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SEMINAR
ON
SKELETAL MUSCLE TISSUE
ADDIS ABABA UNIVERSITY
FACULTY OF MEDICINE DEPARTMENT OF ANATOMY
December, 2023
Addis ababa, Ethiopia
By: Mankelklot Kasahun
Outline
• Overview of muscle tissue
• Skeletal muscle tissue
• Organization of SKM
• Organization within SKM fibers
• Actomyosin cross-bridg cycle
• Contraction
• Innervation
• Muscle spindle and tendon
• Types of skeletal muscle fibers
12/30/2023 2
Objectives
• By the end of this class, the student will be able to define the various
types of muscle tissue and describe their distinct roles in the body.
• Describe the characteristics of skeletal muscle tissue
• Describe the hierarchical organization of skeletal muscles
• Explain the the actomyosin cross bridg cycle
• Describe the mechanism of muscle contraction
• Define the innervation of skeletal muscles
• Define and distinguish between Type I and Type II skeletal muscle
fibers,
12/30/2023 3
OVERVIEW
• Derived from mesoderm
• Cells are called myofibrils (muscle cell, muscle fibers)
• Length>width
• Specialized for contraction
• Contain myofilaments: actin and myosin
• ATP hydrolysis provide the energy for contraction
12/30/2023 4
CLASSIFICATION OF
MUSCLE TISSUE
• Based on morphologic and functional characteristics
I. Skeletal muscle contains bundles of very long, multinucleated cells with
cross-striations.
• Their contraction is quick, forceful, and usually under voluntary control.
II. Cardiac muscle also has cross-striations and is composed of elongated,
often branched cells bound to one another at structures called
intercalated discs that are unique to cardiac muscle.
• Contraction is involuntary, vigorous, and rhythmic.
III. Smooth muscle consists of collections of fusiform cells that lack
striations and have slow, involuntary contractions.
12/30/2023 5
The three types of muscle.
12/30/2023 6
Cont’d
• according to the appearance of the contractile cells.
• Two principal types of muscle are recognized:
striated muscle, in which the cells exhibit crossstriations at the light
microscope level, and
smooth muscle, in which the cells do not exhibit crossstriations.
12/30/2023 7
Cont’d
• Striated muscle tissue is further subclassified on the basis of its
location:
• Skeletal muscle is attached to bone and is responsible for movement
of the axial and appendicular skeleton and for maintenance of body
position and posture.
In addition, skeletal muscles of the eye (extraocular muscles) provide
precise eye movement.
12/30/2023 8
Cont’d
• Visceral striated muscle is morphologically identical to skeletal
muscle but is restricted to the soft tissues, namely, the tongue,
pharynx, lumbar part of the diaphragm, and upper part of the
esophagus.
• These muscles play essential roles in speech, breathing, and
swallowing.
• Cardiac muscle is a type of striated muscle found in the wall of the
heart and in the base of the large veins that empty into the heart.
12/30/2023 9
Cont’d
• The cross-striations in striated muscle are produced largely by the
specific cytoarchitectural arrangement of both thin and thick
myofilaments.
• The two types of myofilaments occupy the bulk of the cytoplasm,
which in muscle cells is also called sarcoplasm
• The smooth ER is the sarcoplasmic reticulum, and the muscle cell
membrane and its external lamina are the sarcolemma.
12/30/2023 10
SKELETAL MUSCLE
• Consists of muscle fibers, which are long, cylindrical multinucleated
cells with diameters of 10-100 μm.
• A skeletal muscle cell is a multinucleated syncytium
• Straited muscle
• During embryonic muscle development, mesenchymal myoblasts fuse,
forming myotubes with many nuclei.
• Myotubes then further differentiate to form striated muscle fibers.
12/30/2023 11
Cont’d
Development of skeletal muscle
12/30/2023 12
Organization of a Skeletal Muscle
• A skeletal muscle consists of striated muscle fibers held together by
connective tissue.
• These connective tissue named according to their relationship with the
muscle fibers:
I. The epimysium, an external sheath of dense irregular connective
tissue, surrounds the entire muscle.
• Septa of this tissue extend inward, carrying the larger nerves, blood
vessels, and lymphatics of the muscle.
12/30/2023 13
Cont’d
II. The perimysium is a thin connective tissue layer that immediately
surrounds each bundle of muscle fibers termed a fascicle.
III. The endomysium, surrounds the external lamina of individual
muscle fibers.
12/30/2023 14
Organization of skeletal muscle
12/30/2023 15
Cont’d
• Collagens in these connective tissue layers of muscle serve to transmit
the mechanical forces generated by the contracting muscle cells/fibers.
• All three layers, plus the dense irregular connective tissue of the deep
fascia which overlies the epimysium, are continuous with the tough
connective tissue of a tendon at myotendinous junctions which join
the muscle to bone, skin, or another muscle.
