Skeletal Muscle Structure – Molecular Level
• Titin
– Connects myosin to the Z-lines in the sarcomere
– It is very elastic
• Able to stretch up to 3 times its resting length
– Important molecule because it is responsible for
muscle flexibility
Skeletal Muscle Contraction –
Force Generation
• Chemical or heat energy in the body is converted to
mechanical work or movement.
• A nerve impulse arrives at the neuromuscular
junction (NMJ) and stimulates the beginning of the
contraction process
– NMJ = synapse between a motor neuron and a skeletal
muscle cell
• Stimulation of the skeletal muscle cell triggers the
release of calcium ions from the terminal cisternae of
the sarcoplasmic reticulum
– Calcium catalyzes the contraction process
Skeletal Muscle Contraction –
Force Generation
• Calcium ions bind to troponin
– Troponin then pushes tropomyosin away thus exposing the active site
that it is covering on actin
• Myosin crossbridges have a strong affinity for the exposed
active site on the actin molecule
– Myosin binds to the exposed active site
• Myosin crossbridges pull on the actin myofilament pulling it
toward the center of the sarcomere
– This motion physically shortens the sarcomere, the myofibril, and
the muscle fiber.
“Sliding Filament” Mechanism
Contraction results from the sliding action of
interdigitating actin and myosin filaments
RELAXED:
CONTRACTED:
The Sliding-Filament Model
• A muscle contracts because the myosin and actin myofilaments
slide past each other
• Myosin cross bridges attach and pull, release, reattach and pull,
sliding the actin toward the center of the sarcomere
– Results in shortening of the I-band and the H-zone
• Neither actin nor myosin actually change length even though the
sarcomere is shortened in the contraction process
– The A-band remains the same length (length of myosin)
• A single attachment of the cross bridge results in about a 1%
shortening of the total muscle
– Muscles normally shorten 35 to 50% of their total resting length
The Sliding-Filament Model
• Each myosin cross bridge must attach and reattach many times
during a single contraction
– Called crossbridge cycling
• Power Stroke - Attachment of the myosin cross bridge to actin requires
energy
– Breakdown of ATP into ADP and P provides the energy required for
pulling on the actin myofilament
– ATP-ase catalyzes the breakdown of ATP
• Rigor – low-energy, strong bond between myosin and actin
• ADP and P are released from the myosin head thus breaking the bond
between the myosin crossbridge and actin
– Now the muscle is in a state of relaxation
• Cocking - Upon completion of the pulling mechanism, another ATP
attaches to the myosin crossbridge
– Preparation for another crossbridge cycle
Excitation-Contraction Coupling
• Sequence of events that links the nerve
impulse and skeletal muscle contraction
• Motor Neurons – stimulates skeletal muscles
– Excitatory effect
• When a skeletal muscle cell receives input
from a motor neuron, it depolarizes
– Depolarization causes the muscle cell to fire an
action potential
Excitation-Contraction Coupling
• Action Potentials
– Large changes in cell membrane potential (charge)
– Inside of the cell becomes more positive relative
to the outside of the cell
– Function to transmit information over long
distances
Excitation-Contraction Coupling
• Neuromuscular Junction (NMJ)
– The synapse between the motor neuron and the
muscle cell
• Synaptic Cleft
– The extra-cellular space between the motor
neuron and the muscle cell
Excitation-Contraction Coupling
• The NMJ releases a neurotransmitter from the
motor neuron into the synaptic cleft
• The neurotransmitter is acetylcholine (ACh)
• This neurotransmitter is synthesized by the
nerve cell and stored in synaptic vesicles
• When an nerve impulse reaches the NMJ,
the synaptic vesicles release acetylcholine
into the synaptic cleft.
Excitation-Contraction Coupling
4) Acetylcholine rapidly diffuses across the synaptic cleft to combine
with receptors on muscle cell membrane (sarcolemma)
– The muscle cell is also called the motor end plate membrane
5) ACh causes depolarization of the muscle cell membrane
– Generates an action potential
6) Acetylcholine bound to the receptor is rapidly decomposed by
acetylcholinesterase (enzyme) preventing continuous stimulation
of the muscle fiber.
