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Discussion topics
Introduction
Myocyte- structure, development
Muscle proteins
Sarcomere
Sarcotubular system
Excitation- contraction coupling
Molecular basis of muscle contraction
Summary
Muscle relaxation
Conclusion
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 Introduction
Human body contains over 400 skeletal muscles
40-50% of total body weight

Functions of skeletal muscle

Body movement (Locomotion)
Maintenance of posture
Respiration
Diaphragm and intercostal contractions
Communication (Verbal and Facial)
Constriction of organs and vessels
Peristalsis of intestinal tract
Vasoconstriction of b.v. and other structures (pupils)
Production of body heat (Thermogenesis)
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 Skeletal Muscle Characteristics

Most are attached by tendons to bones

Cells are multinucleate
Striated – have visible banding
Voluntary – subject to conscious control
Cells are surrounded and bundled by
connective tissue = great force, but tires
easily
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 Terms
Sarcolemma = Cell membrane
Sarcoplasm = Cytoplasm
Sarcoplasmic Reticulum =
Endoplasmic Reticulum
Sarcosomes = Mitochontria

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 Structure of skeletal muscle:
connective tissue covering
Epimysium
Surrounds entire muscle
Perimysium
Surrounds bundles of muscle fibers
Endomysium
Surrounds individual muscle fibers

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Skeletal muscle structure

Composed of muscle cells

(fibers), connective tissue,
blood vessels, nerves
Fibers are long, cylindrical, and
• multinucleated
Tend to be smaller diameter in
small muscles and larger in
large muscles. 1mm- 4 cm in
length

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 •Develop from myoblasts;
numbers remain constant
•Striated appearance
•Nuclei are peripherally
located

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Embryologic origin:

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 Muscle fiber anatomy
Sarcolemma - cell membrane
Surrounds the sarcoplasm (cytoplasm of fiber)
Contains many of the same organelles seen in other cells
An abundance of the oxygen-binding protein myoglobin
Punctuated by openings called the transverse tubules (T-tubules)
Narrow tubes that extend into the sarcoplasm at right angles to
the surface
Filled with extracellular fluid
Myofibrils -cylindrical structures within muscle fiber
Are bundles of protein filaments (=myofilaments)
Two types of myofilaments
1. Actin filaments (thin filaments)

2. Myosin filaments (thickfilaments)

– At each end of the fiber, myofibrils are anchored to the inner surface
of the sarcolemma
– When myofibril shortens, muscle shortens (contracts)
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 Muscle proteins
Contractile proteins
Actin- thin myofiliment
Myosin- thick filament
Regulatory proteins
Tropomyosin
Troponin
Attachment proteins
Titin, nebulin, alpha actinin, dystrophin

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Structure of Actin and Myosin

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Thin Filament: composed of 3major
proteins
1. F (fibrous) actin
2. Tropomyosin Actin (Thin)
3. Troponin
Two strands of fibrous (F) actin form Myofilaments
a double helix extending the length
of the myofilament; attached at
either end at sarcomere.
Composed of G actin monomers
each of which has a myosin-
binding site
Actin site can bind myosin during
muscle contraction.
Tropomyosin: an elongated protein
winds along the groove of the F actin
double helix.
Troponin is composed of three
subunits:
Tn-A : binds to actin
Tn-T :binds to tropomyosin,
Tn-C :binds to calcium ions.

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 Many elongated myosin molecules
shaped like golf clubs.
Single filament contains roughly 300
Myosin (Thick) myosin molecules
Molecule consists of two heavy myosin
molecules wound together to form a rod
Myofilament portion lying parallel to the myosin
myofilament and two heads that extend
laterally.
Myosin heads
1. Can bind to active sites on the actin
molecules to form cross-bridges.
(Actin binding site)
2. Attached to the rod portion by a
hinge region that can bend and
straighten during contraction.
3. Have ATPase activity: activity that
breaks down adenosine
triphosphate (ATP), releasing
energy. Part of the energy is used to
bend the hinge region of the myosin
molecule during contraction