• Ultrastructural studies show that in these transitional regions, collagen
fibers from the tendon insert themselves among muscle fibers and
associate directly with complex infoldings of sarcolemma.
12/30/2023 16
Cont’d
myotendinous junction
12/30/2023 17
Organization Within Muscle Fibers
• The organization within a muscle fiber is highly specialized and is
responsible for its contractile function.
1. Striated Appearance:
• Longitudinally sectioned skeletal muscle fibers exhibit a striated
appearance due to the arrangement of sarcomeres, the repeating
contractile units.
• The striations result from the alternating light and dark bands observed
under a microscope.
12/30/2023 18
Cont’d
Striated skeletal muscle in longitudinal
section.
12/30/2023 19
sarcomere
Cont’d
2. Myofilaments:
• Myofibrils consist of two main types of myofilaments: thick filaments
(composed of myosin) and thin filaments (primarily composed of
actin, troponin, and tropomyosin).
• The arrangement and interaction of thick and thin filaments during
muscle contraction form the basis of the sliding filament theory.
12/30/2023 20
12/30/2023 21
Cont’d
• Thick filament composed of protein called myosin.
• Several of these fibers wind around one another to circle one thick
filament.
• Toward the end of each thick filament are extension called myosin
heads
• It bind both actin, forming transient crossbridges between the thick
and thin filaments, and ATP, catalyzing energy release (actomyosin
ATPase activity).
12/30/2023 22
Cont’d
• The thin filament made up of globular protein called actin.
• These actin monomers combine to form a long polymer chain.
• Two of such actin polymer intertwine in helical fashion to form the
thin filament strand.
• Each G-actin monomer contains a binding site for myosin
• The thin filaments have two tightly associated regulatory proteins
Tropomyosin and Troponin,
12/30/2023 23
Cont’d
3. Sarcomeres:
• They are the structural and functional units of a muscle fiber.
• Contain overlapping thick and thin filaments, which give rise to the
characteristic striated pattern.
• They are delimited by Z-lines (Z-discs)
12/30/2023 24
12/30/2023 25
Structure of a myofibril: A series of sarcomeres.
Cont’d
• H-zone this the region of sarcomere that only contain the thick
filament
• NB: it does not include the entirety of thick filament
• I-band the region that only contain the thin filament
• NB: it extends over to sarcomere
• Z-line create bounderies of sarcomere.
• A-band these region contains all the thick filament in their entire
length
• NB: due to overlap, the A-band also include the small portion of thin
filament
12/30/2023 26
Cont’d
4. Myofibrils:
• They are long, cylindrical bundles running parallel to the long axis of
the fiber.
• They are composed of repeating sarcomeres and are responsible for
the muscle's striated appearance.
• They make up the majority of the muscle fiber's volume.
12/30/2023 27
12/30/2023 28
12/30/2023 29
Cont’d
5. Sarcoplasmic Reticulum (SR):
• Surrounding the myofibrils is the sarcoplasmic reticulum, a
specialized endoplasmic reticulum that stores and releases calcium
ions during muscle contraction.
6. T-Tubules:
• Are invaginations of the sarcolemma (muscle cell membrane) that
penetrate deep into the muscle fiber.
• They allow for the rapid transmission of signals from the surface to
the interior of the muscle fiber.
12/30/2023 30
Cont’d
7. Triad Structure:
• The combination of a T-tubule and two terminal cisternae of the
sarcoplasmic reticulum at each A-I band junction forms a triad.
• Triads are crucial for excitation-contraction coupling in muscle cells.
The organization within a muscle fiber is intricately designed to
facilitate the contraction and relaxation of the muscle.
12/30/2023 31
Organization of a skeletal muscle fiber
12/30/2023 32
The Actomyosin Cross-Bridge Cycle
• It is a series of molecular events that occur during muscle contraction.
• It involves the interaction between the contractile proteins actin and
myosin in the sarcomere of a muscle fiber.
• The coordinated activity of sarcomeres within myofibrils leads to the
contraction of muscle fibers and the generation of force for movement.
12/30/2023 33
Cont’d
• The cycle consists of several steps:
1. Beginning of the cross bridge cycle
• Myosin head strongly bound to the actin molecule
• ATP is absent
• Original/ unbent conformation
• Very short lived arrangement is known as rigor configuration
12/30/2023 34
Cont’d
2. ATP bounds to myosin head and induce conformational change in
the actin binding site
• This decrease the affinity and myosin head uncouple of thin filament
3. ATP binding site undergo further conformational change causing the
myosin head bend
• Pre-power stroke
• ATP breakdown
12/30/2023 35
Cont’d
4. Myosin head binds weakly to its new binding site on the actin
molecule of thin filament
5. Release of Pi has two effect
I. Binding affinity increase
II. Myosin head generate a force as it returns to its original unbent
position, thus as the myosin head straighten it forces movement of
the thin filament along thick filament. This is power stroke of cycle
• ADP is lost from myosin head
6. Again myosin head tightly bound to a new molecule of thin filament
12/30/2023 36
Cont’d
• The actomyosin cross-bridge cycle is fundamental to muscle
contraction, allowing the sliding of actin and myosin filaments,
resulting in the shortening of sarcomeres and, consequently, muscle
contraction.
