MECHANICS OF SKELETAL MUSCLE Dr. Ayisha Qureshi Assistant
Professor MBBS, MPhil
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A MUSCLE TWITCH
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The Muscle Twitch Muscle twitch. A single action potential
causes a brief contraction followed by relaxation in the muscle.
This is called a single Muscle twitch. Electrical and mechanical
events in a muscle always occur in relation to one another: The
electrical event (Action potential) is followed by the mechanical
events (contraction). The whole process is called
Excitation-contraction coupling. Twitch starts 2 ms after
depolarization of the membrane, before repolarization is
complete----- Why the delay?
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Contractile activity and electrical activity in skeletal
muscle: A single action potential in a skeletal muscle fiber lasts
only 1 to 2 msec, while a skeletal muscle contraction and
relaxation lasts for about 100 msec. The onset of the resulting
contractile response lags behind the action potential because the
entire excitationcontraction coupling must occur before cross-
bridge activity begins. In fact, the action potential is completed
before the contraction even begins. Time is take for the following
processes: AP to spread down the t-tubule. Release of Ca 2+ Ca 2+
to attach to Troponin C Power stroke Ca 2+ uptake by the ATPase
pump in the SR.
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LENGTH & TENSION RELATIONSHIP:
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Length & Tension Relationship A relationship exists between
the length of the muscle before the onset of contraction and the
tension (force developed in the muscle) that each contracting fiber
can develop at that length. For every muscle there is an optimal
length (lo) at which maximal force can be achieved on a subsequent
contraction. More tension can be achieved when beginning at the
optimal muscle length than when the contraction begins with the
muscle less than or greater than its optimal length. This
lengthtension relationship can be explained by the sliding filament
mechanism of muscle contraction.
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Length & Tension relationship Length (L) and Force (F) or
tension of a muscle are closely related: 1.Optimal length (lo): (In
the previous slide seen as point A) This is the point where thin
filaments optimally overlap the thick filaments. This is also the
normal length of the sarcomere. At this point, maximal no. of
cross-bridges & actin filaments are accessible to each other
for binding & bending. 2.At lengths greater than Optimal length
(lo): (in the previous slide seen as point C) This is when the
muscle is passively stretched. The thin filaments are pulled out
from between the thick filaments, decreasing the number of actin
sites available for cross- bridge binding. So some of the
cross-bridge and actin sites do not match up and go unused. So, NO
actin myosin overlap, tension developed by the muscle is zero. 3.At
lengths less than Optimal length (lo): (in the previous slide seen
as point D) If a muscle is shorter less tension is developed for
the following reasons: - The thin filaments from the opposite sides
become overlapped. - The ends of the filament become forced against
the z-discs so no further shortening can take place.
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Length-Tension Relationship Points to Remember: 1.When the
muscle is at its Optimal length, it contracts with the maximum
tension. 2. Force of contraction (tension generated) is maximal at
the resting (Optimal) length & decreases if the muscle is
longer or shorter.
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ENERGETICS OF MUSCLE CONTRACTION:
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Energy sources ATP. : The main source of energy for muscle
contraction is ATP. ATP is used in 3 different steps in
contraction-relaxation process. These steps are: 1.Splitting of ATP
by myosin ATPase provides the energy for the power stroke of the
cross bridge. 2. Binding (but not splitting) of a fresh molecule of
ATP to myosin lets the bridge detach from the actin filament at the
end of a power stroke so that the cycle can be repeated. This ATP
is later split to provide energy for the next stroke of the cross
bridge. 3.Active transport of Ca 2+ back into the sarcoplasmic
reticulum during relaxation depends on energy derived from the
breakdown of ATP and is used by the ATP- dependant Calcium Pump.
The concentration of ATP in a Muscle fiber= 4mmole. It is
sufficient to maintain full contraction for only 1 to 2 seconds at
most.
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SOURCES OF ATP There are 3 main sources of ATP: 1.Creatine
Phosphate/ Phosphagen Energy system: - takes place within the
muscle -uses the Phosphate bond from Creatine phosphate - First
source of ATP when exercise begins; instantaneous energy available.
