Download Lecture Notes Part 4 Muscle Energetics

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LECTURE NOTES
MUSCLE PHYSIOLOGY PART 4
Physiology of Skeletal Muscle Fibers
For skeletal muscles to contract:
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The fiber must be stimulated by a nerve ending
An action potential must be generated along the sarcolemma
The action potential must be propagated along the sarcolemma
Intracellular calcium must rise to trigger contraction
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THE NEUROMUSCULAR JUNCTION
The neuromuscular junction is a connection between an axon terminal
and a muscle fiber where stimulation of the muscle cell to contract
occurs.
The neuromuscular junction consists of the plasma membrane of the
motor neuron axon terminal, the synaptic cleft, and the motor endplate.
The motor endplate is part of the sarcolemma where chemically
regulated ion channels that respond to neural stimulation are found.
Junctional folds increase the surface area at the motor endplate.
A nerve impulse causes the release of acetylcholine to the synaptic cleft,
which binds to receptors on the motor end plate, triggering a series of
electrical events on the sarcolemma.
An action potential, or wave of depolarization of significant strength,
opens voltage regulated Ca++ channels in the axon terminal.
Ca++ influx into the axon stimulates fusion of synaptic vesicles with the
axon terminal plasma membrane and the release of neurotransmitter
(Ach) in the synaptic cleft.
Ach diffuses across the synaptic cleft, binds to receptors on the motor
endplate, and opens chemically-regulated ion channels in the
sarcolemma.
Ach is broken down by acetylcholine esterase, which terminates
stimulation of the sarcolemma
https://www.youtube.com/watch?v=7wM5_aUn2qs
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When acetylcholine binding with receptors opens chemically-regulated
ion channels in the sarcolemma Na+ ions enter the cell faster than K+
ions exit, which makes the membrane potential slightly less negative
(depolarizes the membrane) This is an end plate potential.
Positively charged ions move across the inside of the sarcolemma into
more negative areas - this is a wave of depolarization. The
depolarization can be measured (just like a resting membrane potential)
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and is referred to as a graded local potential, or in this specific case, an
endplate potential.
Generation of an action potential across the sarcolemma occurs in
response to the wave of depolarization reaching a voltage regulated Na+
channel with sufficient strength to open it.
The degree of depolarization required to open a voltage regulated
Na+ channel is called threshold (typically 15 - 20 mV above the resting
membrane potential).
The influx of Na+ through voltage regulated channels opens voltage
regulated K+ channels.
As K+ leaves the cell it becomes repolarized and can be stimulated
again.
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EXCITATION-CONTRACTION COUPLING
Excitation-contraction coupling is the sequence of events by which an
action potential on the sarcolemma results in the sliding of the
myofilaments.
Ionic calcium in muscle contraction is kept at almost undetectable levels
within the cell through the regulatory action of intracellular proteins.
Muscle fiber contraction follows exposure of the myosin binding sites,
and follows a series of events.
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Excitation - Contraction Coupling
Film: Excitation contraction coupling
https://www.youtube.com/watch?v=HJj3jUVDFFo
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Contraction of a Skeletal Muscle
A motor unit consists of a motor neuron and all the muscle
fibers it innervates. It is smaller in muscles that exhibit fine
control.
The muscle twitch is the response of a muscle to a single action
potential on its motor neuron. Note the latent period, the period of
contraction, and the period of relaxation on the myogram.
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GRADED MUSCLE RESPONSES
There are three kinds of graded muscle responses: wave summation,
multiple motor unit summation (recruitment), and treppe.
Wave summation is generated by increasing the frequency of the
stimulus.
Multiple motor unit summation or recruitment is generated by increasing
the strength of the stimulus (increasing the number of motor neurons
firing).
Treppe is its own thing - the response occurs with the frequency and
strength of stimulus held constant.
Muscle Response to Increased Frequency of Stimulation: Wave
Summation
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Muscle Response to Stronger Stimuli: Multiple Motor Unit
Summation (Recruitment)
Recruitment of Motor Neurons: The Size Principle
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Treppe
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Muscle tone is the phenomenon of muscles exhibiting slight
contraction, even when at rest, which keeps muscles firm,
healthy, and ready to respond.
Isotonic contractions result in movement occurring at the joint
and a change in the length of muscles (the force remains
constant).
Concentric isotonic contractions - The
muscle shortens as it moves the load
Eccentric isotonic contractions - The
muslce lengthens as it resists the load
Isometric contractions result in increases in muscle tension,
but no lengthening or shortening of the muscle occurs.
