Muscles are comprised of muscle tissues which contain myofibrils made up of thick and thin filaments. Skeletal muscle fibers contain repeating units called sarcomeres made of myosin thick filaments and actin thin filaments. Neuromuscular junctions transmit signals from motor neurons to trigger calcium release and contraction via troponin-tropomyosin interactions exposing actin binding sites. The sliding filament model describes skeletal muscle shortening through myosin crossbridges pulling actin filaments toward the center.

1. Muscles

2. Muscles:
Muscles are a specialized body part that produces movement or
locomotion in body. The muscle is comprised (largely) of muscle tissues. A
muscle tissue is made up of muscle cells, which in turn, consist of several
myofibrils.

3. (squamous, columnar and cuboidal epithelial cells)
(skeletal muscle, smooth muscle and cardiac muscle)
(neurons and supporting cells)
(connective tissue proper, cartilage, bone and blood).

10. Structure
 Striated appearance: Distinct series of alternating light and dark bands
perpendicular to the long axis
 Due to its elongated shape and the presence of multiple nuclei, a skeletal muscle
cell is also referred to as a muscle fiber formed from mono-nucleated myoblasts
 Muscle fibers have diameters between 10 and 100 mm and lengths that may
extend up to 20 cm
 Regeneration: In case of damage, they undergo a repair process involving a
population of undifferentiated stem cells known as satellite cells
 The term muscle refers to a number of muscle fibers bound together by
connective tissue (figure 9.2)

13. Cont.
 Skeletal muscles are usually attached to bones by bundles of collagen fibers known as tendons
 The tendons may be long or short
 The striated pattern in skeletal (and cardiac) muscle results from the arrangement of two types of filaments referred to
as;
 Thick filaments and
 Thin filaments
 These filaments are part of cylindrical bundles called myofibrils , which are approximately 1 to 2 mm in diameter.
 Most of the cytoplasm of a fiber is filled with myofibrils, each extending from one end of the fiber to the other and linked
to the tendons at the ends of the fiber.
 One unit of this repeating pattern of thick and thin filaments is known as a sarcomere

14.  The molecular structure of thick and thin filaments
 The thick filaments are composed almost entirely of the protein myosin
 The myosin molecule is composed of two large polypeptide heavy chains and four smaller light
chains
 These polypeptides combine to form a molecule that consists of two globular heads (containing
heavy and light chains) and a long tail formed by the two intertwined heavy chains.
 Two globular heads extend out to the sides, forming cross-bridges , which make contact with the
thin filament and exert force during muscle contraction
 Each globular head contains two binding sites, one for attaching to the thin filament and one for
ATP

16.  The thin filaments (which are about half the diameter of the thick filaments) are
principally composed of the protein actin , as well as two other proteins— troponin
and tropomyosin —that play important roles in regulating contraction.
 An actin molecule is a globular protein composed of a single polypeptide (a
monomer) that polymerizes with other actin monomers to form a polymer made up
of two intertwined, helical chains. These chains make up the core of a thin
filament.
 Each actin molecule contains a binding site for myosin.

17. Skeletal muscle fibers have an elaborate system
of membranes that play important roles in the
activation of contraction
1. The sarcoplasmic reticulum forms a series of
sleevelike segments around each myofibril
At the end of each segment are two enlarged
regions, known as terminal cisternae or “lateral
sacs”
Ca+2 is stored in the terminal cisternae and is
released into the cytosol following membrane
excitation
2. A separate tubular structure, the transverse
tubule ( T-tubule ) , lies directly between—and is
intimately associated with—the terminal cisternae
of adjacent segments of the sarcoplasmic
reticulum or sarcolemma
Action potentials propagating along the
surface membrane also travel throughout the
interior of the muscle fiber by way of the T-
tubules

18. Molecular Mechanisms of Skeletal Muscle Contraction
 Contraction: Refers to activation of the force-generating sites within muscle fibers—the cross
bridges
 Relaxation: Mechanisms that generate force are turned off and tension declines
 Motor neurons: The neurons whose axons innervate skeletal muscle fibers are known as motor
neurons (or somatic efferent neurons), and their cell bodies are located in the brainstem and
the spinal cord
 Motor unit: A motor neuron plus the muscle fibers it innervates is called a motor unit
 Motor end plate: The region of the muscle fiber plasma membrane that lies directly under the
terminal portion of the axon is known as the motor end plate.
 Neuromuscular junction: The junction of an axon terminal with the motor end plate is known
as a neuromuscular junction
 end-plate potential (EPP): Producing a local depolarization of the motor end plate known as an
end-plate potential (EPP).

