MUSCLE Chpt 11
Muscle cells are responsible for producing coordinated movements
Three basic types of muscles:
1) Skeletal muscle: attached to bone or connective tissue; voluntary -
gross body movement
2) Smooth muscle: contractile cells incorporated into organs like
digestive tract, urinary bladder, uterus, blood vessels, lungs
3) Cardiac muscle: Heart muscle.
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Skeletal muscle exhibits the basic muscle structure
1] Muscle fiber: single cell that usually (but not always) runs the
length of the muscle itself (i.e. tendon to tendon)
2] Each muscle fiber has many nuclei; this is because a muscle fiber is
formed by the fusion of many cells (called myoblasts) during embryonic
development.
3] Examination of a muscle fiber under a microscope reveals that the
fiber has a banded appearance (bands run perpendicular to the direction of
fiber length); gives muscle a striped appearance, thus these fibers are
referred to as striated muscle. (found in both skeletal and cardiac muscle)
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What gives these fibers their striated appearance? Figs 11-3 to 15
1] Within the cytoplasm of each fiber (cell), there are numerous
filaments organized into bundles that run the length of the muscle
Each of these bundles is known as a myofibril.
2] Myofibrils are cylindrical, striated contractile elements that fill
most of the cytoplasm (sarcoplasm) of the muscle fiber.
3] A single functional unit of striated muscle is called a sarcomere
(sarco = muscle, mere = small)
4] Sarcomeres are composed of repeating groups of fiberlike proteins.
Myosin: thick filaments
Actin: thin filaments (about 1/2 diameter of myosin)
Other proteins (titin, troponin, tropomyosin) play regulatory roles
Fig 5
5] Thick and thin filaments within a sarcomere are arranged in a
repeating pattern:
thick myosin filaments make a wide dark band in the center of the
sarcomere (the A band)
thin actin filaments make up a two lighter bands on each end of
the sarcomere (the I band).
6] Z line - a network of interconnected proteins where sarcomeres are
attached to one another
7] Close examination reveals that the myosin filaments have little
projections along their length.
These projections are known as cross-bridges and will be sites of
interaction between myosin and actin fibers.
The binding of these cross-bridges to actin and their movement,
fueled by ATP, is the direct cause of muscle contraction.
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What is the molecular mechanisms of contraction?
Contraction: the turning on of force generating sites (cross-bridges)...
not necessarily "shortening"
Relaxation: turning off of force generating sites.
1] The sliding filament mechanism F 11-12 modified
a] When these cross-bridges are activated they move, the net result
is that overlapping filaments of actin and myosin slide past one another
The filaments themselves do not change length, but rather move
past one another.
b] During muscle shortening, the cross-bridges from myosin bind to
actin and pull actin filaments toward the center of the sarcomere (toward
the M line)
c] To fully shorten a muscle, cross-bridges repeat the binding and
swiveling motion many times.
2] How does this happen? Cross-bridge cycle
a] The start of the cycle requires that ATP binds to the cross-bridge
head, which releases it from actin (cross-bridge attached to a thin filament
= default) (3)
b] Intrinsic myosin ATPase activity splits the ATP (4, 1)
The activated myosin still has ADP and Pi bound to it
The energized myosin head moves toward the z-line and binds
weakly to actin
c] Cross-bridge power stroke (2)
The binding of myosin to actin triggers the release of additional
energy stored in the myosin, and the Pi is released
The myosin head rotates on its hinge, pulling the actin filament
toward the m-line
At the end of the power stroke, the ADP is released, and the
cycle can begin anew
Note:
Each cross-bridge undergoes its own cycle, independently of the
others (ie cross bridges movement is not synchronized)
At any one time perhaps only 50% of the cross-bridges in a
contracting filament are bound and producing movement.
3] ATP performs two distinct roles:
a] Hydrolysis of ATP provides energy for cross-bridge movement
b] Initial binding of ATP to myosin breaks the myosin-actin bond
An aside on rigor mortis - after death, the concentration of ATP in all
cells (including muscle cells) begins to decline because ATP is no longer
created by metabolism.
-metabolism shuts down (no more gas exchange)
-without a good supply of ATP, actin and myosin remain bound together
tightly. (this is the cause of rigor mortis)
-later, the muscles relax because of tissue degradation
-this clue, along with body temperature and others, allows forensic
doctors to determine time of death fairly accurately
4] The role of Troponin and Tropomyosin
a] Troponin and Tropomyosin are two regulatory proteins that prevent
the interaction of myosin and actin in a resting muscle fiber.