• The regulation of this cycle is a key aspect of the control of muscle
contraction in response to neural signals and calcium concentration.
12/30/2023 37
12/30/2023 38
Actomyosin cross-bridge cycle.
Mechanism of Contraction
• Mechanism of muscle contraction involves dynamic interactions
between thick and thin filaments within sarcomeres.
• The actomyosin cross-bridge is the molecular event that drives this
sliding.
• The coordinated action of many sarcomeres contracting in unison
results in the observable contraction of the entire muscle fiber
• Notably, during contraction, neither thick nor thin filaments change
their length.
12/30/2023 39
Cont’d
 Initiation of Contraction:
• Contraction is induced by the arrival of an action potential at the
neuromuscular junction (NMJ).
• Action potential transmission along T-tubules to terminal cisternae
triggers the release of Ca2+ from the sarcoplasmic reticulum.
12/30/2023 40
Cont’d
 Regulation of Myosin-Actin Interaction:
• In a resting muscle, myosin heads cannot bind actin due to the
troponin-tropomyosin complex blocking binding sites on F-actin
filaments.
• Neural stimulation releases calcium ions that bind troponin, altering its
shape and moving tropomyosin to expose myosin-binding sites.
 Contraction Process:
• Binding actin induces a conformational change or pivot in the
myosins.
• Myosins pull thin filaments farther into the A band, toward the Z disc.
12/30/2023 41
Cont’d
 Energy Source:
• Energy for the myosin head pivot comes from the hydrolysis of ATP
bound to myosin heads.
• Myosin then binds another ATP, detaching from actin in a repeating
cycle.
 Repetition of Contraction Cycle:
• In the presence of Ca2+ and ATP, attach-pivot-detach events occur in a
rapid cycle, each lasting about 50 milliseconds.
• A single muscle contraction results from hundreds of these cycles.
12/30/2023 42
Diagrams and TEM micrographs show sarcomere
shortening during skeletal muscle contraction
12/30/2023 43
Diagrams and TEM micrographs show sarcomere
shortening during skeletal muscle contraction
12/30/2023 44
Cont’d
 Post-Contraction State:
• When neural impulses cease, and Ca2+ levels diminish, tropomyosin
covers myosin-binding sites, and filaments passively slide back.
• Sarcomeres return to their relaxed length.
 Rigor Mortis and Mitochondrial Activity:
• In the absence of ATP, actin-myosin crossbridges become stable.
• Rigidity in skeletal muscles (rigor mortis) occurs after death when
mitochondrial activity stops, and ATP is no longer produced.
12/30/2023 45
12/30/2023 46
1
2
3 4
5
• A nerve impulse triggers release
of ACh from the synaptic knob
into the synaptic cleft.
• ACh binds to ACh receptors in
the motor end plate of the
neuromuscular junction,
initiating a muscle impulse in
the sarcolemma of the muscle
fiber.
• calcium ions are released from
terminal cisternae into the
sarcoplasm.
• Calcium ions bind to troponin.
Troponin changes shape,
moving tropomyosin on the
actin to expose active sites on
actin molecules of thin
filaments. Myosin heads of
thick filaments attach to
exposed active sites to form
crossbridges
• Myosin heads pivot, moving thin
filaments toward the sarcomere
center. ATP binds myosin heads and is
broken down into ADP and P.
• Myosin heads detach from thin
filaments and return to their prepivot
position. The repeating cycle of
attach-pivot-detach-return slides thick
and thin filaments past one another.
The sarcomere shortens and the
muscle contracts.
• The cycle continues as long as
calcium ions remain bound to
troponin to keep active sites exposed.
When the impulse stops, calcium ions are actively
transported into the sarcoplasmic reticulum,
tropomyosin re-covers active sites, and filaments
passively slide back to their relaxed state.
Innervation
• Skeletal muscle fibers are richly
innervated by motor neurons that
originate in the spinal cord or
brainstem.
• The axons of the neurons branch as
they near the muscle, giving rise to
twigs or terminal branches that end
on individual muscle fibers
• Myelinated motor nerves branch
within the perimysium.
12/30/2023 47
Cont’d
• Formation of unmyelinated terminal
twigs that synapse with individual
muscle fibers.