19. Membrane Excitation: The Neuromuscular Junction
 Branches of a motor neuron axon form neuromuscular junctions with
the muscle fibers in its motor unit. Each muscle fiber is innervated
by a branch from only one motor neuron
A. Acetylcholine released by an action potential in a motor neuron
binds to receptors on the motor end plate of the muscle membrane,
opening ion channels that allow the passage of sodium and
potassium ions, which depolarize the end-plate membrane
B. A single action potential in a motor neuron is sufficient to produce
an action potential in a skeletal muscle fiber.
C. Signaling at the neuromuscular junction can be disrupted by a
number of different toxins, drugs, and disease processes.

20.  Disruption of Neuromuscular Signaling
 There are many ways by which disease or drugs can modify events
at the neuromuscular junction
Curare, a deadly arrowhead poison used by indigenous peoples
of South America, binds strongly to nicotinic ACh receptors. It
does not open their ion channels.
Bacterium Clostridium botulinum, blocks the release of
acetylcholine from axon terminals lead to food poisoning (used
for clinical and cosmetic procedures, including;
The inhibition of overactive extraocular muscles,
Prevention of excessive sweat gland activity,
Treatment of migraine headaches,
Reduction of aging-related skin wrinkles)

21.  Neuromuscular transmission can also be blocked by inhibiting
acetylcholinesterase e.g., by organophosphates pesticides and nerve gas
(antidote for organophosphate and nerve gas exposure includes both
pralidoxime , which reactivates acetylcholinesterase, and atropine , the
muscarinic receptor antagonist)
 Drugs that block neuromuscular transmission
 succinylcholine acts as an agonist to the ACh receptors (depolarizing)
Rocuronium and vecuronium bind to nicotinic ACh receptors but does not
open their ion channels (non-depolarizing).

22. Excitation–Contraction Coupling
 Refers to the sequence of events by which an action potential in the plasma
membrane activates the force-generating mechanisms
 Action potential in a skeletal muscle fiber lasts 1 to 2 msec and resultant
mechanical activity following an action potential may last 100 msec or more.
 The electrical activity in plasma membrane increased cytosolic Ca 2+
concentration which further activate the contractile apparatus long after the
electrical activity in the membrane has ceased.

24.  Presence of Ca2+ in the cytoplasm initiate force generation by the thick and thin filaments?
 The thin filament components troponin and tropomyosin
1. Tropomyosin
 Rod-shaped molecule.
 Chains of tropomyosin molecules are arranged end to end along the actin thin filament.
 These tropomyosin molecules partially cover the myosin-binding site on each actin monomer,
thereby preventing the cross-bridges from making contact with actin.
 Each tropomyosin molecule is held in this blocking position by the smaller globular protein,
troponin.

25. 1. Troponin, which
 Interacts with both actin and tropomyosin
 composed of three subunits designated by the letters;
I (inhibitory),
T (tropomyosin binding) and
C (Ca2+-binding).
 One molecule of troponin binds to each molecule of tropomyosin and regulates
the access to myosin-binding sites on the actin monomers in contact with that
tropomyosin.
 This is the status of a resting muscle fiber; troponin and tropomyosin
cooperatively block the interaction of cross-bridges with the thin filament.

26.  When Ca2+ binds to specific binding sites on the Ca2+-binding
subunit of troponin. The binding of Ca2+ produces a change in the
shape of troponin, which relaxes its inhibitory grip and allows
tropomyosin to move away from the myosin-binding site on each
actin molecule
 Removal of Ca2+ from troponin reverses the process, turning off
contractile activity.
 In a resting muscle fiber, the concentration of free, ionized calcium
in the cytosol is very low.

27. Sliding-Filament Mechanism
 When a skeletal muscle fiber actively shortens, the thin filaments are
propelled toward the center of their sarcomere by movements of the
myosin cross-bridges that bind to actin

30. Hormones and neurotransmitters, which act on smooth muscles are:
1. Acetylcholine
2. Antidiuretic hormone (ADH)
3. Adrenaline
4. Angiotensin II, III and IV
5. Endothelin
6. Histamine
7. Noradrenaline
8. Oxytocin
9. Serotonin.
Other Humoral Factors
Humoral factors other than the hormones cause relaxation of smooth muscle fibers.
1. Lack of oxygen
2. Excess of carbon dioxide
3. Increase in hydrogen ion concentration
4. Adenosine
5. Lactic acid
6. Excess of potassium ion
7. Decrease in calcium ion
8. Nitric oxide (NO), the endothelium-derived relaxing factor (EDRF).

