Download Sherwood 8

Chapter 8
Muscle Physiology
Outline
•
•
•
•
•
Structure
Contractile mechanisms
Mechanics
Control
Other muscle types
– Smooth, cardiac
Outline
• Structure
– Muscle fiber (from myoblasts)
– Myofibrils
– Thick and thin filaments (actin and myosin)
– A,H,M,I,Z
– Sarcomere
– Titin –elasticity
– Cross bridges
– Myosin, Actin, tropomyosin, troponin
Muscle
• Comprises largest group of tissues in body
• Three types of muscle
– Skeletal muscle
• Make up muscular system
– Cardiac muscle
• Found only in the heart
– Smooth muscle
• Appears throughout the body systems as components
of hollow organs and tubes
• Classified in two different ways
– Striated or unstriated
– Voluntary or involuntary
Unstriated
muscle
Striated
muscle
Skeletal muscle
Voluntary
muscle
Cardiac muscle
Smooth muscle
Involuntary
muscle
Fig. 8-1, p. 259
Muscle
• Controlled muscle contraction allows
– Purposeful movement of the whole body or parts
of the body
– Manipulation of external objects
– Propulsion of contents through various hollow
internal organs
– Emptying of contents of certain organs to external
environment
Structure of Skeletal Muscle
• Muscle consists a number of muscle fibers lying
parallel to one another and held together by
connective tissue
• Single skeletal muscle cell is known as a muscle
fiber
– Multinucleated
– Large, elongated, and cylindrically shaped
– Fibers usually extend entire length of muscle
Muscle
Tendon
Muscle fiber
(a single
muscle cell)
Connective
tissue
(a) Relationship of a whole muscle and a muscle fiber
Fig. 8-2a, p. 260
Structure of Skeletal Muscle
• Myofibrils
– Contractile elements of muscle fiber
– Regular arrangement of thick and thin filaments
• Thick filaments – myosin (protein)
• Thin filaments – actin (protein)
– Viewed microscopically myofibril displays
alternating dark (the A bands) and light bands
(the I bands) giving appearance of striations
Muscle
fiber
Dark A band
Light I band
Myofibril
(b) Relationship of
a muscle fiber and
a myofibril
Fig. 8-2b, p. 260
Structure of Skeletal Muscle
• Sarcomere
– Functional unit of skeletal muscle
– Found between two Z lines (connects thin filaments of two
adjoining sarcomeres)
– Regions of sarcomere
• A band
– Made up of thick filaments along with portions of thin filaments
that overlap on both ends of thick filaments
• H zone
– Lighter area within middle of A band where thin filaments do not
reach
• M line
– Extends vertically down middle of A band within center of H
zone
• I band
– Consists of remaining portion of thin filaments that do not
project into A band
Cross Thin
Thick
bridge filament filament
M line
Z line
A band
I band
Portion of
myofibril
H zone
Thick
filament
(c) Cytoskeletal
components of
a myofibril
Thin
filament
Sarcomere
M line
A band
Cross bridges H zone
I band
Z line
Fig. 8-2c, p. 260
Structure of Skeletal Muscle
• Titin
– Giant, highly elastic protein
– Largest protein in body
– Extends in both directions from M line along
length of thick filament to Z lines at opposite ends
of sarcomere
– Two important roles:
• Along with M-line proteins helps stabilize position of
thick filaments in relation to thin filaments
• Greatly augments muscle’s elasticity by acting like a
spring
Myosin
• Component of thick filament
• Protein molecule consisting of two identical subunits
shaped somewhat like a golf club
– Tail ends are intertwined around each other
– Globular heads project out at one end
• Tails oriented toward center of filament and globular
heads protrude outward at regular intervals
– Heads form cross bridges between thick and thin
filaments
• Cross bridge has two important sites critical to
contractile process
– An actin-binding site
– A myosin ATPase (ATP-splitting) site
Structure and Arrangement of Myosin
Molecules Within Thick Filament
Actin
• Primary structural component of thin filaments
• Spherical in shape
• Thin filament also has two other proteins
– Tropomyosin and troponin
• Each actin molecule has special binding site for
attachment with myosin cross bridge
– Binding results in contraction of muscle fiber
Actin molecules
Binding site for
attachment with myosin
cross bridge
Actin helix
Tropomyosin
Thin filament
Troponin
Fig. 8-5, p. 263
Actin and myosin are often called contractile
proteins. Neither actually contracts.