- short bursts of high-intensity exercise. E.g. high jump, sprints
2. Oxidative phosphorylation: aerobic or endurance type exercise. -
takes place in the mitochondria - requires oxygen & uses fatty
acids, glucose in blood and glycogen stores - to sustain long
duration mild to moderate aerobic exercise. E.g. walks, jogging,
swimming, marathon runners. 3. Glycolysis: anaerobic or
high-intensity exercise - when oxygen demands are not met &
oxygen NOT available. - uses glycogen stores of the muscle -
proceeds very rapidly and leads to formation of lactic acid. -
moderate to severe exercise. E.g. 800 meter run. Cannot be
sustained for long time.
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CHARACTERISTICS/ PROPERTIES OF WHOLE MUSCLE CONTRACTION : We
have been talking about muscle fibers as a single muscle cell.. Now
we will consider Muscle as a whole consisting of several to several
hundred muscle fibers.
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1. MUSCLE FATIGUE Definition: Fatigue occurs when prolonged
& strong stimulation of an exercising muscle reaches a stage
when the muscle is no longer able to respond to the stimulation
with the same degree of contractile activity. Is of 2 main types:
1.Muscle fatigue: occurs in the muscle & is a defense mechanism
that protects the muscle by preventing it from reaching a point
where no ATP will be available. 2.Central fatigue: more
psychological. Occurs when CNS no longer activates the motor
neurons supplying the muscles. Person stops exercising even though
the muscles can still perform.
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1. MUSCLE FATIGUE CAUSES: 1.Depletion of Glycogen energy
stores. 2.Accumulation of Hydrogen ions from lactic acid- interfere
with cross- bridge functions. 3.Intracellular acidosis from lactic
acid inhibits glycolysis enzymes & slows ATP production. 4.NT
depletion at the NMJ. 5.Central fatigue- lack of will & sleep.
6.Accumulation of extracellular K +
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2. OXYGEN DEBT 2 liters The body normally contains about 2
liters of oxygen: 0.5 liters Air in lungs 0.25 liters Body Fluids 1
liter Hb of Blood 0.3 liters Muscle with Myoglobin
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2. OXYGEN DEBT During muscular exercise, a lot more Oxygen is
supplied to the muscle than is present. O 2 consumption = energy
expended All stored O 2 is used within a minute or so After
exercise is over: 2 liters of normally present blood must be
replenished 9 liters extra must be provided for: 1)Resynthesis of
the Creatine Phosphate. 2)Conversion of lactate into pyruvate.
3)Form fresh supplies of ATP through oxidative
phosphorylation.
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2. OXYGEN DEBT All this extra Oxygen that must be repaid
(11.5liters) to the body is called the Oxygen Debt. SO, A person
must breathe rapidly even after the exercise is over!
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3. MUSCLE TONE Even when muscles are at rest, a certain amount
of tautness usually remainsThis is called Muscle Tone. Cause: Low
rate of nerve impulses coming from the spinal cord which are
controlled by the: 1.Signals from the brain to the spinal cord-
anterior motor neurons 2.Signals that originate in the muscle
spindles located in the muscle itself-Intrafusal fibers
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4. MOTOR UNIT Definition: All the muscle fibers innervated by a
single nerve fiber are called a MOTOR UNIT. OR Each single motor
neuron plus all the muscle fibers it innervates is called a MOTOR
UNIT. One motor neuron innervates a number of muscle fibers, but
each muscle fiber is supplied by only one motor neuron. When this
neuron is stimulated, all the muscle fibers supplied by it contract
together. Each muscle consists of a number of mixed motor units.
For a weak contraction of the whole muscle, only one or a few of
its motor units are activated. The number of muscle fibers per
motor unit and the number of motor units per muscle vary widely,
depending on the specific function of the muscle. E.g. the kind of
work that the muscle performs..