Excitation-Contraction Coupling
• Stimulation of Contraction
– Action potential propogates along the sarcolemma
and down the T-tubules to reach the sarcoplasmic
reticulum
– Sarcoplasmic reticulum releases calcium
• Calcium is actively pumped into and stored in the SR
leaving a small concentration of calcium ions in the
sarcoplasm
– The action potential causes the calcium ions to be
released from the SR into the sarcoplasm
Excitation-Contraction Coupling
• When released from the SR, calcium travels toward
the myofilaments
– Calcium binds with troponin on the actin myofilament
causing a conformational change, which results in moving
tropomyosin off the active site
– Myosin heads are then able to bind to the G-actin on the
active sites
– This begins the contraction process of crossbridge cycling
Excitation-Contraction Coupling
• Crossbridge cycling continues as long as there is an adequate
supply of ATP and if there is stimulation from a motor neuron
• Crossbridge cycling stops if there is an inadequate supply of
ATP or if the motor neuron impulse stops
– When the motor neuron impulse stops, calcium ions are rapidly
pumped back into the sarcoplasmic reticulum for storage
– The calcium ion concentration in the sarcoplasm decreases
– Tropomyosin returns to its original position blocking the myosin
binding site on actin
– The muscle cell relaxes
Muscle Cell Metabolism
• How Muscle Cells Provide ATP to Drive the
Crossbridge Cycle…
– The sources of ATP:
• Available ATP in the sarcoplasm
• Creatine phosphate
• Glucose
Muscle Cell Metabolism
• Available ATP
– There is a limited supply of readily available ATP
– A small amount of ATP is stored in the myosin crossbridges
immediately available when the muscle begins to contract.
– Contraction uses up this source of ATP in about 6 seconds
making it necessary to have other sources of ATP available
Muscle Cell Metabolism
• Creatine Phosphate (CP)
– When the ATP stores in the myosin crossbridges are
exhausted, ADP and CP are used to regenerate ATP.
• CP + ADP = ATP + Creatine.
– The energy available from stored ATP and from the
reaction of joining ADP with CP provides only about 20
seconds worth of energy
• The muscles could contract only long enough to run a 100 m dash
on the energy from these sources
Muscle Cell Metabolism
• Glucose
• Cellular respiration of glucose is an energy source
utilized to generate ATP
• Muscle contractions that are longer than 15 - 20
seconds depend on cellular respiration of glucose as a
source of ATP
Muscle Cell Metabolism
• Recall
• Cells store glucose in the sarcoplasm in the form of glycogen
– The cell must break apart the glycogen molecules to release the
individual glucose molecules – this is called glycogenolysis
• The breakdown of glucose, called glycolysis, occurs in the sarcoplasm
of the muscle cell and does not require oxygen, it is anaerobic
• Glycolysis produces pyruvic acid, and a small amount of ATP.
• The majority of the ATP used by muscles is formed by aerobic
processes in the mitochondria.
– At low intensities, the muscle cell depends on aerobic glycolysis during
which oxidative phosphorylation becomes more important
Muscle Cell Metabolism – Changes with
Exercise Intensity
• Anerobic Metabolism
– Oxygen is not readily available
– During intense exercise, when the supply of oxygen cannot
keep up with metabolic demand of the cells, pyruvic acid
produced during glycolysis is converted to lactic acid.