At rest, these proteins work together to prevent cross bridges
from binding actin.
b] Tropomyosin covers the binding sites on the cross bridges, and is
held in place by troponin
5] The role of Calcium...how does the muscle activate for contraction?
F 11-16
a] Electrical events in the plasma membrane cause the release of Ca+
in the cell; Voltage-gated channels in ER opened
b] Calcium binds to troponin, and causes a shift in conformation,
which uncovers the cross-bridge binding sites (moves tropomyosin out of the way)
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How does the nervous system cause a muscle to contract? Table 11-2
This process is referred to as "excitation-contraction coupling"
1] The process begins with a signal from the CNS in the form of action
potentials that travel down the axon of a motor neuron (AKA "somatic efferent
neuron")
2] The axon of a motor neuron divides up into many branches, each of
which innervates a single muscle fiber.
A motor neuron plus all of the fibers it innervates is called a
motor unit
3] Each of these branches forms a synapse with a special region of the
muscle fiber plasma membrane known as the motor end plate
The junction of the axon terminal and the motor end plate is called
the neuromuscular junction F 11-18, 19
4] Just as in a normal synapse, the the axon terminal has vesicles full
of neurotransmitter - in this case, acetylcholine (ACh) - and much more
than encountered in a normal synapse.
Table expanded:
1) An AP arrives at the axon terminal and depolarizes it
2) Voltage sensitive calcium channels open, allowing calcium to
diffuse into the axon terminal.
3) Increased calcium causes exocytosis of the vesicles containing
ACh, which is then released into the cleft.
4) ACh binds to ACh receptors on the motor end plate, which open and
are permeable to Na+ and K+ ions, producing a local potential - the
end-plate potential, (EPP).
5) Unlike a normal synapse, the amount of Ach released is HUGE, and
therefore a single AP in the motor neuron can depolarize the motor end
plate to threshold.
6) The plasma membrane of a muscle fiber is an excitable membrane,
which is capable of generating and propagating action potentials.
7) The EPP surpasses threshold and triggers an AP that propagates
through the muscle fiber plasma membrane (most end plates are in
approximately the center of a muscle fiber, thus the AP is propagated in
two directions out toward the end of the fiber.
8) The AP is transmitted to all of the myofibrils on the interior of
a fiber by a network of tubes called Transverse tubules (or, T-tubules)
-the transverse tubules pass through a layer of membraneous material
called the Sarcoplasmic reticulum that surrounds each myofibril (i.e. the
myofibrils are embedded in the SR)
-SR is modified endoplasmic reticulum, with high Ca+.
9) The passage of APs through the T-tubules triggers the opening of
calcium channels in the SR, which releases Ca+ into the cytosol which
contains the myofibrils.
10) Ca+ binds to troponin in the myofibrils, and causes the
initiation of contraction.
11) Ca+ release stops when the high cytosolic Ca+ closes the SR
channels.
-as the concentration of calcium increases, more of these binding sites
become occupied by Ca+ and the release of calcium is halted.
12) Contraction will not cease until Ca+ is removed from troponin
-this is accomplished by lowering the cytosolic concentration of Ca+ by
using Ca-ATPase pumps that actively transport calcium back into the SR,
and effectively allow the muscle to relax
13) AChE degrades ACh - stimulus removed; repolarization to resting
state
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Skeletal Muscle Energy Requirements F 11-26
Muscles require high levels of available ATP
1] At rest, most of the E obtained from aerobic resp of fatty acids
(from plasma and muscle triglycerides)
2] Stored glycogen may be hydrolysed to provide glucose for glycolysis
and oxidative phosphorylation - effective for 1st 5-10 min of
exercise
3] Glucose transported from plasma provides sustained source - aerobic
and anaerobic pathways
4] Unique option: phosphorylation of ADP with Pi from creatine phosphate
by creatine phosphokinase
-provides early spurt before glycolysis kicks in
-provides ATP for long term exercise (super efficient)
-cardiac muscle has different isozyme
Other designations of skeletal muscle fibers
1] fibers can be classified as:
- fast or slow, based on contraction time; depends on myosin ATPase
activity
- red or white, red (sk and cardiac) have myoglobin, white do not
- oxidative or glycolytic
2] Three major types:
- Slow-oxidative fibers (Type I)
- Fast-oxidative fibers (Type IIa)
- Fast-glycolytic fibers (Type IIb)
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Skeletal Muscle and Work
Contraction of muscles generates tension. This permits muscles to shorten
and to perform mechanical work.
The contraction strength must overcome the load on that muscle for it to
shorten.