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Film: isotonic vs isometric
https://www.youtube.com/watch?v=pbXML3m2hSE
https://www.youtube.com/watch?v=PHTUlwCnCe8
Muscle Metabolism
Energetics of Muscle Contraction
Sources of Energy for Muscle Contraction
 Energy is needed for
1. Cross-bridge pulling actin
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2. To pump calcium from the sarcoplasm to the sarcoplasmic reticulum after
contraction
3. Pumping sodium-potassium
Concentration of ATP in the muscle fiber sufficient to maintain contraction for only 1 to
2 seconds
ATP is split to form ADP which transfers the energy from the ATP to the contracting
machinery
ADP is rephosphorylated to form new ATP
Three sources of energy for rephosphorylation
1. Phosphocreatine- similar to ATP
2. Glycolysis of glycogen stored in muscle
 Breakdown to pyruvic acid and lactic acid
 Can occur without oxygen (anaerobic)
3. Oxidative metabolism
 More than 95% of all energy used by the muscles for sustained, longterm contraction is derived by this mechanism
https://www.youtube.com/watch?v=UIR2VFdFhMo
Muscles contain very little stored ATP, and consumed ATP is
replenished rapidly through phosphorylation by creatine
phosphate, glycolysis and anaerobic respiration, and aerobic
respiration.
Muscles will function aerobically as long as there is adequate
oxygen, but when exercise demands exceed the ability of
muscle metabolism to keep up with ATP demand,
metabolism converts to anaerobic glycolysis.
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Muscle fatigue is the physiological inability to contract due to
the shortage of available ATP.
Oxygen debt is the extra oxygen needed to replenish oxygen
reserves, glycogen stores, ATP and creatine phosphate
reserves, as well as conversion of lactic acid to pyruvic acid
glucose after vigorous muscle activity.
Heat production during muscle activity is considerable. It
requires release of excess heat through homeostatic
mechanisms such as sweating and radiation from the skin.
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Force of Muscle Contraction
As the number of muscle fibers stimulated increases, force of
contraction increases.
Large muscle fibers generate more force than smaller muscle
fibers.
As the rate of stimulation increases, contractions sum up,
ultimately producing tetanus and generating more force.
There is an optimal length-tension relationship when the
muscle is slightly stretched and there is slight overlap
between the myofibrils.
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Velocity and Duration of Contraction
There are three muscle fiber types: slow oxidative fibers, fast
oxidative fibers, and fast glycolytic fibers.
Muscle fiber type is a genetically determined trait, with
varying percentages of each fiber type in every muscle,
determined by specific function of a given muscle.
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As load increases, the slower the velocity and shorter the
duration of contraction.
Recruitment of additional motor units increases velocity and
duration of contraction.
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Adaptations to Exercise
Aerobic, or endurance, exercise promotes an increase in capillary
penetration, the number of mitochondria, and increased synthesis of
myoglobin, leading to more efficient metabolism, but no hypertrophy.
Resistance exercise, such as weight lifting or isometric exercise,
promotes an increase in the number of mitochondria, myofilaments and
myofibrils, and glycogen storage, leading to hypertrophied cells.
Types of Skeletal Muscle Contractions
Characteristics of Whole Muscle Contraction

Isometric & Isotonic Contractions
o Isometric
 When muscle does not shorten during contraction
 Isometric Contractions: Tension but no shortening of the muscle occurs.
Energy is still used!
 Isometric contractions generate force without changing the length of the
muscle
 Example: contractions that serve to keep the body fixed in position as in
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1. maintaining posture,
2. maintaining balance,
3. fixing a proximal joint so a distal joint may move,
4. Maintaining muscle tone.
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o
Isotonic
 When muscles shorten during contraction but tension on the muscle remains
constant throughout the contraction
 Tension produced and overall shortening of the muscle as a load is moved
through the range of motion of the joint.
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Isotonic contractions serve to bring about movement or change in body
position. Example = flexion, extension, adduction, abduction, etc.
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Isotonic contractions generate force by changing the length of the
muscle and can be concentric contractions or eccentric contractions.
 A concentric contraction causes muscles to shorten, thereby
generating force.
o Concentric (Of a motion), in the direction of
contraction of a muscle. (E.g., extension of the lower
arm via the elbow joint while contracting the triceps
and other elbow extensor muscles
 Eccentric contractions cause muscles to elongate in response to
a greater opposing force.
o Eccentric --Against or in the opposite direction of
contraction of a muscle. (E.g., flexion of the lower arm
(bending of the elbow joint) by an external force while
contracting the triceps and other elbow extensor
muscles to control that movement.