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4. MOTOR UNIT Number of muscle fibers in a motor unit vary in
different muscles from 2 or 3 to more than 1000. Average: 80-100
muscle fibers to a motor unit. Muscles which have to perform fine
grade, intricate movements have motor units with as few as 3-5
muscle fibers to a unit.e.g. hand, eye Muscles with relatively
crude movements, number of muscle fibers is quite large. E.g.
muscles of lower limbs In one whole muscle, different motor units
overlap
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5. ALL OR NONE LAW In a single muscle fiber exactly the same as
in the single nerve fiber. A sub-threshold stimulus does not
produce a response while a threshold or supra-threshold stimulus
produces a maximal response. In whole muscle the response is
different. A gradual in stimulus strength causes a gradual in
muscle contraction till a maximum is obtained. This is because with
each in stimulus strength more & more motor units are
stimulated. When all motor units are activated---all muscle fibers
are contracted, then a further in the strength of the stimulus is
without any additional contractile effect.
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6. Force of Contraction Summation: Summation: is the process of
adding together of individual twitch contractions to increase the
intensity of whole muscle contraction. There are 2 types of
summation: 1.Multiple Fiber Summation (No. of motor units
stimulated) 2.Frequency Summation
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6. a: Multiple Fiber Summation Definition: It is the summation
of individual muscle fiber contractions by increasing the number of
motor units contracting simultaneously. Initially, with a weak
signal from the CNS-only smaller units are stimulated. Later, when
signal from CNS becomes stronger, larger motor units are
excited----This is called SIZE PRINCIPLE. Importance: It allows
gradation of force to occur for weak & strong contractions.
Cause: Smaller motor units are driven by smaller motor nerves &
are more excitable than large ones---so are excited first! Then, if
greater strength is required, then larger motor units are
recruited.
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6. b: FREQUENCY SUMMATION Definitions: Force of contraction
increases by increasing the frequency of contractions. Two twitches
from 2 action potentials add together to produce greater tension in
the fiber than produced by a single action potential. This is
called twitch summation or frequency summation. Force generated by
the contraction of a single muscle fiber can be by increasing the
rate at which the action potentials stimulate the muscle fiber. If
repeated APs are separated by long intervals of time, muscle fibers
have time to relax completely between stimuli. If interval of time
between AP shortened, the Muscle fiber will not have relaxed
completely at time of 2 nd stimulus, resulting in a more forceful
contraction.
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A single action potential in a muscle fiber produces only a
twitch. Let us see what happens when a second action potential
occurs in a muscle fiber. If the muscle fiber has completely
relaxed before the next action potential takes place, a second
twitch of the same magnitude as the first occurs. The same
excitation- contraction events take place each time, resulting in
identical twitch responses. If, however, the muscle fiber is
stimulated a second time before it has completely relaxed from the
first twitch, a second action potential causes a second contractile
response, which is added piggyback on top of the first twitch.
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FREQUENCY SUMMATION When APs come one after the other after the
relaxation of the muscle is complete. When APs come one after the
other before relaxation of the muscle is complete
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6. b: FREQUENCY SUMMATION If APs continue to stimulate the
muscle repeatedly at short intervals, there is no time for complete
relaxation between contractions Individual twitches fuse into one
continuous contraction Whole muscle contraction appears to be
smooth, sustained & of maximal strength This is called
TETANIZATION or TETANUS (A tetanic contraction is usually three to
four times stronger than a single twitch.)
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Physiologic basis of twitch summation & Tetanus: The main
reason is the sustained elevation in cytosolic Ca 2+ permitting
greater cross-bridge cycling. As the frequency of action potentials
increases, the duration of elevated cytosolic Ca 2+ concentration
increases, and contractile activity likewise increases until a
maximum tetanic contraction is reached. With tetanus, the maximum
number of cross-bridge binding sites remain uncovered so that
cross-bridge cycling, and consequently tension development, is at
its peak.
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6.b: FREQUENCY SUMMATION & TETANUS Two types of Tetanus:
1.COMPLETE or FUSED TETANUS: If repeated stimuli are applied at
fast rate, then no relaxation occurs between the stimuli, muscle
reaches max. tension and remains there & a sustained
contraction phase is obtained. 2.INCOMPLETE or UNFUSED TETANUS: if
repeated stimuli at a slower rate, then muscle fiber relaxes
slightly/incompletely between summated stimuli but the relaxation
remains incomplete. CAUSE: Enough Ca 2+ ions are maintained in the
muscle sarcoplasm so that contractile state is sustained without
allowing relaxation between AP.