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 Sarcomere - repeating functional unitsof
a myofibril
Sarcomeres: Z Disk About 10,000 sarcomeres per
myofibril, end to end

to Z Disk Each is about 2 µm long

Differences in size, density, and
distribution of thick and thin filaments
gives the muscle fiber a banded or striated
appearance.
A bands: a dark band; full length of thick
(myosin) filament
M line - protein to which myosins attach
H zone - thick but NO thin filaments
I bands: a light band; from Z disks to ends of
thick filaments
Thin but NO thick filaments
Extends from Aband of one sarcomere to A
band of the next sarcomere
Z disk: filamentous network of protein.
Serves as attachment for actin myofilaments
Titin filaments: elastic chains of amino
acids; keep thick and t hi n filaments i n
proper alignment

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 Sarcoplasmic Reticulum (SR)
SR is an elaborate, smooth endoplasmic
reticulum
runs longitudinally and surrounds each myofibril
Form chambers called terminal cisternae on either
side of the T-tubules
A single T-tubule and the 2 terminal cisternae
form a triad
SR stores Ca++ when muscle not contracting
When stimulated, calcium released into sarcoplasm
SR membrane has Ca++ pumps that function to pump
Ca++ out of the sarcoplasm back into the SR after
contraction
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 Sarcoplasmic Reticulum (SR)

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Muscular Contraction
The sliding filament model
Muscle shortening occurs due to the movement of the
actin filament over the myosin filament
Formation of cross-bridges between actin and myosin
filaments
Reduction in the distance between Z-lines of the
sarcomere

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Sliding Filament Theory
Rest – uncharged ATP cross-bridge complex
Excitation-coupling – charged ATP cross-bridge
complex, “turned on”
Contraction – actomyosin – ATP > ADP & Pi +
energy
Recharging – reload cross-bridge with ATP
Relaxation – cross-bridges “turned off”

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Sliding Filament Model of Contraction

Thin filaments slide past the thick ones so that the

actin and myosin filaments overlap to a greater degree
In the relaxed state, thin and thick filaments overlap
only slightly
Upon stimulation, myosin heads bind to actin and
sliding begins

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Cross-Bridge Formation in Muscle
Contraction

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 Myosin ATPase Cycle

ADP

Pi

From: Stryer 1988. Biochemistry. Freeman [Link] on:

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 EM Shows Different TM positions along the Actin Filament

Relaxed Ca-Activated Rigor Ca-Activated

X-bridge
From: Craig & Lehman.. 2001. J. Mol. Biol 311: 1027.
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Excitation-Contraction Coupling

Mechanism where an
action potential causes
muscle fiber
contraction
Involves
Sarcolemma
Transverse or T tubules
Terminal cisternae
Sarcoplasmic reticulum
Ca2+
Troponin

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Sources of ATP for Muscle
Contraction

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Energy Sources
ATP provides immediate energy for muscle
contractions from 3sources
Creatine phosphate
During resting conditions stores energy to synthesize ATP
Anaerobic respiration
Occurs in absence of oxygen and results in breakdown of
glucose to yield ATP and lactic acid
Aerobic respiration
Requires oxygen and breaks down glucose to produce
ATP, carbon dioxide and water
More efficient than anaerobic

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 Energy for Muscle Contraction
Direct phosphorylation
Muscle cells contain creatine
phosphate (CP)
CP is a high-energy
molecule
After ATP is depleted, ADP is
left
CP transfers energy to
ADP, to regenerate ATP
CP supplies are exhausted in
about 20 seconds
C11/p19y/2r0i11ght © 2003 PearsJipnmeEr dPuhycsaiotloigisnt , Inc. p u b l i sh i n g as BFeignujraem6i.1n0a Cummings Slide 63.924
 Energy for Muscle Contraction

Anaerobic glycolysis
Reaction that breaks
down glucose without
oxygen
Glucose is broken down
to pyruvic acid to
produce some ATP
Pyruvic acid is
converted to lactic acid
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 Energy for Muscle Contraction
Aerobic Respiration
Series of metabolic
pathways that occur in
the mitochondria
Glucose is broken down
to carbon dioxide and
water, releasing energy
This is a slower reaction
that requires continuous
oxygen

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amin Cummings Slide 64.21 5