Download Chapter 8 - Muscle Physiology

BIO2305
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Muscle Physiology
Muscle accounts for nearly half of the body’s mass - Muscles have the ability to change
chemical energy (ATP) into mechanical energy
Three types of Muscle Tissue – differ in structure, location, function, and means of activation
1. Skeletal Muscle
2. Cardiac Muscle- forms most of the heart, it is striated, involuntary, autorhythmic
3. Smooth Muscle- located in the walls of hollow internal structures, nonstriated,
involuntary
Skeletal Muscle
• Skeletal muscles attach to and cover the bony skeleton
• Is controlled voluntarily (i.e., by conscious control)
• Contracts rapidly but tires easily
• Is responsible for overall body motility
• Is extremely adaptable and can exert forces ranging from a fraction of an ounce to over 70
pounds
• Has obvious stripes called striations
• Each muscle cell is multinucleated
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Sarcolemma
 A muscle fiber plasma (cell) membrane
Sarcoplasm
 Muscle fiber cytoplasm, almost completely filled with contractile filaments called
myofilaments (thick, thin & elastic)
 Sarcoplasm contains glycosomes (granules of glycogen) and the oxygen-binding protein called
myoglobin
 In addition to the typical organelles, fibers have
o Sarcoplasmic reticulum
o T tubules - modifications of the sarcolemma
o Myofibrils
 Each muscle fiber is made of many myofibrils, 80% of the muscle volume, that contain the
contractile elements of skeletal muscle cells
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Myofibrils – Striations
• Myofibrils are made up of 2 types of contractile proteins called myofilaments
• Thick (Myosin) filaments
• Thin (Actin) filaments
• The arrangement of myofibrils creates a series of repeating dark A (anisotropic) bands and
light I (isotropic) bands
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The A band has a light stripe in the center called the H (helle) zone
The H zone is bisected by a dark line, the M line
I band has a darker midline called the Z disc (or Z line)
Sarcomere
• Smallest contractile unit of a muscle
• Myofibril region between two successive Z discs, has a central A band and partial (half) I bands
at each end
• Characterized by alternating light and dark bands or zones produced by the myofilaments
• Z disc - a line that separates one sarcomere from another
• M line - central line of the sarcomere where myosin filaments are anchored
• H zone - the area where only myosin filaments are present
• I band - the area where only actin filaments are present
• A band - includes overlapping myosin and actin filaments
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Thick Filaments (16 nm diam) Myosin
• Each myosin molecule (two interwoven polypeptide chains) has a rod-like tail and two globular
heads
• During muscle contraction, the heads link the thick and thin filaments together, forming cross
bridges
Thin Filaments - Actin
• Thin filaments are mostly composed of the protein actin.
• Provides active sites where myosin heads attach during contraction. Tropomyosin and
Troponin are regulatory subunits bound to actin.
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A band
(c)
Ultrastructure of Muscle
Sarcomere
Z disk
Z disk
Myofibril
M line
I band
H zone
(d)
Titin
Z disk
M line
Z disk
M line
Thin filaments
Thick filaments
(f)
(e)
Myosin
heads
Hinge
Myosin tail region
Titin
Tropomyosin
Troponin Nebulin
G-actin molecule
Actin chain
Myosin molecule
Arrangement of Filaments in a Sarcomere
Sarcoplasmic reticulum (endoplasmic reticulum)
 A network of tubes surrounding myofibrils, functions to reabsorb calcium ion during
relaxation, release them to cause contraction.
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
SR - an elaborate, smooth ER that surrounds each myofibril. Perpendicular (transverse)
channels at the A band - I band junction are the Terminal Cisternae (Lateral Sacs) SR regulates
intracellular Ca2+
T tubules at each A band/I band junction - continuous with the sarcolemma. Conduct electrical
impulses to the throughout cell (every sarcomere) - signals for the release of Ca2+ from
adjacent terminal cisternae
Transverse tubules
 Tubules formed by invaginations of the sarcolemma and flanked by the sarcoplasmic reticulum
 They carry action potentials deep into the muscle fiber.