• Lactic acid accumulates in the muscle resulting in the burning
sensation during short duration, high intensity muscular exercise
such as lifting weights
• Lactic acid is quickly removed from the muscle and taken to the
liver where it is converted to glucose
Muscle Cell Metabolism – Changes with
Exercise Intensity
• Aerobic Metabolism
– Oxygen is readily available
– During prolonged, low-intensity exercise, the muscles are
supplied with adequate oxygen by the protein myoglobin
– Myoglobin
• Similar to hemoglobin (oxygen binding protein in the blood)
• Myoglobin has a high affinity for oxygen and binds to it loosely
inside muscle cells
– Myoglobin brings oxygen into the muscle cell and stores it
temporarily
– This provides a continuous supply of oxygen even when blood flow to
the muscle is reduced
Muscle Cell Metabolism – Changes with
Exercise Intensity
• When exercise stops, the body's need for oxygen
continues for a period of time
• The body responds to this need by continuing to
breathing heavily until all the sources of ATP have been
replenished
• Oxygen Debt
– The amount of oxygen necessary to restore the resting
metabolic state of the body
• A better, and more currently accepted, term to describe
the events following exercise is recovery oxygen
consumption
Muscle Cell Metabolism – Changes with
Exercise Intensity
• Recovery oxygen consumption
– Includes the oxygen needed to:
• Restore muscles to their resting metabolic condition
• Convert lactic acid to pyruvic acid in the liver
• Replenish cellular stores of glycogen, creatine phosphate,
and ATP
• Return resting body temperature to normal
• Return the heart muscle and the muscles of respiration to
normal, which need repair from the minor tissue damage
that occurs due to exercise
• The amount of oxygen needed to meet recovery oxygen
consumption demands depends on an individual's physical
condition and the duration and intensity of the exercise session.
Types of Skeletal Muscle Fibers
• Not all muscle fibers are the same physiologically
• Muscles vary depending on:
– The predominant pathway utilized to synthesize ATP
• Oxidative fibers - predominantly aerobic pathways
– Oxidative phosphorylation in the mitochondria
– Fatigue-resistant fibers
• Glycolytic fibers – predominantly anaerobic pathways
– Glycolysis in the sarcoplasm
– Fatigable fibers
– The amount of myoglobin
• Red fibers - high amounts of myoglobin
• White fibers - small amounts of myoglobin
– Efficiency of ATPase
• Fast twitch fibers - decompose ATP rapidly
• Slow twitch fibers - decompose ATP slowly
Types of Skeletal Muscle Fibers
• Slow-twitch fatigue-resistant fibers
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–
–
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Slow oxidative fibers, or red muscle fibers.
Contain abundant myoglobin giving them their red color.
Slow acting ATPase enzymes
Abundant mitochondria
• Depend upon aerobic pathways for production of ATP
– Endurance type muscles
• Able to deliver strong, prolonged contractions.
• Examples:
– Postural muscles - spinal extensors
– Anti-gravity muscles - calf muscle
Types of Skeletal Muscle Fibers
• Fast-twitch fatigable fibers
– Fast glycolytic fibers, or white muscle fibers.
– Contain small amounts of myoglobin
– Fast acting ATPase enzymes
• Allows the muscle fiber to contract rapidly
– Few mitochondria
• Contract for limited periods of time because fatigue rapidly
– Plenty of glycogen
• Depends on anaerobic metabolism
– Extensive sarcoplasmic reticulum
• Rapidly releases and stores calcium ions contributing to rapid contractions
– Best suited for short duration, high intensity contractions
Types of Skeletal Muscle Fibers
• Intermediate Fibers
– Fast-twitch fatigue-resistant fibers
• Fast glycolytic fibers
• Pale muscle fibers
– Characteristics lie between the red and white
fibers
Types of Skeletal Muscle Fibers
• Most of the body's muscles contain a mixture of fiber
types.
• It is the motor nerve that innervates the muscle cell that
determines its type
– Therefore, all of the muscle cells in a single motor unit are of
the same type
– Motor Unit – a motor neuron and all of the muscle fibers it
innervates
• Examples:
– Running – the motor nerve stimulates the motor units
containing fast-twitch fibers.
– Posture – the motor nerve stimulates the motor units
containing slow-twitch fibers.
Types of Skeletal Muscle Fibers
• Slow twitch fibers are recruited first
– This is because they are found in small motor
units
• Fast twitch fibers are recruited last
– This is because they are found in large motor units
Types of Skeletal Muscle Fibers
• People are genetically predisposed to have
relatively more of one fiber type than another
– People who excel at marathon running have
higher percentages of slow twitch fatigue resistant
muscle fibers
– People who excel at sprinting have higher
percentages of fast twitch fatigable fibers