MCB 244

Anatomy and Physiology

Fall 2024
Instructor: Dr. Bharathi Aravamudan

Muscular System- Part I

 Learning Outcomes: Muscular System Part I
At the end of this lecture, students must be able to:
 Explain the general functions and characteristics of skeletal muscle
 Describe the microscopic anatomy of a skeletal muscle fiber
 Explain the organization of myofibrils, myofilaments, and sarcomeres
 Define and describe a motor unit
 Identify and describe the components of a neuromuscular junction
 Describe the steps in excitation-contraction coupling
 Summarize the changes that occur within a sarcomere during contraction and relaxation
 Describe how ATP is made available within skeletal muscle through myosin
kinase, creatine kinase, glycolysis, and aerobic cellular respiration
 Compare and contrast the three skeletal muscle fiber types
 Explain the events that occur in motor unit recruitment as the intensity of stimulation is
increased
 Define muscle fatigue, and explain some of its causes
 Describe the features of cardiac muscle and smooth muscle
 Explain the sequence of steps in smooth muscle contraction and how to control it
 Explain the primary functional difference between multiunit and single-unit smooth muscle

2
 Functions of Skeletal Muscle

 Move the body: move bones, make facial expressions, speak,

breathe, swallow
 Maintain posture: stabilize joints, maintain body position
 Protect and support: package internal organs and hold them in
place
 Regulate elimination of materials: circular sphincters control
passage of material at orifices
 Produce heat: help maintain body temperature

3
 Characteristics of Skeletal Muscle Tissue
 Excitability: ability to respond to a stimulus by changing electrical
membrane potential
 Conductivity: involves sending an electrical change down the length
of the cell membrane
 Contractility: exhibited when filaments slide past each other;
enables muscle to cause movement
 Extensibility: ability to be stretched
 Elasticity: ability to return to original length following a lengthening
or shortening

4
 Test your understanding…

1. What are the five major functions of skeletal muscle?

2. Compare and contrast the skeletal muscle characteristics of
contractility, extensibility, and elasticity.

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 Structural Organization of
Skeletal Muscle

Gross Anatomy of Skeletal Muscle

 Each skeletal muscle is an
organ: Multiple types of
tissues working together:
skeletal muscle fibers,
connective tissue, blood
vessels, and nerves
 Muscle fibers bundled within
a fascicle: a whole muscle
contains many fascicles: a
fascicle consists of many
muscle fibers (a muscle fiber
is a muscle cell)

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 Connective tissue components:
 Three concentric layers of wrapping
o Epimysium: dense irregular connective tissue wrapping whole muscle
o Perimysium: dense irregular connective tissue wrapping fascicle; houses many
blood vessels and nerves
o Endomysium: areolar connective tissue wrapping individual fiber; delicate
layer for electrical insulation, capillary support, binding of neighboring cells
 Attachments of muscle to bone (or to skin or to another muscle)
can be tendons or aponeuroses
o Tendon: cordlike structure of dense regular connective tissue
o Aponeurosis: thin, flattened sheet of dense irregular tissue
 Deep fascia: dense irregular CT superficial to epimysium; separates
individual muscles; binds muscles with similar functions
 Superficial fascia: areolar and adipose CT superficial to deep fascia;
separates muscles from skin

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Blood vessels and nerves
 Skeletal muscle is vascularized, has extensive blood vessels that

deliver oxygen and nutrients, and remove waste products

 Skeletal muscle is innervated by somatic motor neurons
o Axons of neurons branch, terminate at neuromuscular junctions
 Skeletal muscle is considered a voluntary muscle because
contraction is voluntarily controlled

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Microscopic Anatomy of Skeletal Muscle

