mechanism of Muscle contraction
Sliding mechanism or walk along theory

15. Sarcomere (the functional unit of skeletal muscle)
Characteristics of Contractile proteins
Sarcomere (the functional unit of skeletal muscle)
Internal Organization of Muscle Fibers
Sarcomeres
The contractile units of muscle
Structural units of myofibrils
Form visible patterns within myofibrils
Muscle striations
A striped or striated pattern within myofibrils:
alternating dark, thick filaments (A bands) and light, thin filaments (I bands)
M Lines and Z Lines:
M line:
the center of the A band
at midline of sarcomere
Z lines:
the centers of the I bands
at two ends of sarcomere
Zone of overlap:
the densest, darkest area on a light micrograph
where thick and thin filaments overlap
The H Band:
the area around the M line has thick filaments but no thin filaments
Titin:
Strands of protein
reach from tips of thick filaments to the Z line
stabilize the filaments

16. 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

17. 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

18. Initiating Contraction
Ca2+ binds to receptor on troponin molecule
Troponin–tropomyosin complex changes
Exposes active site of F-actinThick Filaments
Contain twisted myosin subunits
Contain titin strands that recoil after stretching
The mysosin molecule
Tail:
binds to other myosin molecules
Head:
made of two globular protein subunits
reaches the nearest thin filament
Myosin Action
During contraction, myosin heads
Interact with actin filaments, forming cross-bridges
Pivot, producing motion
Skeletal Muscle Contraction
Sliding filament theory
Thin filaments of sarcomere slide toward M line, alongside thick filaments
The width of A zone stays the same
Z lines move closer together

19. 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

20. Sarcomere Contraction
Which filament has moved as the sarcomere contracted? Note the thick myosin filaments have not changed, but the thin actin filaments have moved closer together.

21. 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

22. The Ca ions bind to the troponin
This binding weakens troponin-tropomoysin complex and actin
Troponin moiecule changes position, rolling the tropomyosin away from the active sites on actin
Thus allowing them to interact with energized myosin heads

23. With the active sites on the actin exposed, the myosin heads bind to the, forming cross-bridges

24. Happens the muscles of the body after death
After cross-bridge formation, the ATP present in the myosin is used to “cock” (the opposite direction from its resting state). As the ATP is used and the ADP + P is released, the “power stroke” occurs as the myosin pivots toward the M line.
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

25. When another ATP molecule attaches to the myosin head, the cross-bridge between the active site of the actin molecule and myosin head is broken. Thus freeing up the head to make another bridge and complete the contraction.

26. Myosin splits the ATP into ADP + P and uses the released energy to re-cock the myosin head (reaching forward). Cycle can be repeated endlessly as along as calcium ion concentration remain high and sufficient ATP is present.
ATP produced in cells – aerobic vs. anaerobic
Ca controlled by what?

27. Watch the Cross Bridge Cycle animation.

28. 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)
Is the location of neural stimulation
Action potential (electrical signal)
Travels along nerve axon
Ends at synaptic terminal
Synaptic terminal:
releases neurotransmitter (acetylcholine or ACh)
into the synaptic cleft (gap between synaptic terminal and motor end plate)

29. 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:
Synthesis - in presynaptic terminals by the enzyme choline acetyltransferese
Storage – 10,000 to 20,000 Ach molecules per vesicle
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.

30. 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

31. Drugs that affect the transmission at the neuromuscular junction
Ach release :
Ca+2
Mg+ and Mn+
Botulin toxin
Bind to the receptors
D – tubocurare ( curare) inhibits transmission
Carbachole
Methacholine Ach like effect
Cholinesterase inhibitors:
Irreversible – nerve gas and insecticides
Reversible - neostigmine and physiostigmine

32. Myasthenia gravis: autoimmune disease where antibodies against the Ach receptors are produced. Which consequences do you expect?

33. Characteristics of muscle contraction
Single action potential (stimulation) causes single muscle contraction (Twitch)
Twitch three phases : Latent, contraction and relaxation

34. Figure 12.16

35. Recruitment (multiple motor unit summation)
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
Tension Produced by Whole Skeletal Muscles
Depends on
Internal tension produced by muscle fibers
External tension exerted by muscle fibers on elastic extracellular fibers
Total number of muscle fibers stimulated
Motor units in a skeletal muscle
Contain hundreds of muscle fibers
That contract at the same time
Controlled by a single motor neuron
Recruitment (multiple motor unit summation)
In a whole muscle or group of muscles, smooth motion and increasing tension are produced by slowly increasing the size or number of motor units stimulated
Maximum tension
Achieved when all motor units reach tetanus
Can be sustained only a very short time

36. 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

37. 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

38. 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.

39. Isometric/isotonic contractions
Isometric: muscle contraction without movement  no muscle shortening
Isotonic: muscle contraction with movement  muscle shortens

40. 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

41. 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
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

42. The velocity of muscle contraction varies inversely with the afterload
Concentric contraction – shortening of the muscle
Eccentric contraction lengthening