BIOL 2305
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
Muscle Tissue
Skeletal Muscle
Skeletal muscles attach to and cover the bony skeleton
Is controlled voluntarily (conscious control); responsible for overall
body motility
Contracts rapidly but tires easily
Is extremely adaptable
exert forces ranging from a fraction of an ounce to over 70
pounds
Has obvious stripes called striations caused by overlap of filaments
Each muscle cell is multinucleated
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Microscopic Anatomy - Skeletal Muscle Fiber
Microscopic Anatomy - Skeletal Muscle Fiber
Sarcoplasm contains glycosomes (granules of stored glycogen) and the oxygen-binding protein called
myoglobin
In addition to the typical organelles, fibers have
Sarcoplasmic reticulum – stores and releases Ca2+ ions
T tubules - modifications of the sarcolemma
Myofibrils – sarcomeres stacked end to end
Each muscle fiber is made of many myofibrils, 80% of the muscle volume, that contain the contractile
elements of skeletal muscle cells
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Myofibrils - Striations
Myofibrils are made up of sarcomeres stacked end to end
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) and Light I
(isotropic) bands, forming visual striations
The dark 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
The light I band has a darker midline called the Z disc (or Z line)
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Sarcomere
Sarcomere – the smallest contractile unit
of a muscle, formed from the repeating
pattern of alternating light and dark bands
The myofibril region between two
successive Z discs, has a central A band
and partial I bands at each end
Z disc - a line that separates one
sarcomere from another
M line - central line of the
sarcomere where myosin filaments
are anchored
H zone - the area where only
myosin filaments are present
I band - the area where only actin
filaments are present
A band - includes overlapping myosin and actin filaments
A myofibril is made of thousands of sarcomeres stacked end to 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
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Ultrastructure of Muscle
Arrangement of Filaments in a Sarcomere
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Sarcoplasmic Reticulum (SR)
SR – an elaborate, smooth ER that surrounds each myofibril; regulates intercellular Ca2+ concentration
Terminal Cisternae (Lateral Sacs) of SR – Perpendicular (transverse) channels at the A band - I band
junction
T tubules at each A band/I band junction – continuous with the sarcolemma.
T tubules conduct electrical impulses throughout the cell (every sarcomere) - signals for the
release of Ca2+ from adjacent terminal cisternae
Transverse tubules (T tubules)
Tubules formed by invaginations of the sarcolemma and flanked by the sarcoplasmic reticulum
They carry action potentials deep into the muscle fiber.
T tubules and SR provide tightly linked signals for muscle contraction.
Triad: Two terminal cisternae abut one T tubule
Triad allows T-tubules to physically link to Sarcoplasmic Reticulum
Voltage-sensitive Dihydropyridine (DHP) receptors on T-tubule surface open Ca2+ Release
Channels on SR
Interaction of T-tubule and Sarcoplasmic Reticulum
T-tubule membrane proteins called Dihydropyridine (DHP) receptors are voltage-sensitive L-type
calcium channels
But rather than allowing Ca2+ influx from ECF, DHP receptors physically open Ryanodine
receptors (Ryr) on SR
Action potential in T-tubule alters conformation of DHP receptor
Ryanodine receptors (aka SR foot proteins or Ca2+ Release Channels) release Ca2+ from the SR
terminal cisternae
Ca2+ flows down electrochemical gradient, diffuses toward Actin & Myosin filaments
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Interaction of T-tubule and Sarcoplasmic Reticulum
Sliding Filament Model of Contraction
Contraction refers to the activation of myosin 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 toward
the M-line in power strokes
Actin filaments slide past the myosin filaments so that the actin and myosin filaments overlap to a
greater degree
Actin filaments are moved toward M-line of sarcomere, Z lines become closer
Sliding Filament Model of Contraction
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Sliding Filament Model of Contraction
Skeletal Muscle Contraction
For contraction to occur, a skeletal muscle must:
Be stimulated by a nerve ending
Propagate an Action Potential along its sarcolemma
Have a rise in intracellualar Ca2+ levels
The series of events linking the action potential to
contraction is called Excitation-Contraction Coupling
Depolarization and Generation of an AP
The sarcolemma (muscle cell membrane), like other plasma
membranes, is polarized. There is a potential difference
(voltage) across the sarcolemma
ACh from the motor neuron binds to Nicotinic (Cholinergic)
receptors on motor end plate
Ligand-gated (ACh-gated) ion channels of Nicotinic
receptors open
Allowing Na+ and K+ to move across the membrane (more
Na+ than K+ due to greater Na+ electrochemical driving
force)
Net positive charge results in Depolarization called End
Plate Potential
End plate potential (EPP) - local depolarization in the
motor end plate
EPPs (normally) always reaches threshold, becoming
Action Potentials spreading across sarcolemma
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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
Excitation-Contraction Coupling
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Excitation-Contraction Coupling
 The AP 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.