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7. THE STAIRCASE/ TREPPE EFFECT DEFINITION: When a series of
maximal stimuli are delivered to the muscle at a frequency just
below tetanizing frequency (when muscle twitch due to previous
stimulus has just completed), the tension/amplitude developed
during each twitch increases till a max. height is reached & a
plateau is formed. This is called the Treppe/ staircase effect.
Because the tension rises in stages, like the steps in a staircase,
this phenomenon is called treppe, a German word meaning "stairs."
CAUSE: The rise is thought to result from a gradual increase in the
concentration of calcium ions in the sarcoplasm, in part because
the ion pumps in the sarcoplasmic reticulum are unable to recapture
them in the time between stimulations.
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Treppe Effect
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8. ISOTONIC VS. ISOMETRIC CONTRACTION
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ISOTONIC CONTRACTION There are two primary types of
contraction, depending on whether the muscle changes length during
contraction. They are: Isotonic contraction: occurs when muscle
contracts with shortening of length but against a constant load,
thus, the tension on the muscle remains constant (iso= same, tonic=
tension) OR A contraction that creates force & moves a load.
Isotonic contractions are used for body movements and for moving
external objects. E.g. picking up a book, a box.
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ISOMETRIC CONTRACTION Isometric contraction: occurs when muscle
contracts without shortening in length. (iso= same, metric= measure
or length) OR A contraction that creates force without movement.
Isometric contractions can be seen in 2 cases: 1.If the object you
are trying to lift is too heavy. 2.If the tension developed in the
muscle is deliberately less than needed to move the load. E.g.
standing for long time or holding up a glass of water while taking
sips.
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Physiologic basis of Isometric & Isotonic contractions: The
same internal events occur in both isotonic and isometric
contractions: Muscle excitation starts the sliding filament
cycling; the cross bridges start cycling; and filament sliding
shortens the sarcomeres, which exert force on the bone at the site
of the muscles insertion. During a given time, a muscle may shift
between isotonic & isometric contractions. E.g. when you lift a
book up it is isotonic contraction and when you keep holding the
book up while reading it is isometric contraction. NOTE: Since
Work=Distance X Load, Isotonic contractions do work where as
Isometric do not.
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9. ELECTROMYOGRAPHY Activity of motor units can be studied by
electromyography, the process of recording the electrical
activities of the muscle on a cathode ray oscilloscope. No
anesthesia is required. Small metal discs are placed on the skin
overlying the muscle as pick-up electrodes or hypodermic needle
electrodes are used. The record obtained with such electrodes is
the Electromyogram (EMG).
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10. RECRUITMENT If each motor unit contracts in an all-or-none
manner, how then can muscle create graded contractions of varying
force & duration? The answer lies in the fact that muscles are
composed of multiple motor units of different types. This allows
the muscle to vary contraction by: 1. Changing the types of motor
units that are active OR 2. Changing the number of motor units that
are responding at any one time. For a weak contraction of the whole
muscle, only one or a few of its motor units are activated. For
stronger & stronger contraction, more & more motor units
are recruited. This is called Motor Unit Recruitment.
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10. RECRUITMENT At rest EMG shows little or no activity With
minimum voluntary activity a few motor units discharge, & with
increasing voluntary effort more & more are brought into
play----- Recruitment of motor units Asynchronous Recruitment: One
way that CNS avoids fatigue in a sustained contraction The CNS
alternates between the different motor units supplying the same
muscle so that some of the motor units rest between contractions,
preventing fatigue. e.g. during a sustained contraction, only a
portion of the muscles motor units is involved as is necessary in
muscles supporting the weight of the body against the force of
gravity. The body alternates the motor units as shifts at a
factory, to give the motor units that have been active an
opportunity to rest while others take over. Changing of the shifts
is carefully co-ordinated so that the sustained contraction is
smooth rather than jerky.