Actin and myosin are not unique to muscle cells,
but are more abundant and more highly
organized in muscle cells.
Tropomyosin and Troponin
• Often called regulatory proteins
• Tropomyosin
– Thread-like molecules that lie end to end
alongside groove of actin spiral
– In this position, covers actin sites blocking
interaction that leads to muscle contraction
• Troponin
– Made of three polypeptide units
• One binds to tropomyosin
• One binds to actin
• One can bind with Ca2+
Tropomyosin and Troponin
• Troponin
– When not bound to Ca2+, troponin stabilizes
tropomyosin in blocking position over actin’s
cross-bridge binding sites
– When Ca2+ binds to troponin, tropomyosin moves
away from blocking position
– With tropomyosin out of way, actin and myosin
bind, interact at cross-bridges
– Muscle contraction results
Tropomyosin
Myosin cross-bridge
binding sites
(a) Relaxed
(b)
Excited
Troponin
Actin
Actin-binding site
Myosin cross bridge
Cross-bridge interaction between actin and
myosin brings about muscle contraction by
means of the sliding filament mechanism.
Outline
Contractile mechanisms
• Sliding filament mechanism (Theory)
– Ca dependence
– Power stroke
– T tubules
– Ca release
• Lateral sacs, foot proteins, ryanodine receptors,
dihydropyradine receptors
– Cross bridge cycling
• Rigor mortis, relaxation, latent period
Sliding Filament Mechanism
• 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
Basic 4 steps
Fig. 8-8, p. 265
Transverse Tubules
• T tubules
• Run perpendicularly from surface of muscle cell
membrane into central portions of the muscle fiber
• Since membrane is continuous with surface
membrane – action potential on surface membrane
also spreads down into T-tubule
• Spread of action potential down a T tubule triggers
release of Ca2+ from sarcoplasmic reticulum into
cytosol
Surface membrane of muscle fiber
Myofibrils
Segments of
sarcoplasmic
reticulum
Lateral
sacs
Transverse (T)
tubule
I band
A band
I band
Fig. 8-9, p. 266
Sarcoplasmic Reticulum
• Modified endoplasmic reticulum
• Consists of fine network of interconnected
compartments that surround each myofibril
• Not continuous but encircles myofibril throughout its
length
• Segments are wrapped around each A band and
each I band
– Ends of segments expand to form saclike regions
– lateral sacs (terminal cisternae)
1
Acetylcholine
Terminal
button
Acetylcholine-gated
receptor-channel
for cations
2
Plasma membrane
of muscle cell
Neuromuscular
junction
Motor end
plate
Lateral sac of
sarcoplasmic
reticulum
T tubule
Ca2+
pump
Ca2+-release
channel
8
Troponin
Tropomyosin
Thin filament
Myosin
cross bridge
Actin molecule
Thick filament
3
Myosin crossbridge binding
Actin-binding
site
Cycle
repeats
4
7
6
5
Fig. 8-11, p. 268
1
Energized
...or... No Ca2+
2b
Resting
present (excitation)
4a
Detachment
Crossbridge
cycle
2a
Binding
Fresh ATP available
...or...