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 Most body activities involve both isotonic and isometric contractions.
https://www.youtube.com/watch?v=pbXML3m2hSE
https://www.youtube.com/watch?v=PHTUlwCnCe8
Fast vs Slow Muscle Fibers
Every muscle of the body is composed of a mixture of fast and slow muscle fibers
Slow Fibers (Type 1, Red Muscle)
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Smaller than fast fibers
Have more extensive blood vessel system and more capillaries to supply extra amounts of
oxygen
Have great numbers of mitochondria to support high levels of oxidative metabolism
Respond more slowly but with prolonged contraction
Contain large amounts of myoglobin, an iron containing protein. It combines with oxygen
and stores it until needed (greatly speeds oxygen transport to the mitochondria. Gives the
muscle a red appearance
Example: soleus
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Fast Fibers (Type 2, white muscle)
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Muscles that react rapidly
Large for great strength of contraction
Extensive sarcoplasmic reticulum for rapid release of calcium ions to initiate contraction
Presence of large amounts of glycolytic enzymes for rapid release of energy by the glycolytic
process
Have less extensive blood supply because oxidative metabolism is of secondary importance
Have fewer mitochondria.
Deficient in myoglobin gives it white appearance
Example: anterior tibialis
https://www.youtube.com/watch?v=HpyRkoL42w0
https://www.youtube.com/watch?v=l5yMz2lFgx0
Mechanics of skeletal muscle contraction
Motor Unit—all the muscle fibers innervated by a single nerve fiber
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Each motor neuron that leaves the spinal cord innervates multiple muscle fibers
All the muscle fibers innervated by a single nerve fiber are called a motor unit
Small muscles that react rapidly and whose control must be exact have more nerve fibers
Muscle Contractions of Different Force—Force Summation
Muscle twitch
o
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Twitch: A single isotonic response as a result of a single threshold (liminal) stimulus.
(This is not the type of twitch you feel in your body due to being tired or a chemical
imbalance).
The muscle contracts quickly and then relaxes. A twitch can be demonstrated with an
instrument that produces a myogram---a tracing of a muscle contraction or activity
https://www.youtube.com/watch?v=3191s4-TZRo
This cycle by which the myosin heads become energized, form an attachment, swivel and
then detach is repeated many times in all the sarcomeres of all the myofibrils within the cell. The net
effect of all this molecular movement is muscle contraction!
Role of Calcium
.
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The calcium ion (Ca++) plays a key role in determining when contraction occurs
Ca++ is concentrated in smooth endoplasmic reticulum called sarcoplasmic reticulum which
surrounds the myofibrils like the sleeve of a very loose knit sweater might surround your arm. When a
nerve impulse arrives at the muscle cell, the impulse to contract spreads throughout the skeletal
muscle cell and causes channels in the membrane of the sarcoplasmic reticulum to open. This causes
the Ca++ to rush out of the sarcoplasmic reticulum down its concentration gradient.
Ca++ attaches to a protein called tropomyosin that covers the attachment site on the actin
myofilaments. This causes the tropomyosin to uncover the attachment site which permits the myosin
head to bind to the attachment site and begin the cycle described above. As long as the
Ca++ concentration remains high cycling, or contraction, continues.
Skeletal Muscle Contraction
Contraction of a skeletal muscle as a whole depends upon the contraction of individual skeletal
muscle cells. An individual skeletal muscle cell will either contract or not contract if it is stimulated.
This is referred to as the “all or none” response. However, because each muscle consists of a number
of individual muscle cells, the contraction of whole muscles can vary.
The different degree of contraction that can occur in a whole muscle results in graded responses to
different degrees of stimuli. Graded responses are achieved in two ways:
1) Changing the frequency of stimulation;
2) Changing the number of muscle cells stimulated to contract.
Tetanus
Contractions of skeletal muscles result from the impulses delivered to them by nerves. The
impulses normally are normally delivered at a high frequency and results in the phenomenon
called tetanus.
If only a single impulse or stimulus is delivered to a muscle a contraction occurs and is quickly
followed by relaxation of the muscle. This is called a muscle twitch. If many impulses or stimuli are
delivered to the muscle the muscle contracts but does not have time to relax before it contracts again.
This is called tetanus. If the frequency of stimulation permits the muscle to relax to an even slight
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degree between contractions, the tetanus is unfused or incomplete. If the frequency is so high that
relaxation does not occur during contraction, the tetanus is fused or complete (see Fig. 6.9).
Our ability to produce smooth and sustained movements when we use our muscles in the result of
tetanus.
Muscle Fiber Excitation
The events already described (calcium entry, cross-bridge cycling)
occur when a muscle fiber is excited to fire an action potential. An
action potential is triggered in a muscle fiber when it is depolarized
due to excitation at its synapse, the neuromuscular junction.
Each muscle fiber has one neuromuscular junction, receiving input
from just one somatic efferent neuron. An action potential in a
somatic efferent neuron causes it to release the
neurotransmitter acetylcholine (ACh). ACh binds to nicotinic
receptors in a specialized region of the muscle fiber known as
the motor endplate. ACh binding allows Na+ ions to enter the cell,
causing a depolarizing excitatory postsynaptic potential (EPSP)
that is above threshold and triggers an action potential.