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11. FAST vs SLOW FIBERS The skeletal muscle fibers are mainly
of 2 types: 1.SLOW or RED or TYPE I MUSCLE FIBERS 2.FAST or WHITE
or TYPE II MUSCLE FIBERS Every muscle of the body is composed of a
mixture of both fast & slow fibers. Simply: Fibers that react
rapidly are Fast fibers & muscles that react slowly with long
contractions are Slow fibers Color is determined by the protein
myoglobin
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11. FAST vs SLOW FIBERS SLOW-TWTCH/ RED/ Type I Small diameter
More myoglobin Fatigue resistant Mostly Oxidative Slow rate of
contraction Myosin ATPase activity LOW no. of myofilaments Red
Posture maintenance FAST-TWITCH/ WHTE/Type II Large diameter Less
myoglobin Easily fatigue Mostly glycolytic & oxidative Fast
rate of contraction Myosin ATPase activity HIGH no. of myofilaments
White Forceful & rapid movements
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12. MUSCLE HYPERTROPHY Definition: When the total mass of a
muscle increases, this is called Muscle Hypertrophy. The resulting
muscle enlargement comes from an increase in diameter of the muscle
fibers. It is in response to a regular & intensive use of that
particular muscle. e.g. body building. Physiologic Basis: in the
number of actin & myosin filaments causing increase in
thickness of individual muscle fibers---called fiber hypertrophy
Rate of synthesis of actin & myosin far greater Signaling
proteins triggered that turn on genes that direct the synthesis of
more of these contractile proteins.
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13. MUSCLE ATROPHY Definition: When the total mass of a muscle
decreases, it is called Muscle Atrophy. If a muscle is not used,
its actin and myosin content decreases, its filaments become
smaller and the muscle decreases in mass and becomes weaker.
Physiologic Basis: 1.When the muscle is prevented from doing work
even though the nerve supply is intact. e.g. in bed-ridden
patients, in a limb in a plaster of Paris cast. This type is thus
called Disuse Atrophy. 2.Atrophy also seen nerve supply to the
muscle is lost. This can be due to an accident or when motor
neurons supplying a muscle are destroyed.e.g. Poliomyelitis. Muscle
fiber becomes thin & low in proteins, glycogen and ATP. When
muscle continuously shortened then sarcomeres at the end of the
muscle fiber actually disappear
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14. MUSCLE HYPERPLASIA Under rare conditions of extreme muscle
force generation, the actual number of muscle fibers increase, in
addition to the fiber hypertrophy ----This increase in fiber number
is called Muscle Hyperplasia. Mechanism: Linear splitting of
previously enlarged fibers
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MUSCLE DISEASES
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MUSCLE CRAMPS Definition: Painful, sustained & involuntary
contractions of the muscle with motor units contracting repeatedly.
CAUSE: There can be many causes the most common of which are: Due
to increased excitability of the peripheral parts of the nerves
Electrolyte disturbance Nocturnal cramps (night cramps) Cramps due
to strenous exercise Dehydration.
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DUCHENNE MUSCULAR DYSTROPHY
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Duchenne Muscular Dystrophy Definition: It is a fatal muscle-
wasting disease that primarily strikes boys and leads to their
death before the age of 20. There is progressive degeneration of
contractile proteins of the muscle and their replacement with
fibrous tissue. It is a genetic X-linked disease.
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DUCHENNE MUSCULAR DYSTROPHY Mutation in the Dystrophin gene
located on X-chromosome Skeletal muscle lacks protein dystrophin (a
large protein that provides structural stability to the muscle
cells plasma membrane) Its absence leads to constant leakage of Ca
into the muscle cell Ca activates proteases that start damaging the
muscle Leads to increasing muscle weakness & fibrosis Symptoms
start at 2-3 years, patient wheel-bound at 10-12 years Usually die
at about 25-30 years of age (usually Males) Death is usually due to
respiratory failure or heart failure as the respiratory or heart
muscles become too weak. Milder disease is Beckers muscular
dystrophy