• Schwann cells enclose axon branches,
and the external lamina fuses with the
sarcolemma.
• Axonal branches terminate within
troughs on the muscle cell surface,
forming NMJs or Motor End Plates
(MEP).
12/30/2023 48
Cont’d
• Axon terminals contain mitochondria and synaptic vesicles filled with
acetylcholine.
• The synaptic cleft between the axon and muscle, with deep junctional
folds on the sarcolemma, enhances signal transmission.
• When a nerve action potential reaches the MEP, acetylcholine is
released, diffuses across the cleft, and binds to receptors on the folded
sarcolemma.
12/30/2023 49
Cont’d
• Acetylcholine receptor opens a nonselective cation channel, leading to
cation influx and sarcolemma depolarization.
• Muscle action potential generation and the role of acetylcholinesterase
in removing free neurotransmitter.
12/30/2023 50
Cont’d
 Contraction Cycle and Motor Units
• Muscle action potential propagates along the sarcolemma and T-
tubules, reaching triads.
• Triads trigger Ca2+ release from the sarcoplasmic reticulum, initiating
the contraction cycle.
• A single motor neuron axon can form MEPs with one or many muscle
fibers, providing precise control.
12/30/2023 51
Muscle Spindles and Tendon Organs
• Striated muscles and myotendinous junctions house specialized
sensory receptors known as proprioceptors,
• These proprioceptors play a crucial role in providing the central
nervous system (CNS) with information from the musculoskeletal
system.
• There are several types of proprioceptors, including muscle spindles,
Golgi tendon organs, and joint receptors.
12/30/2023 52
Muscle Spindles
• specialized sensory organs located among muscle fascicles,
• Act as stretch detectors.
• encapsulated by modified perimysium.
• Comprise concentric layers of flattened cells, containing interstitial
fluid and thin muscle fibers (intrafusal fibers).
12/30/2023 53
Cont’d
• Sensory nerve axons penetrate and wrap around intrafusal fibers.
• Detect changes in length (distension) of surrounding muscle fibers
during body movements.
• Relay information to the spinal cord, mediating reflexes to maintain
posture and regulate opposing muscle groups in activities like walking.
12/30/2023 54
Golgi Tendon Organs
• Smaller encapsulated structures at the
myotendinous junction.
• Enclose sensory axons penetrating among
collagen bundles.
• Detect changes in tension within tendons
caused by muscle contraction.
• Inhibit motor nerve activity if tension
becomes excessive.
• Both muscle spindles and Golgi tendon
organs act as proprioceptors, helping
regulate the effort required for movements
with variable muscular force by detecting
increases in tension.
12/30/2023 55
Types of Skeletal Muscle Fiber
• Skeletal muscle fibers can be classified into different types based on
various characteristics, such as their contraction speed, resistance to
fatigue, and metabolic pathways.
• The two main types of skeletal muscle fibers are:
Type I (slow-twitch) and
Type II (fast-twitch).
• How skeletal muscle contracts??
12/30/2023 56
Cont’d
• SKM contract using contractile protein actin and myosin
• The head of myosin molecule have ATPase activity.
• They hydrolyse ATP in to ADP and energy used to bend the myosin
head at hinge region.
• Dragging the actin filament along with them inwards result in muscle
contraction.
12/30/2023 57
Cont’d
• If we put rate of force contraction and metabolic pathway together
then the muscle fibers will be classified as:
• Slow oxidative muscle fiber
• Fast glycolytic muscle fiber
• Fast oxidative glycolytic muscle fiber
12/30/2023 58
Major characteristics of skeletal muscle fiber types.
Slow, Oxidative
Fibers (Type I)
Fast, Oxidative-
Glycolytic
Fibers (Type IIa)
Fast, Glycolytic
Fibers (Type IIb)
Glycogen content Low Intermediate High
Major source of ATP
Oxidative
phosphorylation
Oxidative
phosphorylation
Anaerobic glycolysis
Glycolytic enzyme
activity
Low Intermediate High
Rate of fatigue Slow Intermediate Fast
Myosin-ATPase activity Low High High
Speed of contraction Slow Fast Fast
Typical major locations
Postural muscles of
back
Major muscles of legs Extraocular muscles
12/30/2023 59
Cont’d
Mitochondria Numerous Numerous Spars
Capillaries Numerous Numerous Sparse
Fiber diameter Small Intermediate Large
Size of motor unit Small Intermediate Large
Myoglobin content High (red fibers) High (red fibers) Low (white fibers)
12/30/2023 60
Cont’d
• Each muscle have these different fibers in different proportion
• The function of the muscle would determine which types of fiber
predominate
• Slow, oxidative fiber dominate in posture muscle the have to contract
for longer using lesser force and resistance to fatigue
• Ex. Marathon running
• Whereas muscle use on sprinting would have to contract for shorter
duration with more force and fatigue easier.