 T tubules and SR provide tightly linked signals for muscle contraction.
Triad – 2 terminal cisternae and 1 T tubule
• T tubules and SR provide tightly linked signals for muscle contraction
• Interaction of integral membrane proteins (IMPs) from T tubules and SR
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Interaction of T-Tubule Proteins and SR Foot Proteins
• T tubule proteins (Dihydropyridine) act as voltage sensors
• SR foot proteins are (ryanodine) receptors that regulate Ca2+ release from the SR cisternae
• Action potential in t-tubule alters conformation of DHP receptor
• DHP receptor opens Ca2+ release channels in sarcoplasmic reticulum and Ca2+ enters
cytoplasm
(b)
DHP receptor
SR Foot Protein (Ca++ release channel)
Ca2+
Ca2+
released
Sliding Filament Model of Contraction
• Contraction refers to the activation of myosin’s cross bridges – the sites that generate the force
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In the relaxed state, actin and myosin filaments do not fully overlap
With stimulation by the nervous system, myosin heads bind to actin and pull the thin filaments
Actin filaments slide past the myosin filaments so that the actin and myosin filaments overlap
to a greater degree (the actin filaments are moved toward the center of the sarcomere, Z lines
become closer)
Skeletal Muscle Contraction
• For contraction to occur, a skeletal muscle must:
• Be stimulated by a nerve ending
• Propagate an electrical current, or action potential, along its sarcolemma
• Have a rise in intracellular Ca2+ levels, the final stimulus for contraction
• The series of events linking the action potential to contraction is called excitation-contraction
coupling
• Individual muscle fibers contract to their fullest extent; they do not partially contract, this
follows the all or none principle.
Depolarization and Generation of an AP
• The sarcolemma, like other plasma membranes is polarized. There is a potential difference
(voltage) across the membrane
• When Ach binds to its receptors on the motor end plate, chemically (ligand) gated ion channels
in the receptors open and allow Na+ and K+ to move across the membrane, resulting in a
transient change in membrane potential - Depolarization
• End plate potential - a local depolarization that creates and spreads an action potential across
the sarcolemma
Excitation-Contraction Coupling
• E-C Coupling is the sequence of events linking the transmission of an action potential along the
sarcolemma to muscle contraction (the sliding of myofilaments)
• The action potential lasts only 1-2 ms and ends before contraction occurs.
• The period between action potential initiation and the beginning of contraction is called the
latent period.
• E-C coupling occurs within the latent period.
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Regulatory Role of Tropomyosin and Troponin
(b) Initiation of contraction
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Ca2+ levels increase
in cytosol.
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Ca2+ binds to
troponin.
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4 Power stroke
3
Tropomyosin shifts,
exposing binding
site on G-actin
Troponin-Ca2+
complex pulls
tropomyosin
away from G-actin
binding site.
Pi
ADP
TN
4
Myosin binds
to actin and
completes power
stroke.
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2
5
G-actin moves
Actin filament
moves.
Cytosolic Ca2+
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Excitation-Contraction Coupling
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Somatic motor neuron
releases ACh at neuromuscular junction.
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(a)
Net entry of Na+ through ACh
receptor-channel initiates
a muscle action potential.
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Axon terminal of
somatic motor neuron
ACh
Muscle fiber
n
2
potential
tio
Ac
K+
Action potential
Na+
Motor end plate
Sarcoplasmic reticulum
T-tubule
Ca2+
DHP
receptor
Tropomyosin
Z disk
Troponin
Actin
M line
Myosin
head
Myosin thick filament
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Excitation-Contraction Coupling
 The AP lasts only 1-2 ms and ends before contraction occurs. The period between action
potential initiation and the beginning of contraction is called the latent period. E-C coupling
occurs within the latent period.
