MUSCULAR SYSTEM

Lecture-2
 Sliding filament theory of muscle
• The contraction of a muscle cell occurs as the
thin filaments slide past the thick filaments
• During contraction, the sarcomere shortens and
the thin & thick filaments overlap
• Objectives (Goals):
1. To explore the molecular structure &
functional features of the thick & thin filament
2. To understand the sequence of events in a
single cross bridge cycle & multiple cycle
Sarcomere
 Sliding filament theory of muscle
• The sliding filament theory of how a s.muscle
contracts, involves the activity of five different
molecules plus calcium ions
• 1. Myosin
• 2. Actin
• 3. Tropomyosin
• 4. Troponin
• 5. ATP
• 6. Calcium ions
How each molecule functions?
 Thick filament
• Myosin molecules are bundled together to form
the thick filament (brown color)
• The shape of a myosin is similar to a golf stick
• The head called cross-bridge has the ability to
move back and forth
 Thick filament
• The flexing movement of the head provides the
‘power stroke’ for muscle contraction
• The linear tail portion allow vertical movement,
so that cross-bridge can bind to actin
• The cross-bridge has two binding sites - one for
ATP
 Thick filament
• The position of the cross-bridge without ATP is
low-energy conformation (shape)
• The binding of ATP, transfers energy to the
myosin cross-bridge as ATP is hydrolyzed to
ADP and Pi (inorganic phosphorus), this shape
of cross-bridge is high energy state
• The second binding site of the myosin cross-
bridge has a strong attraction for binding to actin
 Thin filament
• The thin filaments are composed of actin (A),
tropomyosin (B) and troponin (C)
• Two actin protein chains are twisted into a double
helical chain
• Each actin has many specific sites for binding of
myosin cross-bridge
 Thin filament
• The regulatory protein tropomyosin surrounds the
actin chain and in the resting stage of muscle, it
covers the binding sites & stops myosin cross-
bridge binding (B)
• Third molecule, troponin are attached along the
tropomyosin chain (C )
 Calcium ions
• After an action potential, Ca ions are released from
the terminal cisternae and bind to troponin (E)
• This causes a conformational change in the
tropomyosin-troponin complex, dragging (pulling)
the tropomyosin strand ‘off’the binding sites (B)
• The five molecules and Ca ions function together
in a coordinated manner to cause the thin filament
to slide past the thick filament
 Six steps of cross-bridge cycling
• The influx of Ca ions triggering the exposure of
binding sites on actin
 Six steps of cross-bridge cycling
• The binding of myosin to actin
• The power stroke of the cross-bridge that cause
the sliding of the thin filament
 Six steps of cross-bridge cycling
• The binding of ATP to the cross-bridge, which
results in the cross-bridge disconnecting from
actin
• The hydrolysis of ATP leads energizing the
cross bridge
• The transport of Ca ions back to sarcoplasmic
 Introduction
• The energy necessary for muscle contraction is
provided by ATP
• Because muscle stores a limited amount of ATP,
mechanisms must be present to synthesize new
ATP for continued muscle activity
• The objectives (Goals) are:
To understand the cellular process for ATP
synthesis
 Adenosine Tri Phosphate
(ATP)
ATP is composed of the adenine nucleotide with
three phosphate groups attached by two high
energy phosphate bonds
 ATP
• The potential (stored) energy in ATP is released
when the terminal high-energy phosphate bond is
broken by a hydrolytic enzyme
• The end products of hydrolysis of ATP are ADP and
P

ATP + H2O → ADP + Pi + energy

 ATP
• ADP is not discarded as waste, but used in the
resynthesize of ATP
• Requires synthetic enzyme to carry dehydration
to build new ATP
• ATP is the energy currency of the cell

ADP + Pi + energy → ATP + H2O

 ATP Synthesis
• When ATP are depleted, muscle cells use three
process to synthesize additional ATP
1. Hydrolysis of creatine phosphate
2. Glycolysis
3. The Krebs cycle (citric acid cycle)
• Creatine phosphate is the immediate source of
energy for rebuilding ATP
• Creatine phosphate transfers a phosphate to ADP
to form ATP and energy
• CP + ADP → ATP
 ATP Synthesis
• But the amount of creatine phosphate is limited
• Glucose is the source of energy for ATP synthesis
• Glucose is available from the blood
• Glucose is also available from glycogen stored in
the muscle cells
• Glucose is broken down by a metabolic pathway-
glycolysis to synthesize ATP (anaerobic pathway)
• More ATP is synthesized in the Kerbs cycle which
requires oxygen (aerobic pathway).
Thank you for your attention!