12/30/2023 61
References
12/30/2023 62
12/30/2023 63
Questions ??
12/30/2023 64
THANK YOU

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histology of skeletal muscle by mankelklot kasahun

  • 1. SEMINAR ON SKELETAL MUSCLE TISSUE ADDIS ABABA UNIVERSITY FACULTY OF MEDICINE DEPARTMENT OF ANATOMY December, 2023 Addis ababa, Ethiopia By: Mankelklot Kasahun
  • 2. Outline • Overview of muscle tissue • Skeletal muscle tissue • Organization of SKM • Organization within SKM fibers • Actomyosin cross-bridg cycle • Contraction • Innervation • Muscle spindle and tendon • Types of skeletal muscle fibers 12/30/2023 2
  • 3. Objectives • By the end of this class, the student will be able to define the various types of muscle tissue and describe their distinct roles in the body. • Describe the characteristics of skeletal muscle tissue • Describe the hierarchical organization of skeletal muscles • Explain the the actomyosin cross bridg cycle • Describe the mechanism of muscle contraction • Define the innervation of skeletal muscles • Define and distinguish between Type I and Type II skeletal muscle fibers, 12/30/2023 3
  • 4. OVERVIEW • Derived from mesoderm • Cells are called myofibrils (muscle cell, muscle fibers) • Length>width • Specialized for contraction • Contain myofilaments: actin and myosin • ATP hydrolysis provide the energy for contraction 12/30/2023 4
  • 5. CLASSIFICATION OF MUSCLE TISSUE • Based on morphologic and functional characteristics I. Skeletal muscle contains bundles of very long, multinucleated cells with cross-striations. • Their contraction is quick, forceful, and usually under voluntary control. II. Cardiac muscle also has cross-striations and is composed of elongated, often branched cells bound to one another at structures called intercalated discs that are unique to cardiac muscle. • Contraction is involuntary, vigorous, and rhythmic. III. Smooth muscle consists of collections of fusiform cells that lack striations and have slow, involuntary contractions. 12/30/2023 5
  • 6. The three types of muscle. 12/30/2023 6
  • 7. Cont’d • according to the appearance of the contractile cells. • Two principal types of muscle are recognized: striated muscle, in which the cells exhibit crossstriations at the light microscope level, and smooth muscle, in which the cells do not exhibit crossstriations. 12/30/2023 7
  • 8. Cont’d • Striated muscle tissue is further subclassified on the basis of its location: • Skeletal muscle is attached to bone and is responsible for movement of the axial and appendicular skeleton and for maintenance of body position and posture. In addition, skeletal muscles of the eye (extraocular muscles) provide precise eye movement. 12/30/2023 8
  • 9. Cont’d • Visceral striated muscle is morphologically identical to skeletal muscle but is restricted to the soft tissues, namely, the tongue, pharynx, lumbar part of the diaphragm, and upper part of the esophagus. • These muscles play essential roles in speech, breathing, and swallowing. • Cardiac muscle is a type of striated muscle found in the wall of the heart and in the base of the large veins that empty into the heart. 12/30/2023 9
  • 10. Cont’d • The cross-striations in striated muscle are produced largely by the specific cytoarchitectural arrangement of both thin and thick myofilaments. • The two types of myofilaments occupy the bulk of the cytoplasm, which in muscle cells is also called sarcoplasm • The smooth ER is the sarcoplasmic reticulum, and the muscle cell membrane and its external lamina are the sarcolemma. 12/30/2023 10
  • 11. SKELETAL MUSCLE • Consists of muscle fibers, which are long, cylindrical multinucleated cells with diameters of 10-100 μm. • A skeletal muscle cell is a multinucleated syncytium • Straited muscle • During embryonic muscle development, mesenchymal myoblasts fuse, forming myotubes with many nuclei. • Myotubes then further differentiate to form striated muscle fibers. 12/30/2023 11
  • 12. Cont’d Development of skeletal muscle 12/30/2023 12
  • 13. Organization of a Skeletal Muscle • A skeletal muscle consists of striated muscle fibers held together by connective tissue. • These connective tissue named according to their relationship with the muscle fibers: I. The epimysium, an external sheath of dense irregular connective tissue, surrounds the entire muscle. • Septa of this tissue extend inward, carrying the larger nerves, blood vessels, and lymphatics of the muscle. 12/30/2023 13
  • 14. Cont’d II. The perimysium is a thin connective tissue layer that immediately surrounds each bundle of muscle fibers termed a fascicle. III. The endomysium, surrounds the external lamina of individual muscle fibers. 12/30/2023 14
  • 15. Organization of skeletal muscle 12/30/2023 15