 The action potential is propagated along (across) the sarcolemma and travels through the T
tubules
 At the triads, the action potential causes voltage sensitive T tubule proteins to change shape.
This change, in turn, causes the SR foot proteins of the terminal cisternae to change shape,
Ca2+ channels are opened and Ca2+ is released into the sarcoplasm (where the myofilaments
are)
T tubule
Terminal button
Surface membrane of muscle cell
Acetylcholine
Acetylcholinegated cation
channel
Tropomyosin
Actin
Troponin
Cross-bridge binding
Myosin cross bridge
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Some of the Ca2+ binds to troponin, troponin changes shape and causes tropomysin to move
which exposes the active binding sites on actin
Myosin heads can now alternately attach and detach, pulling the actin filaments toward the
center of the sarcomere (ATP hydrolysis is necessary)
• The ATP attached to the myosin head is split by ATPase causing the myosin heads to be
activated.
• The activated myosin head attaches to the actin binding site, then swivels, producing a
power stroke which results in the sliding of the filaments. The ADP and P are released.
Contraction refers to the activation of myosin’s cross bridges – the sites that generate
the force
• Once the power stroke is complete, ATP again attaches to the myosin head causing the
head to detach from the actin site and return to its original position.
• Cycle can then be repeated over and over again as long as calcium and ATP are present.
Relaxation is caused by the breaking down of ACh by the enzyme acetylcholinesterase and the
reabsorption of calcium back into the SR
• The short calcium influx ends (30 ms after the action potential ends) and Ca2+ levels
fall. An ATP-dependent Ca2+ pump is continually moving Ca2+ back into the SR.
• Tropomyosin blockage of the actin binding sites is reestablished as Ca2+ levels drop.
Cross bridge activity ends and relaxation occurs
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The Molecular Basis of Contraction
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Myosin filament
1
Tight binding in the rigor
state. The crossbridge is
at a 45° angle relative to
the filaments.
Myosin
binding
sites
1
45°
ATP
binding
site
3
2
4
2
ATP binds to its binding site
on the myosin. Myosin then
dissociates from actin.
G-actin molecule
ADP
1
2
3
4
ATP
1
5
6 At the end of the power stroke,
the myosin head releases ADP
and resumes the tightly bound
rigor state.
3
2
3
4
Actin filament
moves toward M line.
90°
5 Release of Pi initiates the power
stroke. The myosin head rotates
on its hinge, pushing the actin
filament past it.
1
4
ADP
Pi
Sliding
filament
5
3
The ATPase activity of myosin
hydrolyzes the ATP. ADP and
Pi remain bound to myosin.
Contractionrelaxation
Pi
1
2
1
2
3
4
Pi
2
3
4
4
The myosin head swings over and
binds weakly to a new actin molecule.
The crossbridge is now at 90º relative
to the filaments.