The neuromuscular junction differs from typical synapses in the CNS
in one critical way: the EPSP is always well above threshold. This
means that under normal circumstances, an action potential in a
somatic efferent neuron always elicits an action potential in the
muscle fiber.
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The figure shows a muscle cell EPSP in response to a single action
potential in a somatic efferent neuron. Such a recording is made by
blocking voltage-gated Na+ channels; this prevents the muscle
action potential from occuring so that one sees just the EPSP. The
dotted red line shows the threshold. The amount of ACh released
with one neuronal action potential is enough to depolarize the
muscle fiber well above the threshold for eliciting an action
potential. The degree that the EPSP exceeds threshold is known as
the safety factor.
In the autoimmune disorder myasthenia gravis, antibodies to the
acetylcholine receptor reduce the number of functioning receptors at
the motor endplate, decreasing the size of the EPSP and reducing
the safety factor. Patients with this disorder have muscle weakness
because somatic efferent neurons are less able to excite muscle
cells.
Myasthenia gravis can be diagnosed using
the electromyogram (EMG). The electromyogram is an
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extracellular recording of the electrical activity of motor units.
A motor unit consists of a somatic efferent neuron and all the
muscle fibers that it innervates. In the electromyogram, one records
a potential known as the compound action potential, which is the
summed action potentials of all the muscle fibers in the motor unit.
To diagnose myasthenia gravis, the compound action potential is
measured in response to repetitive nerve stimulation. Repetitive
stimulation of the nerve depletes ACh in the presynaptic terminal,
causing a decrease in the amplitude of the EPSP. Normally, because
of the high safety factor, EPSPs are still well above threshold to
elicit an action potential. Therefore, repeated stimulation causes no
change in the compound action potential because the somatic
efferent neuron still excites every muscle fiber in the motor unit
(left recording).
In myasthenia gravis, this slight decrease in ACh release can cause
some EPSPs to fall below threshold, so some of the muscle fibers in
the motor unit fail to fire action potentials. One sees a decline in the
amplitude of the compound action potential with repeated
stimulation (recording on the right) because fewer muscle fibers in
the motor unit are firing action potentials.
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Myasthenia gravis is treated with acetylcholinesterase inhibitors.
The goal is to increase the amount of acetylcholine to promote
excitation at the synapse.
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Now, test your grasp of these concepts with the muscle quiz.
Quick Quiz: Skeletal Muscle Cell
Biology
Fill-in Answer
Correct False
Correct Answer
1. Name the two proteins that interact to
generate force.
2. Which part of the myosin molecule forms
the cross-bridge?
3. Rigor mortis occurs due to a lack of
__________.
4. Does ATP hydrolysis occur before or after
myosin binds to actin?
5. Name the regulatory protein in skeletal
muscle that binds calcium ions.
6. Name the regulatory protein that blocks
myosin binding sites on the actin filament.
7. What is the source of the Ca++ that
regulates skeletal muscle cross-bridge
cycling?
8. The membrane of the T-tubules is
continuous with the _______.
9. What interacts with the "foot" to open the
sarcoplasmic reticulum Ca++ channel?
10. The activity of which protein leads to
skeletal muscle relaxation?
11. The safety factor is a function of the
amplitude of the __________.
12. What autoimmune disorder decreases
the safety factor?
13. In the above disorder, the patient makes
antibodies against which protein?
(Spelling must be
correct)
Quick Quiz: Skeletal Muscle Cell
Biology
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Fill-in Answer
1. Name the two proteins that interact to
generate force.
2. Which part of the myosin molecule forms
the cross-bridge?
3. Rigor mortis occurs due to a lack of
__________.
4. Does ATP hydrolysis occur before or after
myosin binds to actin?
5. Name the regulatory protein in skeletal
muscle that binds calcium ions.
6. Name the regulatory protein that blocks
myosin binding sites on the actin filament.
7. What is the source of the Ca++ that
regulates skeletal muscle cross-bridge
cycling?
8. The membrane of the T-tubules is
continuous with the _______.
9. What interacts with the "foot" to open the
sarcoplasmic reticulum Ca++ channel?
10. The activity of which protein leads to
skeletal muscle relaxation?
11. The safety factor is a function of the
amplitude of the __________.
12. What autoimmune disorder decreases
the safety factor?
13. In the above disorder, the patient makes
antibodies against which protein?
Correct False
Correct Answer
myosin and actin
head domain
ATP
before
troponin
tropomyosin
sarcoplasmic reticulum
sarcolemma
T tubulesensor
Ca++-ATPase
ESP in muscle cell
myasthenia gravis
acetylcholine receptor
(Spelling must be
correct)