Muscle Physiology
Muscle Tissue
• 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
• Skeletal Muscle
• Cardiac Muscle
• Smooth Muscle
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
Microscopic Anatomy - Skeletal Muscle Fiber
•
•
Sarcoplasm contains glycosomes (granules of glycogen) and the oxygen-binding
protein called myoglobin
In addition to the typical organelles, fibers have
•
•
•
•
Sarcoplasmic reticulum
T tubules - modifications of the sarcolemma
Myofibrils
Each muscle fiber is made of many myofibrils, 80% of the muscle volume, that
contain the contractile elements of skeletal muscle cells
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
Myofibrils - Striations
• 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
Thick Filaments (16 nm diam) Myosin
• Each myosin molecule (two interwoven polypeptide chains)
has a rodlike 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.
Ultrastructure of Muscle
Sarcomere
A band
(c)
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
Myosin molecule
Titin
Tropomyosin
Troponin Nebulin
G-actin molecule
Actin chain
Figure 12-3c–f
Arrangement of Filaments in a Sarcomere
Sarcoplasmic Reticulum (SR)
•
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
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
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
• 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)
Sliding Filament Model of Contraction
Sliding Filament Model of Contraction
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
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.
Regulatory Role of Tropomyosin and Troponin
(b) Initiation of contraction
1
Ca2+ levels increase
in cytosol.
2
Ca2+ binds to
troponin.
3
Troponin-Ca2+
complex pulls
tropomyosin
away from G-actin
binding site.
4 Power stroke
3
Tropomyosin shifts,
exposing binding
site on G-actin
Pi
ADP
TN
4
Myosin binds
to actin and
completes power
stroke.
5
2
5
Actin filament
moves.
G-actin moves
1
Cytosolic Ca2+
Figure 12-10b, steps 1–5
Excitation-Contraction Coupling
1
Somatic motor neuron
releases ACh at neuromuscular junction.
2
(a)
Net entry of Na+ through ACh
receptor-channel initiates
a muscle action potential.
1
Axon terminal of
somatic motor neuron
ACh
Muscle fiber
potential
K+
2
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
Figure 12-11a, steps 1–2
Excitation-Contraction Coupling
•
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
Excitation-Contraction Coupling
•
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)
Excitation-Contraction Coupling
• 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
The Molecular Basis of Contraction
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
2 3 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.
1
2
3
4
3
Pi
Contractionrelaxation
5
Sliding
filament
Actin filament
moves toward M line.
Release of Pi initiates the power
5
stroke. The myosin head rotates
on its hinge, pushing the actin
filament past it.
90°
1
2
3
4
The ATPase activity of myosin
hydrolyzes the ATP. ADP and
Pi remain bound to myosin.
ADP
Pi
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.
Figure 12-9
Sequential Events
of Contraction
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
Electrical and Mechanical Events
in Muscle Contraction
A twitch is a single contraction-relaxation cycle
Figure 12-12
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 – the first few ms after
stimulation when excitation-contraction
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 and muscle tension
decreases to baseline level
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
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
Muscle Response to Stimulation Frequency
• 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
Summation and 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 -while some motor units are
active others are inactive - this pattern of firing provides a brief rest for
the inactive units preventing fatigue
• Degree of muscle stretch
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:
• When muscle tension develops, but the load is not moved (muscle
does not shorten) the contraction is called Isometric
• If muscle tension overcomes (moves) the load and the muscle
shortens, the contraction is called Isotonic
Isometric Contractions
No change in overall muscle length
In isometric contractions, increasing muscle tension
(force) is measured
Isotonic Contraction
• 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.
• Two types of isotonic contractions:
• Concentric contractions – the muscle shortens and
does work
• Eccentric contractions – the muscle contracts as it
lengthens
Isotonic Contraction
This illustrates a concentric isotonic contraction
In isotonic contractions, the amount of shortening
(distance in mm) is measured
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
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
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
Muscle Fiber Type: 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
• Fast oxidative fibers (Type IIA)contract quickly, have fast myosin
ATPases, and have moderate
resistance to fatigue
• Fast glycolytic fibers (Type IIB)contract quickly, have fast myosin
ATPases, and are easily fatigued
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
• 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
• 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
Smooth Muscle
• 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
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.
Figure 12-28, steps 1–5
Comparison of Role of
Calcium In Bringing About
Contraction in Smooth
Muscle and Skeletal Muscle
Cardiac Muscle Tissue
• Occurs only in the heart
• Is striated like skeletal muscle but
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