Sequential Events of Contraction
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Motor Unit
• 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
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Electrical and Mechanical Events in Muscle Contraction
A twitch is a single contraction-relaxation cycle
Muscle Twitch
• A muscle twitch is the response of the muscle fibers of a motor unit to a single action potential
of its motor neuron. The fibers contract quickly and then relax. Three Phases:
• Latent Period – time elapsed from the application of a stimulus to the beginning of the
contraction (when Ca is being released); it’s the first few ms after stimulation when excitationcontraction is occurring
• Period of Contraction – cross bridges are active and the muscle shortens if the tension is great
enough to overcome the load
• Period of Relaxation – Ca2+ is pumped back into SR, degradation of ACh and muscle tension
decreases to baseline level
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Graded muscle responses
• Graded muscle responses are:
• Variations in the degree or strength of muscle contraction in response to demand
• Required for proper control of skeletal movement
• Muscle contraction can be graded (varied) in two ways:
• Changing the frequency of the stimulus
• Changing the strength of the stimulus
Motor unit recruitment - The process of increasing the number of active motor units in a muscle
for stronger contractions
Muscle Response to Stimulation Frequency
• A single stimulus results in a single contractile response – a muscle twitch (contracts and
relaxes)
• More frequent stimuli increases contractile force – wave summation - muscle is already
partially contracted when next stimulus arrives and contractions are summed
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More rapidly delivered stimuli result in incomplete tetanus – sustained but quivering
contraction
If stimuli are given quickly enough, complete tetanus results – smooth, sustained contraction
with no relaxation period
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Summation & Tetanus
• A sustained contraction that lacks even partial relaxation is known as tetanus
Factors Affecting Force of Muscle Contraction
• Number of motor units recruited, recruitment also helps provide smooth muscle action rather
than jerky movements
• The relative size of the muscle fibers – the bulkier the muscle fiber (greater cross-sectional
area), the greater its strength
• Asynchronous recruitment of motor units –Used to prevent fatigue; while some motor units
are active others are inactive- this pattern of firing provides a brief rest for the inactive units
preventing fatigue while maintaining contraction by allowing a brief rest for the inactive units.
• Degree of muscle stretch
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Length-Tension Relationship
Muscle tone
• The constant, slightly contracted state of all muscles
• Does not produce active movements
• Keeps the muscles firm and ready to respond to stimulus
• Helps stabilize joints and maintain posture
• Due to spinal reflex activation of motor units in response to stretch receptors in muscles and
tendons
Contraction of Skeletal Muscle Fibers
• The force exerted on an object by a contracting muscle is called muscle tension, the opposing
force or weight of the object to be moved is called the load.
• Two types of Muscle Contraction:
1. When muscle tension develops, but the load is not moved (muscle does not shorten) the
contraction is called Isometric
2. If muscle tension overcomes (moves) the load and the muscle shortens, the contraction
is called Isotonic
Isometric Contractions
• The muscle does not or cannot shorten, but the tension on the muscle increases, no change in
length
• In isometric contractions, increasing muscle tension (force) is measured
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Isotonic Contractions
• In isotonic contractions, the muscle changes length and moves the load. Once sufficient
tension has developed to move the load, the tension remains relatively constant through the
rest of the contractile period. In isotonic contractions, the amount of shortening (distance in
mm) is measured.
• Two types of isotonic contractions:
• Concentric contractions – the muscle shortens and does work
• Eccentric contractions – the muscle contracts as it lengthens
Concentric Isotonic Contraction
Energy Sources for Contraction
• ATP is the only energy source that is used directly for contractile activity
• As soon as available ATP is hydrolyzed (4-6 seconds), it is regenerated by three pathways:
• 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
CP-ADP Reaction
• Transfer of energy as a phosphate group is moved from CP to ADP – the reaction is catalyzed
by the enzyme creatine kinase
• Creatine phosphate + ADP → creatine + ATP
• Stored ATP and CP provide energy for maximum muscle power for 10-15 seconds
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Anaerobic Glycolysis
• Glucose is broken down into pyruvic acide to yield 2 ATP
• When oxygen demand cannot be met, pyruvic acid is converted into lactic acid
• Lactic acid diffuses into the bloodstream – can be used as energy source by the liver, kidneys,
and heart
• Can be converted back into pyruvic acid, glucose, or glycogen by the liver
Glycolysis and Aerobic Respiration
• Aerobic respiration occurs in mitochondria - requires O2
• A series of reactions breaks down glucose for high yield of ATP
• Glucose + O2 → CO2 + H2O + ATP
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Muscle Fatigue
• Muscle fatigue – the muscle is physiologically not able to contract
• Occurs when oxygen is limited and ATP production fails to keep pace with ATP use
• Lactic acid accumulation and ionic imbalances may also contribute to muscle fatigue
• Depletion of energy stores – glycogen
• When no ATP is available, contractures (continuous contraction) may result because cross
bridges are unable to detach
• Ionic imbalance, neural fatigue
• Central Fatigue – psychological, it hurts
For a muscle to return to its pre-exercise state:
- Oxygen reserves must be replenished
- (Lactic acid must be converted to pyruvic acid?)