  • 16. Cont’d • Collagens in these connective tissue layers of muscle serve to transmit the mechanical forces generated by the contracting muscle cells/fibers. • All three layers, plus the dense irregular connective tissue of the deep fascia which overlies the epimysium, are continuous with the tough connective tissue of a tendon at myotendinous junctions which join the muscle to bone, skin, or another muscle. • Ultrastructural studies show that in these transitional regions, collagen fibers from the tendon insert themselves among muscle fibers and associate directly with complex infoldings of sarcolemma. 12/30/2023 16
  • 18. Organization Within Muscle Fibers • The organization within a muscle fiber is highly specialized and is responsible for its contractile function. 1. Striated Appearance: • Longitudinally sectioned skeletal muscle fibers exhibit a striated appearance due to the arrangement of sarcomeres, the repeating contractile units. • The striations result from the alternating light and dark bands observed under a microscope. 12/30/2023 18
  • 19. Cont’d Striated skeletal muscle in longitudinal section. 12/30/2023 19 sarcomere
  • 20. Cont’d 2. Myofilaments: • Myofibrils consist of two main types of myofilaments: thick filaments (composed of myosin) and thin filaments (primarily composed of actin, troponin, and tropomyosin). • The arrangement and interaction of thick and thin filaments during muscle contraction form the basis of the sliding filament theory. 12/30/2023 20
  • 22. Cont’d • Thick filament composed of protein called myosin. • Several of these fibers wind around one another to circle one thick filament. • Toward the end of each thick filament are extension called myosin heads • It bind both actin, forming transient crossbridges between the thick and thin filaments, and ATP, catalyzing energy release (actomyosin ATPase activity). 12/30/2023 22
  • 23. Cont’d • The thin filament made up of globular protein called actin. • These actin monomers combine to form a long polymer chain. • Two of such actin polymer intertwine in helical fashion to form the thin filament strand. • Each G-actin monomer contains a binding site for myosin • The thin filaments have two tightly associated regulatory proteins Tropomyosin and Troponin, 12/30/2023 23
  • 24. Cont’d 3. Sarcomeres: • They are the structural and functional units of a muscle fiber. • Contain overlapping thick and thin filaments, which give rise to the characteristic striated pattern. • They are delimited by Z-lines (Z-discs) 12/30/2023 24
  • 25. 12/30/2023 25 Structure of a myofibril: A series of sarcomeres.
  • 26. Cont’d • H-zone this the region of sarcomere that only contain the thick filament • NB: it does not include the entirety of thick filament • I-band the region that only contain the thin filament • NB: it extends over to sarcomere • Z-line create bounderies of sarcomere. • A-band these region contains all the thick filament in their entire length • NB: due to overlap, the A-band also include the small portion of thin filament 12/30/2023 26
  • 27. Cont’d 4. Myofibrils: • They are long, cylindrical bundles running parallel to the long axis of the fiber. • They are composed of repeating sarcomeres and are responsible for the muscle's striated appearance. • They make up the majority of the muscle fiber's volume. 12/30/2023 27
  • 30. Cont’d 5. Sarcoplasmic Reticulum (SR): • Surrounding the myofibrils is the sarcoplasmic reticulum, a specialized endoplasmic reticulum that stores and releases calcium ions during muscle contraction. 6. T-Tubules: • Are invaginations of the sarcolemma (muscle cell membrane) that penetrate deep into the muscle fiber. • They allow for the rapid transmission of signals from the surface to the interior of the muscle fiber. 12/30/2023 30
  • 31. Cont’d 7. Triad Structure: • The combination of a T-tubule and two terminal cisternae of the sarcoplasmic reticulum at each A-I band junction forms a triad. • Triads are crucial for excitation-contraction coupling in muscle cells. The organization within a muscle fiber is intricately designed to facilitate the contraction and relaxation of the muscle. 12/30/2023 31
  • 32. Organization of a skeletal muscle fiber 12/30/2023 32
  • 33. The Actomyosin Cross-Bridge Cycle • It is a series of molecular events that occur during muscle contraction. • It involves the interaction between the contractile proteins actin and myosin in the sarcomere of a muscle fiber. • The coordinated activity of sarcomeres within myofibrils leads to the contraction of muscle fibers and the generation of force for movement. 12/30/2023 33
  • 34. Cont’d • The cycle consists of several steps: 1. Beginning of the cross bridge cycle • Myosin head strongly bound to the actin molecule • ATP is absent • Original/ unbent conformation • Very short lived arrangement is known as rigor configuration 12/30/2023 34
