1. The document discusses the structure and function of the neuromuscular junction and skeletal muscle contraction. It describes how an action potential causes the release of acetylcholine from the motor neuron, leading to depolarization of the muscle fiber membrane. 2. Calcium release within the muscle fiber initiates cross-bridge cycling between actin and myosin, producing muscle contraction. Contraction ceases as calcium is reabsorbed by the sarcoplasmic reticulum, relaxing the muscle. 3. The length-tension relationship states that skeletal muscle generates maximum force when sarcomeres are at their optimal resting length, with overlapping actin and myosin filaments. Shorter or longer lengths reduce the number of cross-

1. EXCITATION
CONTRACTION
COUPLING OF
SKELETAL
MUSCLEDr. Phiri S B

2. REVIEW OF THE SARCOMERE STRUCTURE
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3. MOTOR UNIT
•Def. A motor neuron and the muscle fibers it
innervates
• A muscle (whole muscle) can be innervated by several motor units
• Some muscles are innervated by one motor neuron
• Small motor units--Fine control
• small motor units contain as few as 3-6 muscle fibers per nerve fiber
• Example– eye muscle
• Large motor units--Strength control
• gastrocnemius muscle has 1000 fibers per nerve fiber
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4. NEUROMUSCULAR SRUCTURE
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5. • The neuromuscular junction is by definition a synapse
• Presynaptic motor axons are demyelinated and stop 30 nanometers from the
sarcolemma.
• This 30-nanometer space forms the synaptic cleft through which signalling molecules
are released.
• The sarcolemma has invaginations called postjunctional folds, which increase the
surface area of the membrane exposed to the synaptic cleft.
• These postjunctional folds form what is referred to as the motor endplate, which
possess acetylcholine receptors (AChRs) at a density of 10,000 receptors/micrometer
in skeletal muscle.
• The presynaptic axons form bulges called terminal boutons that project into the
postjunctional folds of the sarcolemma. Dr. Phiri S B