- Glycogen stores must be replaced
- ATP and CP reserves must be resynthesized
Oxygen debt – the extra amount of O2 needed for the above restorative processes
Muscle Fiber Types: Speed of Contraction
• Speed of contraction – determined by how fast their myosin ATPases split ATP
• Oxidative fibers – use aerobic pathways
• Glycolytic fibers – use anaerobic glycolysis
• Based on these two criteria skeletal muscles may be classified as:
• Slow oxidative fibers (Type I) - contract slowly, have slow acting myosin ATPases, and
are fatigue resistant; postural muscle groups
• Fast oxidative fibers (Type IIA)- contract quickly, have fast myosin ATPases, and have
moderate resistance to fatigue; Abundant is muscle groups requiring speed (sprinter)
• Fast glycolytic fibers (Type IIB)- contract quickly, have fast myosin ATPases, and are
easily fatigued; large diameter fibers used in muscles requiring strong and rapid, but
brief contractions (arms)
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Smooth Muscle
• Occurs within most organs
• Walls of hollow visceral organs, such as the stomach
• Urinary bladder
• Respiratory passages
• Arteries and veins
• Helps substances move through internal body channels via peristalsis
• No striations
• Filaments do not form myofibrils
• Not arranged in sarcomere pattern found in skeletal muscle
• Is Involuntary
• Single Nucleus
Smooth Muscle contraction
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Composed of spindle-shaped fibers with a diameter of 2-10 m and lengths of several hundred
m
Cells usually arranged in sheets within muscle
Organized into two layers (longitudinal and circular) of closely apposed fibers
Have essentially the same contractile mechanisms as skeletal muscle
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
• Have dense bodies containing same protein found in Z lines
Contraction of Smooth Muscle
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Whole sheets of smooth muscle exhibit slow, synchronized contraction
Smooth muscle lacks neuromuscular junctions
Action potentials are transmitted from cell to cell
Some smooth muscle cells:
• Act as pacemakers and set the contractile pace for whole sheets of muscle
• Are self-excitatory and depolarize without external stimuli
Stimuli Influencing Smooth Muscle
Contractile Activity
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Muscle fiber stimulated
Ca2+ released into the cytoplasm from ECF
Ca2+ binds with calmodulin
Ca2+/Calmodulin activates mysoin kinase
Myosin kinase phosphorylates myosin
Myosin can now bind with actin
Smooth Muscle Contraction
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ECF
Ca2+
Sarcoplasmic
reticulum
1 Intracellular Ca2+
concentrations increase
when Ca2+ enters cell
and is released from
sarcoplasmic reticulum.
1
Ca2+
Ca2+
CaM
Pi
2
Pi
Ca2+
2 Ca2+ binds to
calmodulin (CaM).
CaM
Inactive
MLCK
3
3 Ca2+–calmodulin
activates myosin light
chain kinase (MLCK).
Active
MLCK
ATP
4
ADP +
P
Active myosin
ATPase
Inactive myosin
P
4 MLCK phosphorylates
light chains in myosin
heads and increases
myosin ATPase activity.
Actin
5
Increased
muscle
tension
5 Active myosin
crossbridges slide
along actin and create
muscle tension.
Comparison of Role of Calcium in Bringing About
Contraction in Smooth Muscle and Skeletal Muscle
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Cardiac Muscle Tissue
• Occurs only in the heart
• Is striated like skeletal muscle but has a branching pattern with intercalated Discs
• Usually one nucleus, but may have more
• Is not voluntary
• Contracts at a fairly steady rate set by the heart’s pacemaker
• Neural controls allow the heart to respond to changes in bodily needs
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