Structure and Organization of a

Skeletal Muscle Fiber

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Parts of a muscle cell (myofiber):
 Sarcoplasm (muscle cytoplasm) has typical organelles plus contractile proteins
and other specializations
 Multiple nuclei (individual cells are multinucleated/ syncytial)
Cell is formed in embryo when multiple myoblasts fuse
 Some nearby myoblasts become undifferentiated satellite cells for support and repair
of muscle fibers
 Sarcolemma (plasma membrane) has voltage-gated ion channels that allow for
conduction of electrical signals
 Also has T-tubules (transverse tubules) that extend deep into the cell, and contain
voltage-sensitive (gated) calcium channels
 Myofibrils (hundreds to thousands per cell): bundles of myofilaments enclosed in
sarcoplasmic reticulum
 Sarcoplasmic reticulum (SR): internal membrane complex similar to smooth ER
 Terminal cisternae: blind sacs of sarcoplasmic reticulum; serve as reservoirs for calcium
ions; two cisternae with T-tubule in between = triad
 SR contains calcium pumps that import calcium, which binds to calmodulin and
calsequestrin
 Contains calcium release channels that are triggered by electrical signal traveling down
T-tubule to release calcium into sarcoplasm
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Sarcolemma and T-tubules

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Myofilaments are contractile proteins within myofibrils; two types:
 Thick filaments consist of bundles of many myosin protein molecules; myosin
heads point toward ends of the filament
 Thin filaments: twisted strands of actin (each F-actin composed of G-actin
monomers)
o G-actin has myosin binding site where myosin heads attach
o Tropomyosin and troponin are present; regulatory proteins

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Organization of a sarcomere
 Myofilaments arranged in repeating units called sarcomeres
 Composed of overlapping thick and thin filaments
 Delineated at both ends by Z discs, which have specialized proteins perpendicular
to myofilaments and anchors for thin filaments
 Positions of thin and thick filaments give rise to alternating I-bands and A-bands

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 I bands: light-appearing regions that contain only thin filaments; bisected by Z
disc; get smaller when muscle contracts (can disappear with maximal
contraction)
 A band: dark-appearing region that contains thick filaments and overlapping thin

filaments; contains H zone and M line; makes up central region of sarcomere

o H zone: central portion of A band where only thick filaments are present; no

thin filament overlap; disappears with maximal muscle contraction

o M line: middle of H zone; a protein meshwork structure that acts as an

attachment site for thick filaments

 Other structural and functional proteins
o Connectin: extends from Z disc to M line; stabilizes thick filaments and has

“springlike” properties (passive tension)

o Dystrophin: anchors some myofibrils to sarcolemma proteins; abnormalities of

this protein cause muscular dystrophy

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 Structure of a Sarcomere:
Longitudinal Section

Cross Section

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 Clinical View: Muscular Dystrophy
 Collective term for hereditary diseases where skeletal muscles

degenerate
 Duchenne muscular dystrophy (DMD) is most common type
 Defective or insufficient dystrophin
 Sarcolemma damaged during muscle contraction
o Calcium enters cells, damages proteins
 Problems begin in early childhood
o Walking difficulties, muscle atrophy, postural issues
 Incurable; patients rarely live beyond age 30

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Mitochondria and other structures associated with energy production
 Muscle fibers have abundant mitochondria for aerobic ATP
production
 Myoglobin within cells allows storage of oxygen used for aerobic
ATP production
 Glycogen is stored for when fuel is needed quickly
 Creatinine phosphate can quickly give up its phosphate group to
help replenish ATP supply

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 Innervation of Skeletal Muscle Fibers
Motor unit: a motor neuron and all the muscle fibers it controls
 Axons of motor neurons from spinal cord (or brain) innervate many muscle fibers
 Number of fibers a neuron innervates varies
o Small motor units have < 5 muscle fibers; allow for precise control of force output
o Large motor units have thousands of muscle fibers; allow for production of large
amount of force (but not precise control)
 Fibers of a motor unit are dispersed throughout the muscle (not just in one
clustered compartment)