3
Bending
No ATP (after death)
4b
Rigor complex
Fig. 8-12, p. 269
Power Stroke
• Activated cross bridge bends toward center of thick
filament, “rowing” in thin filament to which it is
attached
• Sarcoplasmic reticulum releases Ca2+ into
sarcoplasm
• Myosin heads bind to actin
• Myosin heads swivel toward center of sarcomere
(power stroke)
• ATP binds to myosin head and detaches it from
actin
Power Stroke
• Hydrolysis of ATP transfers energy to myosin head
and reorients it
• Contraction continues if ATP is available and Ca2+
level in sarcoplasm is high
Sliding Filament Mechanism
• All sarcomeres throughout muscle fiber’s length
shorten simultaneously
• Contraction is accomplished by thin filaments from
opposite sides of each sarcomere sliding closer
together between thick filaments
Relaxation
• Depends on reuptake of Ca2+ into sarcoplasmic
reticulum (SR)
• Acetylcholinesterase breaks down ACh at
neuromuscular junction
• Muscle fiber action potential stops
• When local action potential is no longer present,
Ca2+ moves back into sarcoplasmic reticulum
Outline
• Mechanics
– Tendons
– Twitch
– Motor unit
– Motor unit recruitment
– Fatigue
– Asynchronous recruitment
– Twitch, tetanus, summation
– Muscle length, isometric, isotonic
• Tension, origin, insertion
Skeletal Muscle Mechanics
• Muscle consists of groups of muscle fibers bundled
together and attached to bones
• Connective tissue covering muscle divides muscle
internally into bundles
• Connective tissue extends beyond ends of muscle
to form tendons
– Tendons attach muscle to bone
Muscle Contractions
• Contractions of whole muscle can be of varying
strength
• Twitch
– Brief, weak contraction
– Produced from single action potential
– Too short and too weak to be useful
– Normally does not take place in body
• Two primary factors which can be adjusted to
accomplish gradation of whole-muscle tension
– Number of muscle fibers contracting within a
muscle
– Tension developed by each contracting fiber
Motor Unit Recruitment
• Motor unit
– One motor neuron and the muscle fibers it
innervates
• Number of muscle fibers varies among different
motor units
• Number of muscle fibers per motor unit and number
of motor units per muscle vary widely
– Muscles that produce precise, delicate
movements contain fewer fibers per motor unit
– Muscles performing powerful, coarsely controlled
movement have larger number of fibers per motor
unit
Motor Unit Recruitment
• Asynchronous recruitment of motor units helps delay
or prevent fatigue
• Factors influencing extent to which tension can be
developed
– Frequency of stimulation
– Length of fiber at onset of contraction
– Extent of fatigue
– Thickness of fiber
Motor neuron
Muscle fiber
Spinal cord
KEY
= Motor unit 1
= Motor unit 2
= Motor unit 3
Fig. 8-18, p. 274
Twitch Summation and Tetanus
• Twitch summation
– Results from sustained elevation of cytosolic
calcium
• Tetanus
– Occurs if muscle fiber is stimulated so rapidly that
it does not have a chance to relax between
stimuli
– Contraction is usually three to four times stronger
than a single twitch
Tetanus
Membrane
potential (mV)
Contractile
activity
Relative tension
3
Action
potentials
2
Single
twitch
Stimulation
ceases or
fatigue
begins
Twitch
summation
1
0
+30
0
–90
If a muscle fiber is
restimulated after it has
completely relaxed, the
second twitch has the
same magnitude as the
first twitch.
If a muscle fiber is
If a muscle fiber is stimulated
restimulated before it so rapidly that it does not have
has completely relaxed, an opportunity to relax at all
the second twitch is
between stimuli, a maximal
added on to the first
sustained contraction known as
twitch, resulting in
tetanus occurs.
summation.
Time
(a) No summation
(b) Twitch summation
(c) Tetanus
Fig. 8-20, p. 276
Muscle Tension
• Tension is produced internally within sarcomeres
• Tension must be transmitted to bone by means of
connective tissue and tendons before bone can be
moved (series-elastic component)
• Muscle typically attached to at least two different
bones across a joint
– Origin
• End of muscle attached to more stationary part of
skeleton
– Insertion
• End of muscle attached to skeletal part that moves
Percent maximal (tetanic) tension
Range of length
changes that can
occur in the body
A
100%
D
B
C
50%
I0
(resting muscle length)
70%
