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The Muscular System
© 2007 McGraw-Hill Higher Education. All rights reserved.
Introduction
© 2007 McGraw-Hill Higher Education. All rights reserved.
Skeletal muscle anatomy
• Muscle
– Made up of fascicles (a bundle of muscle fibers)
– Fiber (muscle cell or myocyte)
• Made up of myofibrils
– Contain sarcomeres (functional unit)
» Myofilaments (actin and myosin)
– Connective tissue
• Epimysium
– Surrounds entire muscle
• Perimysium
– Surrounds fascicles
• Sarcolemma
– Surrounds fibers
• Satellite cells
– Allow muscle to adapt to activity
© 2007 McGraw-Hill Higher Education. All rights reserved.
Skeletal muscle anatomy
• Skeletal muscle cells are
multi-nucleated
– Unusual
• Satellite cells
– Myoblasts
• Essential for growth of
fibers
• Chemotaxic
– Can migrate around
cell
© 2007 McGraw-Hill Higher Education. All rights reserved.
Myotendinous junction
• Connection of muscle
to tendon
– Allow transmission
of force to bones
– Tendon
• connects to
bone
– Myotendinous
junction
• Common spot
for sports
injuries
© 2007 McGraw-Hill Higher Education. All rights reserved.
Sarcomeres
• Striated (striped)
appearance
• A band
– Anisotropic
• I band
– Isotropic
• Means having the
same optical
properties in all
directions
• H zone
– Light
• Z line
– Separates
sarcomeres
© 2007 McGraw-Hill Higher Education. All rights reserved.
Contractile and regulatory proteins
• Muscle
– ~75% water
– 20% protein
– 5% salts, pigments
and substrates
• Protein
– 12%
• myofibrillar
– 8%
• Enzymes,
membrane
proteins,
transport
channels
© 2007 McGraw-Hill Higher Education. All rights reserved.
Contractile proteins
• Major myofibrillar
proteins
– Actin and myosin
• Major contractile
proteins
• Myosin
– ATPase
– “head”
attaches to
actin
– Ratchet like
action
shortens
sarcomere
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– Troponin and tropomyosin
• On actin
• Ca2+ binds to troponin
• Causes conformational
change in tropomyosin
– Titin and nebulin
• Titin
– Connects myosin to
Z disc
• Nebulin
– Actin binding
protein; may limit
length
– M-line proteins
• Keep actin and myosin
in correct spatial
arrangement
– Desmin
• Links Z-disks together
– α-actinin
• Attaches actin filaments
ar Z disc
– Spectrin and dystrophin
• Dystrophin involved in
muscular dystrophy
© 2007 McGraw-Hill Higher Education. All rights reserved.
Contractile proteins
• Thick filament
– Hexameric protein
• One pair of heavy
chains (MHC)
• Two pairs of light
chains (LC)
• Muscle often
characterized by
MHC
– Type I
– Type II
» a, dx, b
• Light chains
– Modulate the
contractile
response
© 2007 McGraw-Hill Higher Education. All rights reserved.
Muscle organization
• Myosin
– Light meromyosin
• Links all myosin
molecules
together
– Heavy meromyosin
• Hinge and head
• Head interacts
with actin when
ATP is present
– ATPase
• Close to actin
binding site in
head region
© 2007 McGraw-Hill Higher Education. All rights reserved.
Muscle organization
• Actin
– Made up of G (globular)
actin sub-units
– (F) Filamentous actin
• String of G actin
– Tropomyosin (Tm)
• Filament that lies in
groove of actin
molecule
• Blocks myosin
binding site
– Troponin
• On G actin
• Ca2+ binding allows
myosin and actin to
interact
© 2007 McGraw-Hill Higher Education. All rights reserved.
Sliding filament theory
• Huxley and Huxley
1954
• Determined that the
following steps occur
– Myosin and actin
interact
– ATP hydrolyzed
– Cross bridge stroke
– Detachment of
myosin and actin
© 2007 McGraw-Hill Higher Education. All rights reserved.
Sliding filament theory
• A) no interaction
– ATP is hydrolyzed to
“energize” myosin
– Ca2+ release
– Myosin attaches to
actin
• B) crossbridge
movement
– ADP and Pi released
• C) ATP binds
– Breaks bond betw
actin and myosin
• D) ATP hydrolyzed to
“re-energize” myosin
© 2007 McGraw-Hill Higher Education. All rights reserved.
Capillaries and the microvascular unit
• Capillarity
– Several measures
• No. per fiber
– ~2-4 caps/fiber
– Problems?
• # Caps/fiber area
– ~500-1000
caps/mm2
– Problems?
• Cap length/fiber vol
– Best because
» Capillaries are
not straight
» Matches the
length of the
capillary to the
fiber volume
© 2007 McGraw-Hill Higher Education. All rights reserved.
© 2007 McGraw-Hill Higher Education. All rights reserved.