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Neuromuscular Junction

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Neuromuscular Junction
 Location where motor neuron innervates muscle
 Usually mid-region of muscle fiber
 Has the following parts: synaptic knob, synaptic cleft, motor end plate
Synaptic knob

o Expanded tip of the motor neuron axon
o Houses synaptic vesicles -Small sacs filled with neurotransmitter Acetylcholine (ACh)
o Has Ca2+ pumps in plasma membrane, which establish Ca 2+ gradient, with more
outside the neuron
o Has voltage-gated Ca2+ channels in membrane; Ca2+ flows into cell (down
concentration gradient) if channels open
 Motor end plate
o Specialized region of sarcolemma with numerous folds
o Has many ACh receptors- plasma membrane protein channels that are opened by
the binding of Ach to allow Na+ entry and K+ exit
 Synaptic cleft is a narrow fluid-filled space; separates synaptic knob from motor end plate;
the enzyme acetylcholinesterase (breaks down ACh molecules) resides here

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 Skeletal Muscle Fibers at Rest
Muscle fibers exhibit resting membrane potential (RMP)
 Fluid inside cell is negative compared to fluid outside cell
 RMP of muscle cell is about −90 mV
 RMP established by leak channels and Na+/K+ pumps
(voltage-gated channels are closed)

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 Test your understanding…

1. Sketch a diagram of a cross section of a muscle, and label the

fascicle, muscle fiber, myofibrils, and their associated
connective tissue coverings.
2. Draw and label a diagram of a sarcomere.
3. Place the following gross anatomic and microscopic anatomic
structures in order from largest to smallest: fascicle, myofibril,
myofilament, muscle, muscle fiber, and sarcomere. Describe
their anatomic relationship
4. Describe a motor unit, and explain why motor units vary in size.
5. Diagram and label the anatomic structures of a neuromuscular
junction.
6. Describe the distribution or Na+ and K+ at the sarcolemma.
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Overview of Events in Skeletal Muscle Contraction

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 Excitation of a Skeletal Muscle Fiber
1

1a. Calcium entry at synaptic knob

 Nerve signal travels down axon, opens voltage-gated Ca2+ channels
 Ca2+ diffuses into synaptic knob
 Ca2+binds to proteins on surface of synaptic vesicles

1b. Release of ACh from synaptic knob

 Vesicles merge with cell membrane at synaptic knob: exocytosis
 Thousands of ACh molecules released from about 300 vesicles

1c. Binding of ACh at motor end plate

 ACh diffuses across cleft, binds to receptors, excites fiber

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1

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 Clinical View: Myasthenia Gravis
 Autoimmune disease, primarily in women
 Antibodies bind to ACh receptors in neuromuscular junctions
 Receptors removed from muscle fiber by endocytosis
 Results in decreased muscle stimulation
 Rapid fatigue and muscle weakness
 Eye and facial muscles often involved first
 May be followed by swallowing problems, limb weakness

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 Excitation-Contraction Coupling
2

 Stimulation of the fiber is coupled with the sliding of filaments

 Coupling includes the end-plate potential (EPP), muscle action potential, and
release of Ca2+ from the sarcoplasmic reticulum

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Sarcolemma, T-tubules, and Sarcoplasmic Reticulum
2
2a. End-plate potential (EPP)
 ACh receptors: chemically gated channels that open when ACh binds to them
 Na+ diffuses into the cell through the channels
(while a little K+ diffuses out)
 Cell membrane briefly becomes less negative at the end plate region
 EPP is local but it does lead to the opening of voltage-gated ion channels in
the adjacent region of the sarcolemma

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2b. Initiation & propagation of action potential along the sarcolemma and T-tubules
i. Action potential (AP): a rapid rise (depolarization) and fall (repolarization) in
the charge of the membrane
 EPP reaches threshold by causing nearby voltage-gated Na+ channels to open
ii. Na+ diffuses into the cell through voltage-gated channels
 Cell depolarizes: becomes less negative, eventually becomes +30 mV
 This results in the opening of adjacent voltage-gated Na+ channels and more
Na+ entry
 A chain reaction occurs as depolarization is propagated down the membrane
and T-tubules
iii. Just after Na+ channels open, they close and voltage-gated K+ channels open
 K+ diffuses out of the cell
 Cell repolarizes: returns to -90mV
 Repolarization is then propagated down the membrane and
T-tubules
iv. While the cell is depolarizing and repolarizing it is in refractory period- unable
to respond to another stimulation
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Events of an Action Potential at the Sarcolemma 2b