  • 35. Cont’d 2. ATP bounds to myosin head and induce conformational change in the actin binding site • This decrease the affinity and myosin head uncouple of thin filament 3. ATP binding site undergo further conformational change causing the myosin head bend • Pre-power stroke • ATP breakdown 12/30/2023 35
  • 36. Cont’d 4. Myosin head binds weakly to its new binding site on the actin molecule of thin filament 5. Release of Pi has two effect I. Binding affinity increase II. Myosin head generate a force as it returns to its original unbent position, thus as the myosin head straighten it forces movement of the thin filament along thick filament. This is power stroke of cycle • ADP is lost from myosin head 6. Again myosin head tightly bound to a new molecule of thin filament 12/30/2023 36
  • 37. Cont’d • The actomyosin cross-bridge cycle is fundamental to muscle contraction, allowing the sliding of actin and myosin filaments, resulting in the shortening of sarcomeres and, consequently, muscle contraction. • The regulation of this cycle is a key aspect of the control of muscle contraction in response to neural signals and calcium concentration. 12/30/2023 37
  • 39. Mechanism of Contraction • Mechanism of muscle contraction involves dynamic interactions between thick and thin filaments within sarcomeres. • The actomyosin cross-bridge is the molecular event that drives this sliding. • The coordinated action of many sarcomeres contracting in unison results in the observable contraction of the entire muscle fiber • Notably, during contraction, neither thick nor thin filaments change their length. 12/30/2023 39
  • 40. Cont’d  Initiation of Contraction: • Contraction is induced by the arrival of an action potential at the neuromuscular junction (NMJ). • Action potential transmission along T-tubules to terminal cisternae triggers the release of Ca2+ from the sarcoplasmic reticulum. 12/30/2023 40
  • 41. Cont’d  Regulation of Myosin-Actin Interaction: • In a resting muscle, myosin heads cannot bind actin due to the troponin-tropomyosin complex blocking binding sites on F-actin filaments. • Neural stimulation releases calcium ions that bind troponin, altering its shape and moving tropomyosin to expose myosin-binding sites.  Contraction Process: • Binding actin induces a conformational change or pivot in the myosins. • Myosins pull thin filaments farther into the A band, toward the Z disc. 12/30/2023 41
  • 42. Cont’d  Energy Source: • Energy for the myosin head pivot comes from the hydrolysis of ATP bound to myosin heads. • Myosin then binds another ATP, detaching from actin in a repeating cycle.  Repetition of Contraction Cycle: • In the presence of Ca2+ and ATP, attach-pivot-detach events occur in a rapid cycle, each lasting about 50 milliseconds. • A single muscle contraction results from hundreds of these cycles. 12/30/2023 42
  • 43. Diagrams and TEM micrographs show sarcomere shortening during skeletal muscle contraction 12/30/2023 43
  • 44. Diagrams and TEM micrographs show sarcomere shortening during skeletal muscle contraction 12/30/2023 44
  • 45. Cont’d  Post-Contraction State: • When neural impulses cease, and Ca2+ levels diminish, tropomyosin covers myosin-binding sites, and filaments passively slide back. • Sarcomeres return to their relaxed length.  Rigor Mortis and Mitochondrial Activity: • In the absence of ATP, actin-myosin crossbridges become stable. • Rigidity in skeletal muscles (rigor mortis) occurs after death when mitochondrial activity stops, and ATP is no longer produced. 12/30/2023 45
  • 46. 12/30/2023 46 1 2 3 4 5 • A nerve impulse triggers release of ACh from the synaptic knob into the synaptic cleft. • ACh binds to ACh receptors in the motor end plate of the neuromuscular junction, initiating a muscle impulse in the sarcolemma of the muscle fiber. • calcium ions are released from terminal cisternae into the sarcoplasm. • Calcium ions bind to troponin. Troponin changes shape, moving tropomyosin on the actin to expose active sites on actin molecules of thin filaments. Myosin heads of thick filaments attach to exposed active sites to form crossbridges • Myosin heads pivot, moving thin filaments toward the sarcomere center. ATP binds myosin heads and is broken down into ADP and P. • Myosin heads detach from thin filaments and return to their prepivot position. The repeating cycle of attach-pivot-detach-return slides thick and thin filaments past one another. The sarcomere shortens and the muscle contracts. • The cycle continues as long as calcium ions remain bound to troponin to keep active sites exposed. When the impulse stops, calcium ions are actively transported into the sarcoplasmic reticulum, tropomyosin re-covers active sites, and filaments passively slide back to their relaxed state.