6. • The presynaptic boutons have active zones that contain vesicles, quanta, full of acetylcholine molecules.
• These vesicles can fuse with the presynaptic membrane and release ACh molecules into the synaptic
cleft via exocytosis after depolarization.
• AChRs are localized opposite the presynaptic terminals by protein scaffolds at the postjunctional folds of
the sarcolemma.
• Dystrophin, a structural protein, connects the sarcomere, sarcolemma, and extracellular matrix
components.
• Rapsyn is another protein that docks AChRs and structural proteins to the cytoskeleton.
• Also present is the receptor tyrosine kinase protein MuSK, a signaling protein involved in the
development of the neuromuscular junction, which is also held in place by rapsyn
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7. ACTIVITY OF NEUROMUSCULAR
JUNCTION
MUSCLE FIBER
MUSCLE IMPULSE
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9. NEUROMUSCULAR DESEASES
1.AUTOIMMUNE
a.Myasthenia gravis
b.Neonatal myasthenia gravis
c. Lambart-Eaton myasthenic syndrome
d.Neuromyotonia (Isaac’s syndrome)
2. GENETIC
a.Congenital myasthenic syndrome
b.Duchene muscular dystrophy
c. Bulbospinal muscular atrophy
(Kennedy’s syndrome)
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10. ACTIVITY OF NEUROMUSCULAR JUNCTION
• When an action potential in a motor neuron arrives at the axon
terminal,
• it depolarizes the nerve plasma membrane,
• opening voltage-sensitive calcium channels and allowing
calcium ions to diffuse into the axon terminal from the
extracellular fluid.
• This calcium binds to proteins that enable the membranes of
acetylcholine containing vesicles to fuse with the nerve plasma
membrane
• thereby releasing acetylcholine into the extracellular cleft
separating the axon terminal and the motor end plate.
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11. • ACh diffuses from the axon terminal to the motor end plate
• where it binds to receptors [of the nicotinic type].
• The binding of ACh opens an ion channel in each receptor
protein.
• Both sodium and potassium ions can pass through these
channels.
• Because of the differences in electrochemical gradients across
the plasma membrane,
• more sodium moves in than potassium out,
• producing a local depolarization of the motor end plate known as
an end-plate potential (EPP)
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12. GENERATION AND PROPAGATION OF
ACTION POTENTIAL IN THE SARCOLEMMA
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15. • There is sudden influx of sodium ions into the muscle fiber when the acetylcholine
channels open
• This causes the electrical potential inside the fiber at the local area of the end plate
to increase in the positive direction as much as 50 to 75 millivolts,
• Creating a local potential called the end plate potential.
• An increase in end plate membrane potential(EPP) initiate more and more opening of
sodium voltage sensitive channels, thus initiating an action potential at the muscle
fiber membrane (sarcolemma).
• Then the action potential sweep all around the sarcolemma and via the T-tubular
system
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16. • The conversion of this excitation into a contraction is called electromechanical coupling
• In the skeletal muscle, this process begins with the action potential exciting voltage sensitive
dihydropyridine receptors (DHPR) of the sarcolemma in the region of the triads.
• The DHPR are arranged in rows, and directly opposite them in the adjacent membrane of the
sarcoplasmic reticulum (SR) are rows of Ca2+ channels called ryanodine receptors (type 1 in
skeletal muscle: RYR1).
• Every other RYR1 is associated with a DHPR
• RYR1 open when they directly “sense” by mechanical means an AP-related conformational
change in the DHPR
• Then calcium is released from the sarcoplasmic reticulum in the sarcoplasm
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18. MECHANISM OF
CONTRACTION
1. Cross bridge formation
2. The power stroke
3. Cross bridge detachment
4. Reactivation of myosin head
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19. MECHANISM OF MUSCLE CONTRACTION & RELAXATION
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21. • In resting muscle, troponin I is bound to actin and tropomyosin and covers the sites
where myosin heads interact with actin.
• Also at rest, the myosin head contains tightly bound ADP.
• Following an action potential cytosolic Ca2+ is increased and free Ca2+ binds to
troponin C.
• This binding results in a weakening of the troponin I interaction with actin and exposes
the actin binding site for myosin to allow for formation of myosin/actin cross-bridges.
• Upon formation of the cross-bridge, ADP is released, causing a conformational change
in the myosin head that moves the thin filament relative to the thick filament,
comprising the cross- bridge “power stroke.”
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22. • ATP quickly binds to the free site on the myosin, which leads to a
detachment of the myosin head from the thin filament.
• ATP is hydrolyzed and inorganic phosphate (Pi) released, causing a “re-
cocking” of the myosin head and completing the cycle.
• As long as Ca2+ remains elevated and sufficient ATP is available, this
cycle repeats.
• Many myosin heads cycle at or near the same time, and they cycle
repeatedly, producing gross muscle contraction.
• Each power stroke shortens the sarcomere about 10 nm.
• Each thick filament has about 500 myosin heads, and each head cycles
about five times per second during a rapid contraction.
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23. SUMMARY OF CONTRACTION AND RELAXATION MECHANISMS
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DR BIG GIRB
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25. 1. Action potential is initiated and propagates in motor neuron axon.
2. Action potential triggers release of ACh from axon terminals at
neuromuscular junction.
3. ACh diffuses from axon terminals to motor end plate in muscle fiber.
4. ACh binds to receptors on motor end plate, opening Na, K ion channels.
5. More Na moves into the fiber at the motor end plate than K moves out,
depolarizing the membrane, producing the EPP.
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26. 6. Local currents depolarize the adjacent plasma membrane to its threshold potential,
generating an action potential that propagates over the muscle fiber surface and into the
fiber along the transverse tubules.
7. Action potential in transverse tubules triggers release of Ca2 from lateral sacs of
sarcoplasmic reticulum.
8. Ca2 binds to troponin on the thin filaments, causing tropomyosin to move away from
its blocking position, thereby uncovering cross-bridge binding sites on actin.
9. Energized myosin cross bridges on the thick filaments bind to actin
10. Cross-bridge binding triggers release of the strained conformational state of myosin,
producing an angular movement of each cross bridge
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27. 11. ATP binds to myosin, breaking linkage between actin and myosin and
thereby allowing cross bridges to dissociate from actin
12. ATP bound to myosin is split, energizing the myosin cross bridge
13. Cross bridges repeat steps 9 to 12, producing movement of thin filaments
past thick filaments. Cycles of cross-bridge movement continue as long as
Ca2 remains bound to troponin.
14. Cytosolic Ca2 concentration decreases as Ca2 is actively transported into
sarcoplasmic reticulum by Ca-ATPase.
15. Removal of Ca2 from troponin restores blocking action of tropomyosin, the
cross-bridge cycle ceases, and the muscle fiber relaxes
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28.  Contraction - when tension develop in a muscle as a result of
a stimulus
 Muscle “contraction” term may be confusing, because in some
contractions the muscle does not shorten in length
 As a result, it has become increasingly common to refer to the
various types of muscle contractions as muscle actions
instead