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AP travels down T-tubules; causes voltage-sensitive Ca2+ channels in T-tubule
membrane to trigger the opening of Ca2+ release channels in SR terminal cisternae
2c. Release of Ca2+ from the sarcoplasmic reticulum: Ca2+ interacts with myofilaments
triggering contraction

2c

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 3
Sarcomere:
Crossbridge Cycling

The third physiologic event

in muscle contraction is the
binding of calcium and
crossbridge cycling
Calcium binding
 When Ca2+ binds to
troponin, it triggers
crossbridge cycling;
Troponin and
tropomyosin move so
actin is exposed

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 3

Crossbridge cycling: four repeating steps

1) Crossbridge formation: Myosin head attaches to exposed binding site on actin
2) Power stroke: Myosin head pulls thin filament toward center of sarcomere; ADP
and Pi released
3) Release of myosin head: ATP binds to myosin head causing its release from actin
4) Reset myosin head: ATP split into ADP and Pi by myosin ATPase: this provides
energy to ‘cock’ the myosin head
 Cycling continues as long as Ca2+ and ATP are present
 Results in sarcomere shortening as Z discs move closer together
 Narrowing (or disappearance) of H zone and I band
 Thick and thin filaments remain the same length but slide past each other

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Sarcomere Shortening

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 Clinical View: Muscular Paralysis and Neurotoxins
Tetanus
 Spastic paralysis caused by toxin from Clostridium tetani
 Blocks release of inhibitory neurotransmitter in spinal cord,
resulting in overstimulation of muscles
 Vaccination prevents this life-threatening condition
Botulism
 Muscular paralysis caused by toxin from Clostridium
botulinum
 Prevents release of ACh at synaptic knobs
 Although toxin ingestion can be life-threatening, careful
injections of it can treat spasticity (for example, due to
cerebral palsy) or can be used for cosmetic purposes
(diminishing wrinkles)
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 Skeletal Muscle Relaxation

Events in muscle relaxation

 Termination of nerve signal and ACh release from motor neuron
 Hydrolysis of ACh by acetylcholinesterase
 Closure of ACh receptor causes cessation of end plate potential
 No further action potential generation
 Closure of calcium channels in sarcoplasmic reticulum
 Return of Ca2+ to sarcoplasmic reticulum by pumps
 Return of troponin to original shape
 Return of tropomyosin blockade of actin’s myosin binding sites
 Return of muscle to original position due to its elasticity

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 Test your understanding…
1. What triggers the binding of synaptic vesicles to the synaptic
knob membrane to cause exocytosis of ACh?
2. What two events are linked in the physiologic process called
excitation-contraction coupling?
3. Describe the events of excitation-contraction coupling.
4. What is the function of Ca2+ in skeletal muscle contraction?
5. Describe the four processes that repeat in crossbridge cycling
to cause sarcomere shortening.
6. What causes the release of the myosin head from actin? What
resets the myosin head?
7. How do acetylcholinesterase and Ca2+ pumps function in the
relaxation of a muscle?
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 Supplying Energy for Skeletal Muscle Metabolism
 Muscle cells have only a little ATP in storage: stored ATP is spent after about 5
seconds of intense exertion; additional ATP rapidly produced via myokinase
(phosphate transferred from one ADP to another to make ATP)
 Three ways to generate additional ATP in skeletal muscle fiber: Creatine
phosphate, Glycolysis and Aerobic cellular respiration

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Creatine phosphate
 Contains a high-energy bond between creatine and phosphate
 Phosphate can be transferred to ADP to form ATP
 Catalyzed by creatine kinase
 10-15 seconds of additional energy
Glycolysis
 Does not require oxygen
 Glucose (from muscle’s glycogen or through blood) is converted to two
pyruvate molecules
 2 ATP released per glucose molecule
 Occurs in cytosol
Aerobic cellular respiration
 Requires oxygen
 Occurs within mitochondria
 Pyruvate oxidized to carbon dioxide: Transfer of chemical bond energy to