  • 47. Innervation • Skeletal muscle fibers are richly innervated by motor neurons that originate in the spinal cord or brainstem. • The axons of the neurons branch as they near the muscle, giving rise to twigs or terminal branches that end on individual muscle fibers • Myelinated motor nerves branch within the perimysium. 12/30/2023 47
  • 48. Cont’d • Formation of unmyelinated terminal twigs that synapse with individual muscle fibers. • Schwann cells enclose axon branches, and the external lamina fuses with the sarcolemma. • Axonal branches terminate within troughs on the muscle cell surface, forming NMJs or Motor End Plates (MEP). 12/30/2023 48
  • 49. Cont’d • Axon terminals contain mitochondria and synaptic vesicles filled with acetylcholine. • The synaptic cleft between the axon and muscle, with deep junctional folds on the sarcolemma, enhances signal transmission. • When a nerve action potential reaches the MEP, acetylcholine is released, diffuses across the cleft, and binds to receptors on the folded sarcolemma. 12/30/2023 49
  • 50. Cont’d • Acetylcholine receptor opens a nonselective cation channel, leading to cation influx and sarcolemma depolarization. • Muscle action potential generation and the role of acetylcholinesterase in removing free neurotransmitter. 12/30/2023 50
  • 51. Cont’d  Contraction Cycle and Motor Units • Muscle action potential propagates along the sarcolemma and T- tubules, reaching triads. • Triads trigger Ca2+ release from the sarcoplasmic reticulum, initiating the contraction cycle. • A single motor neuron axon can form MEPs with one or many muscle fibers, providing precise control. 12/30/2023 51
  • 52. Muscle Spindles and Tendon Organs • Striated muscles and myotendinous junctions house specialized sensory receptors known as proprioceptors, • These proprioceptors play a crucial role in providing the central nervous system (CNS) with information from the musculoskeletal system. • There are several types of proprioceptors, including muscle spindles, Golgi tendon organs, and joint receptors. 12/30/2023 52
  • 53. Muscle Spindles • specialized sensory organs located among muscle fascicles, • Act as stretch detectors. • encapsulated by modified perimysium. • Comprise concentric layers of flattened cells, containing interstitial fluid and thin muscle fibers (intrafusal fibers). 12/30/2023 53
  • 54. Cont’d • Sensory nerve axons penetrate and wrap around intrafusal fibers. • Detect changes in length (distension) of surrounding muscle fibers during body movements. • Relay information to the spinal cord, mediating reflexes to maintain posture and regulate opposing muscle groups in activities like walking. 12/30/2023 54
  • 55. Golgi Tendon Organs • Smaller encapsulated structures at the myotendinous junction. • Enclose sensory axons penetrating among collagen bundles. • Detect changes in tension within tendons caused by muscle contraction. • Inhibit motor nerve activity if tension becomes excessive. • Both muscle spindles and Golgi tendon organs act as proprioceptors, helping regulate the effort required for movements with variable muscular force by detecting increases in tension. 12/30/2023 55
  • 56. Types of Skeletal Muscle Fiber • Skeletal muscle fibers can be classified into different types based on various characteristics, such as their contraction speed, resistance to fatigue, and metabolic pathways. • The two main types of skeletal muscle fibers are: Type I (slow-twitch) and Type II (fast-twitch). • How skeletal muscle contracts?? 12/30/2023 56
  • 57. Cont’d • SKM contract using contractile protein actin and myosin • The head of myosin molecule have ATPase activity. • They hydrolyse ATP in to ADP and energy used to bend the myosin head at hinge region. • Dragging the actin filament along with them inwards result in muscle contraction. 12/30/2023 57
  • 58. Cont’d • If we put rate of force contraction and metabolic pathway together then the muscle fibers will be classified as: • Slow oxidative muscle fiber • Fast glycolytic muscle fiber • Fast oxidative glycolytic muscle fiber 12/30/2023 58
  • 59. Major characteristics of skeletal muscle fiber types. Slow, Oxidative Fibers (Type I) Fast, Oxidative- Glycolytic Fibers (Type IIa) Fast, Glycolytic Fibers (Type IIb) Glycogen content Low Intermediate High Major source of ATP Oxidative phosphorylation Oxidative phosphorylation Anaerobic glycolysis Glycolytic enzyme activity Low Intermediate High Rate of fatigue Slow Intermediate Fast Myosin-ATPase activity Low High High Speed of contraction Slow Fast Fast Typical major locations Postural muscles of back Major muscles of legs Extraocular muscles 12/30/2023 59
  • 60. Cont’d Mitochondria Numerous Numerous Spars Capillaries Numerous Numerous Sparse Fiber diameter Small Intermediate Large Size of motor unit Small Intermediate Large Myoglobin content High (red fibers) High (red fibers) Low (white fibers) 12/30/2023 60
  • 61. Cont’d • Each muscle have these different fibers in different proportion • The function of the muscle would determine which types of fiber predominate • Slow, oxidative fiber dominate in posture muscle the have to contract for longer using lesser force and resistance to fatigue • Ex. Marathon running • Whereas muscle use on sprinting would have to contract for shorter duration with more force and fatigue easier. 12/30/2023 61