29.  Isometric contraction
◦tension is developed within muscle but joint
angles remain constant
◦static contractions
◦significant amount of tension may be
developed in muscle to maintain joint angle
in relatively static or stable position

30.  In isotonic contraction, the tension in the muscle remains
constant despite a change in muscle length.
 This can occur only when a muscle's maximal force of
contraction exceeds the total load on the muscle.
 Divided into concentric and eccentric contraction

31.  Concentric contraction
◦ muscle develops tension as it shortens
◦ occurs when muscle develops enough force to overcome applied
resistance
◦ causes movement against gravity or resistance
◦ described as being a positive contraction

32.  In eccentric contraction, the force generated is
insufficient to overcome the external load on the
muscle and the muscle fibers lengthen as they
contract.
 An eccentric contraction is used as a means of
decelerating a body part or object, or lowering a
load gently rather than letting it drop.

33.  Eccentric contraction (muscle action)
◦ Some refer to this as a muscle action instead of a
contraction since the muscle is lengthening as opposed to
shortening
 Various exercises may use any one or all of these contraction
types for muscle development

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36.  A resting muscle containing ATP can be stretched like a
rubber band
 A muscle’s resistance to stretch (Noncontractile component)
 series elastic components
 Tendons
 Parallel elastic components
Fascia (fibrous tissue)
epimysium,
perimysium,
Endomysium
giant filamentous elastic molecule called titin
(connectin)
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37.  The length of the muscle can be
varied by changing the distance
between its two attachments.
 At each length, the passive
tension is measured, the muscle
is then stimulated electrically,
and the total tension is
measured.
 The difference between the two
values at any length is the
amount of tension actually
generated by the contractile
process, the active tension.
 Plot passive tension and total
tension against muscle length.
 The length of the muscle at which
the active tension is maximal is
called its resting length
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38.  Strength of muscle contraction is a function of the number
of cross-links made between the actin and myosin chains
within the sarcomeres
 alterations in the proximity (length) of the actin and myosin
myofilaments affects the contraction force (tension) of a
muscle after stimulation
 maximum contractile force in the sarcomere occurs when
the full length of the actin strands at each end of the
sarcomere are in contact with the myosin molecule.
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39.  The total force of a muscle is the sum of its active
force and its extension force at rest.
 The active force is determined by the magnitude of
all potential actin-myosin interactions, which varies
in accordance with the initial sarcomere length.
 Resting length is the length to which a sarcomere is
stretched in a resting state.
 The effect of resting fiber length on muscular
contraction is referred to as the length-tension
relationship.
 Frank–Starling law stated that the “energy of contraction is
proportional to the initial length of the cardiac muscle fiber”
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40. 1. Skeletal muscle can develop maximum active (isometric) force
(F0) from its resting length (Lmax; sarcomere length = 2 to 2.2
μm).
2. When the sarcomeres shorten (L ‹ Lmax), part of the thin
filaments overlap, allowing only forces smaller than F0 to
develop.
3. When L is 70% of Lmax (sarcomere length: 1.65 μm), the thick
filaments make contact with the Z disks, and F becomes even
smaller.
4. a greatly pre-extended muscle (L›Lmax) can develop only
restricted force, because the number of potentially available
actin–myosin bridges is reduced.
5. When extended to 130% or more of the Lmax, the actin-myosin
interaction is completely lost and tension comes to zero.
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43. THANK YOU
Dr. Phiri S B