NADH and FADH2; energy used to generate ATP by oxidative phosphorylation;

produces a net of 30 ATP
 Triglycerides can also be used as fuel to produce ATP: more ATP from
triglycerides with longer fatty acid chains 39
Lactate formation and its fate
 Lactate formation from pyruvate occurs under conditions of low

oxygen availability
 Pyruvate is converted to lactate by lactate dehydrogenase
 Lactate can be used as fuel by skeletal muscle fiber or enter blood

and taken up by cardiac muscle or liver

 Lactic acid cycle: cycling of lactate to liver where it’s converted to

glucose, and transport of glucose back to muscle

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Energy supply and varying intensity of exercise
 For a 50-meter sprint (<10 seconds): ATP supplied primarily by phosphate
transfer system
 For a 400-meter sprint (< 1 minute): ATP supplied primarily by glycolysis after first
few seconds
 For a 1500-meter run (> 1 minute): ATP supplied primarily by aerobic processes
after first minute

Utilization of
Energy Sources

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Oxygen debt
 Amount of additional oxygen needed after exercise to restore pre-
exercise conditions
 Additional oxygen required to
o Replace oxygen on hemoglobin and myoglobin
o Replenish glycogen
o Replenish ATP and creatine phosphate
o Convert lactic acid back to glucose

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 Test your understanding…

1. Additional ATP is made immediately available in skeletal

muscle through which phosphate-containing molecules?

2. What are the various means for making ATP available in a

1500-meter race?

3. What is oxygen debt, and how is the additional oxygen used

following intense exercise?

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 Criteria for Classification of Skeletal Muscle Fiber Types
Skeletal muscle fibers are classified based on:
1. Type of contraction generated
2. Means for supplying ATP
Type of contraction generated
 Differences in power, speed, and duration
o Power related to diameter of muscle fiber
o Speed and duration related to type of myosin ATPase, quickness of action
potential propagation, and quickness of Ca2+ release and reuptake by
sarcoplasmic reticulum
 Fast-twitch fibers are more powerful and have quicker and briefer contractions
than slow twitch fibers
Means for supplying ATP: Oxidative versus glycolytic fibers
 Oxidative fibers (fatigue-resistant) use aerobic cellular respiration
o Extensive capillaries, many mitochondria, large supply of myoglobin; aka Red
fibers
 Glycolytic fibers (fatigable) use anaerobic cellular respiration
o Fewer capillaries, fewer mitochondria, small supply of myoglobin, large
glycogen reserves, aka White fibers 44
3 types of skeletal muscle fibers:
1. Slow oxidative (SO) fibers (type I)
o Contractions are slower and less powerful
o High endurance since ATP supplied
aerobically
o About half the diameter of other fibers,
red in color due to myoglobin
2. Fast oxidative (FO) fibers (type IIa,
intermediate)
o Contractions are fast and powerful
o Primarily aerobic respiration, but delivery
of oxygen lower
o Intermediate size, light red in color

3. Fast glycolytic (FG) fibers (type IIx, fast

anaerobic)
o Contractions are fast and powerful
o Contractions are brief, as ATP production is
primarily anaerobic
o Largest size, white in color due to lack of
myoglobin
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 Test your understanding…

1. Explain how a fast-twitch fiber differs from a slow-twitch

fiber and how an oxidative fiber differs from a glycolytic
fiber.

2. Which skeletal muscle fiber type is slow and fatigue-

resistant? What is the advantage of this skeletal muscle
fiber type?

3. Muscles that maintain posture are composed primarily of

what type of skeletal muscle fibers?