Mechanics of Single Fiber Contraction
General terminology:
Tension: the force produced by a contracting muscle
Load: the force exerted on a muscle by the weight of an object
Lengthening Contraction: when an unsupported load > tension, the load is
pulling / stretching the muscle despite the action of the cross-bridges.
-this type of "contraction" is the result of external forces acting
on the muscle, NOT any molecular mechanism that results in muscle
lengthening per se
Twitch Contraction: the mechanical response of a muscle fiber to a single
action potential.
Chain of events in a twitch: F11-20
1) an action potential arrives at the fiber and elicits a response -
the twitch
2) Latent Period - time required for excitation-contraction coupling
a few millisecond delay before tension in the muscle fiber begins
to increase
3) Contraction time - the muscle begins to contract, and it takes some
time to reach peak twitch tension. Dependent of presence of Ca++
e.g. fast fibers as short as 10 ms; slow fibers as long as 100 ms
4) Relaxation - as calcium is pumped back into the SR, the muscle
slowly relaxes, and tension falls off slowly.
Frequency-Tension Relationship: F11-24
In a single twitch, the muscle fiber is stimulated with a single AP
[AP lasts only 1 to 2 ms]
A twitch lasts 10-100 ms, therefore, many APs can arrive at a muscle
fiber before a single twitch is complete.
Summation - the activity of a fiber in response to many APs
-is the increase in mechanical response of a muscle
in response to successive action potentials.
Tetanus - a continuous contraction that occurs when a fiber is repeatedly
stimulated at a frequency that is too high to allow muscle relaxation
If we continue to increase the frequency of stimulation, the continuous
tension generated in the muscle will rise to a peak and will plateau
at the maximal tetanic tension
WHY is the maximal tetanic tension greater than the tension generated by
any single twitch?
1) muscles contain elastic elements that must be stretched to increase
tension
2) a single action potential saturates all the troponin with calcium
making all of the cross-bridges available for the generation of maximal
force, however, by the time the elastic elements are stretched, the
Ca-ATPase pumps have already depleted the calcium supply, thus
inactivating some of the cross-bridges.
.
In a tetanic contraction, the successive APs, cause calcium to be
released continuously, so the calcium supply is not depleted, allowing
maximal tetanic tension to be achieved.
Fatigue: decline in muscle tension after extended period of contaction
Imbalance of ions prevents normal transmission of AP
Length - Tension Relationship. F11-25
The amount of tension a muscle can generate changes in relation to its
length
The length at which maximal tension is generated is termed the Optimal
Length (lo)
The length-tension relationship is mainly due to the degree of overlap
between thick and thin filaments.
Extremes:
as the muscle shortens, the actin filaments begin to overlap and
interfere with binding of myosin in a way that would generate force
as the muscle fiber lengthens, actin and myosin overlap declines
until the two can no longer overlap, and no force is generated.
Optimum: near Optimal Length (lo), there is maximal clear overlap
between actin and myosin filaments, and therefore maximal force
may be generated.
Smooth muscles - involuntary
Found in many systems (GI tract, circulatory systems, skin, urinary
bladder
Appearance different from skeletal muscle F11-35, 37
Cells are smaller with tapered ends; single nucleus
Often gap junction coupled
Myosin and actin present but not organized into sarcomeres - lack
striations
Actin anchored to either cell membrane or cytoplasmic dense bodies
(functionally equivalent to Z-line) same sliding filament
mechanism is in operation.
More complex activation stimuli -
complex membrane potentials, slow waves/pacemakers
Smooth muscle contraction (in vertebrates);
Autonomic nervous system signals muscle to contract
Contraction is still linked to increases in calcium ion concentration
BUT no SR, troponin or tropomyosin
Instead a cascade of reactions that activate kinase
Myosin crossbridges are only activated when they are "phosphorylated"
Kinase uses ATP for this
The crossbridges then bind to actin and initiate contraction.
Duration of contraction is much longer, variable tension
Length-tension relationship more extended
good property because many organs need to contract over a broad range
of muscle
cell extension (e.g uterus, urinary bladder)
Neurotransmitters may increase or decrease sm. mus. tension
Chemical signals in the local environment may also serve as regulators
Cardiac (Heart) muscle
Found only in the heart, a hybrid of smooth and skeletal characteristics
Similar to skeletal, with the following major exceptions:
Not multinucleate
Electrically coupled via gap junctions at intercalated disks - permits
unified activity
Behaves as single functional myocardial unit - no graded response
Myocardial units: atria, ventricles
Responds to multiple neurotransmitters and hormones
Slower APs and longer tension times
Some fibers generate pacemaker potentials, part of the conducting system
Receive inhibitory inputs