100%
Shortened
muscle
130%
Stretched
muscle
170%
Muscle fiber length compared with resting length
Fig. 8-21, p. 277
Types of Contraction
• Two primary types
– Isotonic
• Muscle tension remains constant as muscle changes
length
– Isometric
• Muscle is prevented from shortening
• Tension develops at constant muscle length
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
Energy Sources for Contraction
• Transfer of high-energy phosphate from creatine
phosphate to ADP
– First energy storehouse tapped at onset of
contractile activity
• Oxidative phosphorylation (citric acid cycle and
electron transport system
– Takes place within muscle mitochondria if
sufficient O2 is present
• Glycolysis
– Supports anaerobic or high-intensity exercise
Muscle Fatigue
• Occurs when exercising muscle can no longer
respond to stimulation with same degree of
contractile activity
• Defense mechanism that protects muscle from
reaching point at which it can no longer produce
ATP
• Underlying causes of muscle fatigue are unclear
Central Fatigue
• Occurs when CNS no longer adequately activates
motor neurons supplying working muscles
• Often psychologically based
• Mechanisms involved in central fatigue are poorly
understood
Outline
• Other types
– Fibers
•
•
•
•
Fast
slow
Oxidative
glycolytic
– Smooth, cardiac
– Creatine phosphate
– Oxidative phosphorulation
• Aerobic, myoglobin
– Glycolysis
• Anaerobic, lactic acid
Major Types of Muscle Fibers
• Classified based on differences in ATP hydrolysis
and synthesis
• Three major types
– Slow-oxidative (type I) fibers
– Fast-oxidative (type IIa) fibers
– Fast-glycolytic (type IIx) fibers
Characteristics of Skeletal
Muscle Fibers
Control of Motor Movement
• Three levels of input control motor-neuron output
– Input from afferent neurons
– Input from primary motor cortex
– Input from brain stem
Table 8-1 p282
Table 8-2 p285
Control of Motor Movement
• Control of motor movement depends on activity in
three types of inputs:
– input of afferent neurons associated with spinal
reflexes
– input from the primary motor cortex, concerned
with complex, controlled movements
– input from the brain stem (multineuronal motor
system) involved in posture
Premotor
cortex
Premotor and
supplementary motor areas
Primary Somatosensory
motor cortex
cortex
Cortical
level
Sensory areas
of cortex
Subcortical
level
Basal nuclei
Basal
nuclei
Primary motor cortex
Thalamus
Brain stem
level
Cerebellum
Brain stem nuclei
(including reticular formation
and vestibular nuclei)
Thalamus
Brain stem
Cerebellum
Spinal cord
2c
2a
Spinal cord
level
Afferent neuron
terminals
2b
Motor neurons
1
2
Peripheral
receptors
Muscle fibers
Periphery
Movement
Other peripheral events,
such as visual input
Sensory consequences
of movement
Fig. 8-24, p. 288
Muscle Receptors
• Two types of muscle receptors.
• Both are activated by muscle stretch, but monitor
different types of information.
• Muscle spindles monitors muscle length.
• Golgi tendon organs detect changes in tension.
Muscle Spindle
• Spindles consist of collections of specialized muscle
fibers known as intrafusal fibers.
• Lie within spindle-shaped connective tissue
capsules parallel to extrafusal fibers.
• Each spindle has its own private efferent and
afferent nerve supply
• Contain both afferent and efferent nerve fibers.
• Plays key role in stretch reflex.
Capsule
Alpha motor
neuron axon
Intrafusal (spindle)
muscle fibers
Gamma motor
neuron axon
Afferent neuron
axons
Primary
(annulospiral)endings of
afferent fibers
Contractile end
portions of intrafusal
fiber
Noncontractile
central portion
of intrafusal
fiber
Secondary (flower-spray)
endings of afferent fibers
Extrafusal (“ordinary”)
muscle fibers
Fig. 8-25a, p. 289
Skeletal muscle
Afferent fiber
Golgi tendon organ
Collagen
Tendon
Bone
(b) Golgi tendon organ
Fig. 8-25b, p. 289
Stretch Reflex
• Primary purpose is to resist tendency for passive
stretch of extensor muscles by gravitational forces
when person is standing upright
• Classic example is patellar tendon, or knee-jerk
reflex
Outline
• Other muscle types
– Smooth muscle
– Cardiac muscle
Smooth Muscle
• Found in walls of hollow organs and tubes.
• Contains actin and myosin but not troponin, and
tropomyosin.
• Does not form myofibrils and not arranged into
sarcomeres.
• Cells usually arranged in sheets.