46
Muscle tension in skeletal muscle
 Force generated when a muscle is stimulated to contract
 Lab experiments measure tension and graph it (myogram)

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Muscle Twitch
 A twitch is a brief contraction to a single stimulus
 The minimum voltage that triggers a twitch is the threshold
 Periods of the twitch:
o Latent period: Time after stimulus but before contraction begins; no change in
tension
o Contraction period: time when tension is increasing; begins as power strokes
pull thin filaments
o Relaxation period: time when tension is decreasing to baseline; begins with
release of cross-bridges; generally lasts a little longer than contraction period

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Changes in Stimulus Intensity: Motor
Unit Recruitment
 Muscle is stimulated repeatedly
 As voltage increases, more units are
recruited to contract
 Recruitment (aka multiple motor unit
summation) explains how muscles
exhibit varying degrees of force: recruit
few motor units to lift pencil vs many to
lift suitcase
 Above a certain voltage, all units are
recruited, and so maximum contraction
occurs (regardless of how much higher
voltage is)
 Recruitment order based on size of
motor units: small first, large last

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Wave summation (temporal summation)
 If stimulus frequency set at about 20 per second, relaxation is not completed
between twitches; contractile forces add up to produce higher tensions
 If frequency is increased further, myogram exhibits incomplete tetany- tension
increases and twitches partially fuse
 If frequency is increased further still (for example, 40 to 50 per second), myogram
exhibits tetany- tension trace is a smooth line without relaxation
 High frequency stimuli lead to fatigue (decreased tension production)

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 Test your understanding…

1. What events are occurring in a muscle that produce the

different components of a muscle twitch (latent period,
contraction, and relaxation)?

2. What is recruitment? Explain its importance in the body.

3. What happens to skeletal muscle during wave summation?

Explain its importance in the body.

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Muscle tone
 Resting tension in a muscle
 Generated by involuntary nervous stimulation of muscle
 Some motor units stimulated randomly at any time
 Change continuously so units not fatigued
 Do not generate enough tension for movement
 Decreases during deep sleep
Isometric contraction
 Although tension is increased, it is insufficient to overcome resistance
 Muscle length stays the same, as when holding a weight while arm doesn’t
move
Isotonic contraction
 Muscle tension overcomes resistance resulting in movement
 Tone stays constant, but length changes
 Concentric contraction: muscle shortens as it contracts, as in the biceps brachii
when lifting a load
 Eccentric contraction: muscle lengthens as it contracts, as in the biceps brachii
when lowering a load

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 Isometric Versus Isotonic Contraction
Isometric contraction
 Although tension is increased, it is insufficient to overcome resistance
 Muscle length stays the same, as when holding a weight while arm doesn’t
move
Isotonic contraction
 Muscle tension overcomes resistance resulting in movement
 Tone stays constant, but length changes

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 Concentric contraction: muscle shortens as it contracts, as in the biceps brachii
when lifting a load
 Eccentric contraction: muscle lengthens as it contracts, as in the biceps brachii
when lowering a load

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 Clinical View: Isometric Contraction and Increase in Blood Pressure
Sustained isometric contractions
 Associated with increase in blood pressure
 May be a concern for those with baseline high blood pressure
 For example, shoveling snow
 General peripheral constriction (from cold) elevates pressure
 Isometric contractions of shoveling also increase pressure

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Length-Tension Relationship
The tension a muscle produces depends on its length at the time of stimulation
 Fiber at resting length generates maximum contractile force: optimal overlap of
thick and thin filaments
 Fiber at a shortened length generates weaker force: filament movement is
limited (already close to Z disc)
 Fiber at an extended length generates weaker force: minimal thick and thin
filament overlap for crossbridge formation
Length-Tension Curve

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Muscle fatigue: reduced ability to produce muscle tension- primarily
caused by a decrease in glycogen stores during prolonged exercise

Other possible causes of fatigue:

 Excitation at neuromuscular junction
o Insufficient Ca2+ to enter synaptic knob
o Decreased number of synaptic vesicles
 Excitation-contraction coupling
o Altered ion concentrations impair action potential conduction and Ca2+ release
from sarcoplasmic reticulum
 Crossbridge cycling
o Excessive Pi slows release of Pi from myosin head
o Less Ca2+ available for troponin (some Ca2+ is bound to Pi)

57
 Test your understanding…
1. Explain the function of skeletal muscle tone.
2. When you flex your biceps brachii while doing “biceps curls,”
what is the type of muscle contraction – is it an isometric
contraction or an isotonic contraction?
3. Describe the relative force of contraction that can be
developed in your back muscles when you bend at the knees
to lift an object and when you bend at the waist to lift an
object, based on the length-tension relationship. Explain the
significance.
4. How can muscle fatigue result from changes in each of the
three primary events of skeletal muscle contraction?