 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)
Excitation-Contraction Coupling
Some of the Ca2+ binds to troponin
Troponin changes shape and causes tropomysin to move which exposes the myosin-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)
The ATP attached to the myosin head is split by ATPase causing the myosin heads to be
activated.
The activated myosin head attaches to the actin binding site, then swivels, producing a power
stroke which results in the sliding of the filaments. The ADP and P are released. Contraction
refers to the activation of myosin’s cross bridges – the sites that generate the force
Once the power stroke is complete, ATP again attaches to the myosin head causing the head to
detach from the actin site and return to its original position.
Cycle can then be repeated over and over again as long as calcium and ATP are present.
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Excitation-Contraction Coupling
Relaxation is caused by the breaking down of ACh by the enzyme acetylcholinesterase and the
reabsorption of calcium back into the SR
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
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Motor Unit
Motor unit - One motor neuron and the muscle fibers it innervates
Number of muscle fibers per motor unit varies widely
Number of motor units per muscle varies 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
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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
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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
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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:
Isometric
Muscle tension develops, but the load is not moved (muscle does not shorten)
Isotonic
Muscle tension overcomes (moves) the load and the muscle shortens (or lengthens)
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Isometric Contraction
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
the resistance > the force the muscle is producing
Isotonic Contraction
Muscle length changes (shortens or lengthens)
In isotonic contractions, the amount of change (distance in mm) is measured
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Energy Sources for Contraction
Cells are unable to use macronutrients directly for energy
Instead, the body must use them to make the high-energy
molecule ATP
ATP is the only energy source that is used directly for
contractile activity
As soon as it is hydrolyzed (4-6 seconds), ATP is regenerated by
three pathways:
Phosphocreatine (PCr) (aka creatine phosphate)
Transfer of high-energy phosphate group from
creatine phosphate to ADP
First energy storehouse tapped at onset of
contractile activity
Glycolysis
Glycolysis supports anaerobic or high-intensity
exercise; does not require O2
Oxidative phosphorylation
Oxidative phosphorylation (TCA cycle and
Electron Transport Chain) takes place within muscle
mitochondria if sufficient O2 is present
CP-ADP Reaction
Phosphocreatine (PCr) (aka creatine phosphate) is a phosphorylated creatine molecule that readily
donates a high-energy phosphate group to ADP, creating ATP as needed
Transfer of energy as a phosphate group is moved from PCr to ADP – the reaction is catalyzed by the
enzyme creatine kinase
PCr + ADP  creatine + ATP
Stored ATP and CP provide energy for maximum muscle power for 10-15 seconds
Side Note: Creatinine is a waste product of the break-down of phosphocreatine in muscle and is found
in low quantities in blood (0.6 to 1.2 mg/dL), high quantities in urine (40-300 mg/dL)
Anaerobic Glycolysis
Glucose is broken down into pyruvic acid to yield 2 ATP
When oxygen demand cannot be met, pyruvic acid is converted into lactic
Lactic acid diffuses into the bloodstream and can be used as energy source
the liver, kidneys, and heart
Lactic acid can also be converted back into pyruvic acid, glucose, or
glycogen by the liver
acid
by
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Glycolysis and Aerobic Respiration
Aerobic respiration occurs in mitochondria - requires O2
A series of reactions breaks down glucose for high yield of ATP
C6H12O6 + O2 
CO2
+ H2O + ATP
Glucose
+ Oxygen  Carbon Dioxide +
Water + Energy
Energy Sources for Contraction
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 glycogen stored in skeletal muscle
When no ATP is available, contractures (continuous contraction) may result (because cross bridges are
unable to detach without ATP)
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
are fatigue resistant (postural muscles of the neck and
back)
Fast oxidative fibers (Type II A) –
contract quickly
have fast myosin ATPases
have moderate resistance to fatigue (throughout body
for medium running and swimming)
Fast glycolytic fibers (Type II B) –
contract quickly
have fast myosin ATPases
are easily fatigued (muscles of the thighs for sprinting)
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Muscle Fiber Type: Speed of Contraction
Myoglobin (Mb)
Myoglobin (Mb)
A single-chain globular protein that contains a single heme group, which contains a single
Fe2+ ion, which binds to a single O2
In muscle fibers, myoglobin molecules act as local oxygen reserves for periods of intense
respiration
Located in skeletal and cardiac muscle, but not smooth.
Myoglobin is the “stationary cousin” of hemoglobin, the oxygen-carrying molecule in red blood cells
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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
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
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Smooth Muscle
Muscle fiber stimulated
Ca2+ released into the cytoplasm from ECF
Ca2+ binds with Calmodulin
Ca2+-Calmodulin Complex activates Mysoin Kinase
Myosin kinase phosphorylates myosin
Myosin can now bind with actin
Smooth Muscle Contraction
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The Role of Calcium in Smooth Vs Skeletal
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 Involuntary
Contracts at a fairly steady rate set by the heart’s pacemaker
Neural controls allow the heart to respond to changes in bodily needs
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