31. Mechanics of Single-Fiber Contraction
 Contraction refers to the turning on of the cross-bridge cycle. Whether there is an accompanying change in
muscle length depends upon the external forces acting on the muscle.
 Two types of contractions can occur following activation of a muscle fiber:
1. An isometric contraction in which the muscle generates tension but does not change length;
2. A contraction in which the muscle changes length while the load on the muscle remains constant is an
isotonic (constant tension) contraction
A. An isotonic contraction in which the muscle shortens (concentric), moving a load; and
B. A lengthening (eccentric) contraction in which the external load on the muscle causes the muscle to
lengthen during the period of contractile activity

32. Twitch Contractions
 The mechanical response of a muscle fiber to a single action potential is known as a twitch
 Following the action potential, there is an interval of a few milliseconds known as the
latent period before the tension in the muscle fiber begins to increase
 The time interval from the beginning of tension development at the end of the latent
period to the peak tension is the contraction time
 The characteristics of an isotonic twitch depend upon the magnitude of the load being
lifted,
1. the latent period is longer,
2. the velocity of shortening (distance shortened per unit of time) is slower,
3. the duration of the twitch is shorter, and
4. the distance shortened is less

33.  Increasing the frequency of action potentials in a muscle fiber
increases the mechanical response (tension or shortening) up to
the level of maximal tetanic tension.
 Maximum isometric tetanic tension is produced at the optimal
sarcomere length . Stretching a fiber beyond its optimal length
or decreasing the fiber length decreases the tension generated.
 The velocity of muscle fiber shortening decreases with increases
in load. Maximum velocity occurs at zero load.

34. Skeletal Muscle Energy Metabolism
 At the beginning of exercise, muscle glycogen is the major
fuel consumed. As the exercise proceeds, glucose and fatty
acids from the blood provide most of the fuel, and fatty
acids become progressively more important during
prolonged exercise. When the intensity of exercise exceeds
about 70% of maximum, glycolysis begins to contribute an
increasing fraction of the total ATP generated.

35. Muscle Fatigue
 Definition: When a skeletal muscle fiber is repeatedly stimulated, the tension
developed in fiber eventually decreases even though the stimulation continues
(Figure 9.23). This decline in muscle tension as a result of previous contractile
activity is known as muscle fatigue
 A variety of factors may contribute to muscle fatigue, including;
 A decrease in ATP concentration and
 Increases in the concentrations of ADP, Mg2+, H+, and oxygen free radicals.
 Individually and in combination, those changes have effects such as;
 Decreasing Ca2+ uptake and storage by the sarcoplasmic reticulum,
 Decreasing the sensitivity of the thin filaments to Ca2+, and
 Inhibiting the binding and power-stroke motion of the cross-bridges.

37. Types of Skeletal Muscle Fibers
 The types of skeletal muscle fibers can be distinguished by their
maximal shortening velocities and the predominate pathway they
use to form ATP: slow-oxidative, fast-oxidative glycolytic, and fast-
glycolytic fibers.
A.Differences in maximal shortening velocities are due to different
myosin with high or low ATPase activities, giving rise to fast and
slow fibers.
B.Fast-glycolytic fibers have a larger average diameter than
oxidative fibers and therefore produce greater tension, but they
also fatigue more rapidly.

38. Whole-Muscle Contraction
 The tension produced by whole-muscle contraction
depends on the amount of tension each fiber develops and
the number of active fibers in the muscle
 Muscles that produce delicate movements have a small
number of fibers per motor unit, whereas large powerful
muscles have much larger motor units.
 Fast-glycolytic motor units not only have large-diameter
fibers but also tend to have large numbers of fibers per
motor unit.

40. Control of Muscle Tension / Control of Shortening Velocity
 Increases in muscle tension are controlled primarily by increasing the number of
active motor units in a muscle, a process known as recruitment. Slow-oxidative
motor units are recruited first; then fast-oxidative-glycolytic motor units are
recruited; and finally, fast-glycolytic motor units are recruited only during very
strong contractions. Increasing motor-unit recruitment increases the velocity at
which a muscle will move a given load.

41. Muscle Adaptation to Exercise
Exercise can alter a muscle’s strength and
susceptibility to fatigue.
a. Long-duration, low-intensity exercise increases
a fiber’s capacity for ATP production by increasing
the number of mitochondria resulting in increased
endurance.
b. Short-duration, high-intensity exercise increases
fiber diameter as a result of increased synthesis of
actin and myosin, resulting in increased strength.

42. Lever Action of Muscles and Bones
Movement around a joint generally involves
groups of antagonistic muscles; some flex a
limb at the joint and others extend the limb.
The lever system of muscles and bones
generally requires muscle tension far greater
than the load in order to sustain a load in an
isometric contraction.

43. Skeletal Muscle Disorders
 Muscle Cramps: are involuntary tetanic contractions related to heavy exercise
and may be due to dehydration and electrolyte imbalances in the fluid
surrounding muscle and nerve fibers
 Hypo calcemic Tetany: Hypo calcemic tetany is the involuntary tetanic
contraction of skeletal muscles that occurs when the extracellular Ca2+
concentration decreases to about 40% of its normal value.
 Muscular Dystrophy: are commonly occurring genetic disorders that result
from defects of muscle-membrane stabilizing proteins such as dystrophin.
Muscles of individuals with Duchenne muscular dystrophy progressively
degenerate with use.
 Myasthenia Gravis: is an autoimmune disorder in which destruction of ACh
receptors of the motor end plate causes progressive loss of the ability to
activate skeletal muscles.