Microvascular unit
• Notice how tortuous or “non-straight” the
capillaries are in these corrosion casts
© 2007 McGraw-Hill Higher Education. All rights reserved.
Length-tension relationships
• The force or tension that
a muscle can exert is
dependent upon it’s
length
– Actually, the
sarcomere length
– Sarcomer has an
“optimal length”
• This is where
maximal actinmyosin overlap
occurs
© 2007 McGraw-Hill Higher Education. All rights reserved.
Types of contraction
• Isometric
– Generates force, but no
movement
• Isotonic
– Generates force and
shortening occurs
• Note: distance shortened is less
as load increases
• However, note how training
changes the force-velocity
relationship
– Specifically, a trained
muscle can
• Move a given load faster
• Move a greater load at
the same speed
compared to untrained
© 2007 McGraw-Hill Higher Education. All rights reserved.
Excitability
• Muscles exhibit the
property of excitability
– They can be
activated by a
nervous impulse
– They are polarized
(i.e. charged)
• Resting membrane
potential
– Inside negative
relative to outside
© 2007 McGraw-Hill Higher Education. All rights reserved.
Resting membrane potential
• Greater # of
negatively charged
particles (ions) inside
cell
– Most are proteins
– Also Na+, K+ and
Cl– Greater
extracellular Na+
and intracellular K+
– Resting membrane
potential is ~ -70
mV
• Na+/K+ ion
pump
• Membrane is
more permeable
+ than Na+
to
K
© 2007 McGraw-Hill Higher Education. All rights reserved.
Action potential
• When cell is stimulated
– Stimulus is subthreshold if there is no response
– If threshold is reached, action potential
• Action potential
– Rapid (1 ms) reversal of polarity
© 2007 McGraw-Hill Higher Education. All rights reserved.
Action potential
• Note that each ion has
it’s own equilibrium
potential (where
resting pot would be if
only that ion existed)
• Note how action
potential must be
strong enough to
reach threshold
• Also, Na+ influx is
responsible for AP
• K+ efflux is responsible
for repolarization
• Following AP,
membrane is
transiently more
negative,
hyperpolarization
© 2007 McGraw-Hill Higher Education. All rights reserved.
Neuroanatomy made ridiculously
simple
• Motor neuron
– Cell body
– Dendrites
– Axon
• Myelin sheaths
–Insulation
–Increases the rate
of nerve
transmission
• Nodes of Ranvier
• Motor end plate
–ACh
© 2007 McGraw-Hill Higher Education. All rights reserved.
Neuromuscular junction
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NMJ
• Connection between nervous system and muscular
system
– Branch from a motor neuron and the fiber it
innervates
– Small space (synapse)
• Ach is released from motor terminal or Motor
end plate
–Ach is contained in vesicles
–When action potential is reached
»Ca2+ enters the Motor end plate
»Causes Ach to be released
© 2007 McGraw-Hill Higher Education. All rights reserved.
AP transmission to muscle cell
• AP then transmitted
through the T-tubules
and sarcoplasmic
reticulum
– AP travels through Tsystem
– Calcium released from
Terminal citernae of
SR
– This caused
contraction
– Excitation-contraction
coupling
© 2007 McGraw-Hill Higher Education. All rights reserved.
Excitation contraction coupling
• AP propagated across
NMJ
– Down T-tubules
– Stimulates Ca2+ release
from SR
• Ryanodine receptor
– Ca2+ release
channel
– Ca2+ binds to troponin
– Causes shift in
tropomyosin
– Allows actin-myosin
interaction
– Contraction
• Cessation of AP
– Ca2+ resequestered
© 2007 McGraw-Hill Higher Education. All rights reserved.
Muscle fiber typing
• Stain for ATPase
– Different ATPases in
• Slow twitch
• Fast twitch
– Incubate muscle samples at different
pH
• Alkaline pH (10.3)
– Dark-fast twitch
– Light- slow twitch
• Acid pH (4.3)
– Dark-slow twitch
– Light-fast twitch
• Succinate dehydrogenase
– Krebs cycle enzyme
» Darkest type I
» Intermediate type IIa
» Lightest type IIb
© 2007 McGraw-Hill Higher Education. All rights reserved.
Muscle fiber typing
© 2007 McGraw-Hill Higher Education. All rights reserved.
Classification schemes
• How fast the respond
to a stimulus
– FT, ST
• How fast they fatigue
– Fatigue resistant,
fatiguable
• Oxidative capacity
• Color
• Function
• ATPase activity
© 2007 McGraw-Hill Higher Education. All rights reserved.
Size principle
• Recruitment of motor
units is based upon
– The size of the motor
unit
• Smaller motor units
more easily
recruited
– Thus, they are
recruited first
• Larger motor units
are recruited when
work needs are
(and thus neural
output) higher
© 2007 McGraw-Hill Higher Education. All rights reserved.