Smooth Muscle
• Cell has three types of filaments
– Thick myosin filaments
• Longer than those in skeletal muscle
– Thin actin filaments
• Contain tropomyosin but lack troponin
– Filaments of intermediate size
• Do not directly participate in contraction
• Form part of cytoskeletal framework that supports cell
shape
Dense
body Bundle of thick
and thin filaments
Plasma
membrane Thin
filament
One relaxed contractile unit
extending from side to side
One contracted
contractile unit
Thick
filament
Thin
filament
Thick
filament
(a) Relaxed smooth muscle cell
(b) Contracted smooth muscle cell
Fig. 8-29, p. 295
Calcium Activation of Myosin Cross Bridge in Smooth Muscle
Calmodulin
Inactive myosin
light chain kinase
Ca2+–calmodulin
Active myosin
light chain kinase
Inactive myosin
cross bridge
Phosphorylated
myosin cross bridge
(can bind with actin)
Permits binding
with actin
Part of
crossbridge
energy
cycle
Myosin light chain
Fig. 8-30, p. 296
Types of Smooth Muscle
Single-unit Smooth Muscle
•
•
•
•
•
•
Self-excitable (does not require
nervous stimulation for
contraction)
Also called visceral smooth
muscle
Fibers become excited and
contract as single unit
Cells electrically linked by gap
junctions
Can also be described as a
functional syncytium
Contraction is slow and energyefficient
– Well suited for forming walls of
distensible, hollow organs
Multiunit Smooth Muscle
• Neurogenic
• Consists of discrete units that
function independently of one
another
• Units must be separately
stimulated by nerves to
contract
• Found
– In walls of large blood vessels
– In large airways to lungs
– In muscle of eye that adjusts
lens for near or far vision
– In iris of eye
– At base of hair follicles
Cardiac muscle
Smooth muscle
Skeletal muscle
Muscle excitation
Muscle excitation
Rise in cytosolic Ca2+
(mostly from
extracellular fluid)
Series of
biochemical events
Phosphorylation of
myosin cross bridges
in thick filament
Binding of actin and
myosin at cross
bridges
Rise in cytosolic Ca2+
(entirely from intracellular
sarcoplasmic reticulum)
Comparison of the
Role of Calcium In
Bringing About
Contraction in
Smooth, Skeletal,
and Cardiac
Muscle
Physical repositioning
of troponin and
tropomyosin
Uncovering of crossbridge binding sites on
actin in thin filament
Binding of actin and
myosin at cross
bridges
Pi
Fig. 8-31, p. 296
Contraction
Contraction
Cardiac Muscle
•
•
•
•
•
Found only in walls of heart
Striated
Cells are interconnected by gap junctions
Fibers are joined in branching network
Innervated by autonomic nervous system
Cardiac Muscle Fibers
• Interconnected by intercalated discs and form
functional syncytia
• Within intercalated discs – two kinds of membrane
junctions
– Desmosomes
– Gap junctions
• Ap’s
Ionic mechanisms of cardiac AP
• Rp is -85 to -95 MV in atrial fibers; -90-100 mv in
purkinje fibers
• Ap controlled by
– Fast Na /Slow Ca channels
– Channels stay open longer - creates plateau
– Prolonged depolarizarion
– Refractory period
Excitation contraction coupling
• Ca sources:
– T tubules connected to Sarcoplasmic membrane
– ECF Ca influences contraction
– Larger T tubules hold more Ca
• Neg. charged molecules sequester Ca
Cell types coordinate function
• Fast response
cells
• Slow response
cells
• Atria and ventricles
• Rp -80 to -90mv
• Do not spontaneously
depolarize
• Short refractory
period
• Fast conduction
velocity
• Conductive system
• Rp -55 to -60 mV
• spontaneously
depolarize
• Long refractory period
• Slow conduction
velocity
Banding
Calcium Release 1
Calcium Release 2
Crossbridge Interaction
Capsule
Alpha motor
neuron axon
Gamma motor
neuron axon
Secondary (flower-spray)
endings of afferent
fibers
Extrafusal (“ordinary”)
muscle fibers
Intrafusal (spindle)
muscle fibers
Contractile end portions
of intrafusal fiber
Noncontractile
central portion
of intrafusal
fiber
Primary (annulospiral)
endings of afferent fibers
Fig. 8-24, p. 283
Smooth Muscle
• Two major types
– Multiunit smooth muscle
– Single-unit smooth muscle
Multiunit Smooth Muscle
• Neurogenic
• Consists of discrete units that function
independently of one another
• Units must be separately stimulated by nerves to
contract
• Found
– In walls of large blood vessels
– In large airways to lungs
– In muscle of eye that adjusts lens for near or far
vision
– In iris of eye
– At base of hair follicles
Single-unit Smooth Muscle
• Self-excitable (does not require nervous stimulation
for contraction)
• Also called visceral smooth muscle
• Fibers become excited and contract as single unit
• Cells electrically linked by gap junctions
• Can also be described as a functional syncytium
• Contraction is slow and energy-efficient
– Well suited for forming walls of distensible, hollow
organs