Molecular Basis of Skeletal
Muscle Contraction
Dr. Abdelrahman Mustafa
Department of Basic Medical Sciences
Division of Physiology
Faculty of Medicine
Almaarefa Colleges
Objectives
By the end of this lecture, you should be able to:
Understand the Molecular mechanism of skeletal
muscle contraction including:
 Role of calcium ions in excitation contraction
coupling
 Sliding Filament Theory of Contraction
 The role of T-tubule and sarcoplasmic
reticulum
 Regulation of Calcium efflux and influx from
the sarcoplasmic reticulum and into the
sarcoplasm
 Molecular rearrangement of Actin and Myosin
 Myosin-ATPase cycle and Rigor Mortis
phenomenon
Sliding Filament Mechanism
Cross-bridge interaction between actin and
myosin brings about muscle contraction by
means of the sliding filament mechanism.
• Sliding Filaments = Muscle Contraction
• The Basic Steps:
1- Message sent
2- Neurotransmitter
3- Depolarization
4- Calcium + Troponin = Actin Exposed
5- Actin + Myosin (Contraction)
Neuron  Muscle (Muscle Fiber)
• 1)Message sent
– Conscious decision to move
– Physiotherapy
• 2)Nervous System
– Neurotransmitter released (ACh, acetylcholine)
– ACh binds to sarcolemma of muscle fiber
– ACh initiates opening of sodium-potassium channels
3)Depolarization
– Binding of ACh to sodium-potassium channels
– Opening of channels + Movement of Na-K+ across
sarcolemma
Imbalance of charges  electrical current (action
potential)
The Neuromuscular Junction
4)Sarcoplasmic Reticulum  Calcium
• Action Potential releases Calcium:
– Ca+ released from membrane of sarcoplasmic reticulum
to sarcomere
– Ca+ binds with troponin C:
• Troponin-Tropomyosion conformation changes
• Troponin & Tropomyosin no longer cover Actin
• Actin is exposed
(5) Myosin  Actin
• Once the active site of actin are exposed, the
myosin heads(cross bridges) become attached to
them, thus allowing sliding of actin on the myosin
(the actin filaments move towards the center of
the myosin & shortening occurs)
• The heads of myosin when in contact with the
active sites
• ATPase that catalyze the splitting of ATP to
ADP + Pi + energy
• The energy liberated is consumed in
contraction which is an active process
Power Stroke
• Activated cross bridge bends toward center of
thick filament, “rowing” in thin filament to
which it is attached
– Sarcoplasmic reticulum releases Ca2+
– Myosin heads bind to actin
– Hydrolysis of ATP transfers energy to myosin head
Myosin heads (bends) toward center of sarcomere
(power stroke)
– ATP binds to myosin head and detaches it from
actin
The Sliding Filament Theory
 Myosin crossbridges (small “bridges” on the thick filaments that extend to the
thin filaments)
©Thompson Educational Publishing, Inc.
2003. All material is copyright protected. It
is illegal to copy any of this material.
This material may be used only in a course
of study in which Exercise Science: An
The Sliding Filament Theory
 Myosin crossbridges
 Attach, rotate, detach, and re-attach in rapid succession
©Thompson Educational Publishing, Inc. 2003. All material is copyright protected. It is illegal to copy any of this material.
This material may be used only in a course of study in which Exercise Science: An Introduction to Health and Physical
Education (Temertzoglou/Challen) is the required textbook.
The Sliding Filament Theory
 Myosin crossbridges
 Results in the sliding or overlap of the actin and myosin filaments
 Causes sarcomere to contract (muscle contraction)
©Thompson Educational Publishing, Inc. 2003. All material is copyright protected. It is illegal to copy any of this material.
This material may be used only in a course of study in which Exercise Science: An Introduction to Health and Physical
Education (Temertzoglou/Challen) is the required textbook.
(6) Relaxation
• Acetylcholinesterase breaks down ACh at
neuromuscular junction
• Muscle fiber action potential stops, there no more
release of Ca2+ from lateral sacs.
– Myosin detaches and moves away from Actin
– Troponin & Tropomyosin cover up Actin
– Ca+ moves back into Sarcoplasmic Reticulum
– Repolarization  Sarcolemma stable again
– ATP is required for myosin head to release from
actin and come back to resting state
Role of Calcium in Cross-Bridge
Formation
• Increase in Ca2+ starts filament sliding
• Decrease in Ca2+ turns off sliding process
• Thin filaments on each side of sarcomere slide
inward over stationary thick filaments toward
center of A band during contraction
• As thin filaments slide inward, they pull Z lines
closer together
• Sarcomere shortens
Role of Calcium in Cross-Bridge
Formation
• During relaxed state
Role of Calcium in Cross-Bridge
Formation
• Excited
Changes in Banding Pattern During Shortening
Contraction-Relaxation Steps Requiring ATP
• Splitting of ATP by myosin ATPase provides
energy for power stroke of cross bridge
• Binding of fresh molecule of ATP to myosin
lets bridge detach from actin filament at end
of power stroke so cycle can be repeated
• Active transport of Ca2+ back into sarcoplasmic
reticulum during relaxation depends on
energy derived from breakdown of ATP
Applied Aspect
• Rigor Mortis ?
– Stiffness that develops after deaths
– No ATP
– As ATP is required for myosin head to release from
actin and come back to resting state. Lack of ATP
will result in constant binding of acting and
myosin cross bridge resulting in stiff ness
– Begins within 12 hours and ends after 48 hours
– After 48 hours, muscle cells begin to autolyse
Relationship of an action potential to
resultant muscle twitch
(1-2) Depolarization of
Sarcolemma & Generation of
Action Potential
(3) Calcium Ions released
from Sarcoplasmic
Reticulum
(10) Everything moves back &
contraction done!
(4-6) Calcium binds to troponin, tropomyosin
moves, actin exposed
(9) Calcium removed by active transport
(7-8) Myosin attaches to actin, Myosin moves actin, ATP released
Q1
Beside the Conscious decision to move skeletal
muscle contract as response to
A)Physiotherapy
B)Tapping by clinical hummer
C) Administration of drugs
D)Intake large quantities of Ca2+
Q2
• The Neurotransmitter that released to
conduct the massage at neuromuscular
junction is :
A) Dopamin
B) Acetylcholine
C) Adrenaline
D) Noradrenaline
Q3
• Ca+ released from membrane of sarcoplasmic
reticulum to
A)Thick filment
B)Myofibril
C)Sarcolemma
D) Sarcomere
Q4
• When The heads of myosin contact with the
active sites of Actin
A)ATPase will catalyze the splitting of ATP to ADP
+ Pi + energy
B)Ca+2 will released from scroplasm
C)Tropomyosin will cover the actin binding site
D)The action potential will start