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Effects of Exercise
Changes in muscle from a sustained exercise program
 Endurance exercise leads to better ATP production (more mitochondria)
 Resistance exercise leads to hypertrophy: muscle increases in size due to
increases in synthesis of contractile proteins, glycogen reserves and
mitochondria; limited amount of hyperplasia (increase in number of fibers)
Changes in muscle from lack of exercise
 Atrophy: decrease in size due to lack of use (e.g., someone wearing a cast);
initially reversible, but becomes permanent if extreme
Effects of Aging
Loss of muscle mass with age
 Slow loss begins in person’s mid-30s due to decrease in activity
 Decreased size, power, and endurance of skeletal muscle
 Loss in fiber number and diameter (decrease in myofibrils)
 Decreased O2 storage capacity and circulatory supply to muscles with exercise

Reduced capacity to recover from injury

 Decreased number of satellite cells
 Fibrosis: muscle mass often replaced by dense regular connective tissue;
decreased flexibility
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 Clinical View: Anabolic Steroids as Performance-Enhancing
Compounds
Anabolic steroids
 Synthetic substances that mimic testosterone
 Require prescription for legal use
 Stimulate manufacture of muscle proteins
 Popular performance enhancers
 Side effects include
o Increased risk of heart disease and stroke
o Kidney damage and liver tumors
o Testicular atrophy, breast development in males
o Acne, high blood pressure, aggressive behavior
o Growth of facial hair and menstrual irregularities in women

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 Test your understanding…

1. What anatomic changes occur in a skeletal muscle fiber

when it undergoes hypertrophy?

2. What changes in skeletal muscle occur as a result of aging?

61
 Cardiac Muscle Tissue

Cardiac muscle cells:

 Short, branching fibers
 One or two nuclei
 Striated (contain sarcomeres)
 Many mitochondria (use aerobic
respiration)
 Intercalated discs join ends of
neighboring fibers; contain
desmosomes and gap junctions
 Contractions started by heart’s
autorhythmic pacemaker cells
 Heart rate and contraction force
influenced by autonomic
nervous system

62
 Test your understanding…

What are three anatomic or physiologic differences between

skeletal muscle and cardiac muscle?

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 Smooth Muscle
 Smooth muscle is found in a
variety of organ systems with a
variety of roles
 Examples:
 In blood vessels of cardiovascular
system- helps regulate blood
pressure and flow
 In bronchioles of respiratory
system- controls airflow to alveoli
 In intestines of digestive system-
mixes and propels materials
 In ureters of urinary system-
propels urine from kidneys to
bladder
 In uterus of female reproductive
system
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Microscopic Anatomy of Smooth Muscle

65
 Smooth muscle cells have fusiform shape (wide in the middle with tapered ends)
 Smaller than skeletal muscle fibers
 Sarcolemma has varied types of Ca2+ channels (gated by chemicals or voltage)
 Transverse tubules absent, but surface area is increased by flask-like
invaginations called caveolae
 SR is sparse; so extracellular environment is important source of Ca2+
Arrangement of anchoring proteins and contractile proteins of smooth muscle
 Cytoskeleton composed of extensive intermediate filaments
o Dense bodies: points where intermediate filaments interact within sarcoplasm
o Dense plaques: points where intermediate filaments attach on inner
sarcolemma
 Contractile proteins
o Arranged between dense bodies and dense plaques
o Oriented at oblique angles to longitudinal axis of cell
o Contraction causes a twisting motion
 Lack sarcomeres and Z discs (smooth = no striations)

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 Like skeletal muscle, smooth muscle filaments have actin, myosin, and
troponin
 Unlike skeletal muscle, smooth muscle
o Filaments have myosin heads along their entire length; can form
additional cross bridges
o Filaments can perform the latchbridge mechanism: myosin attaches to
actin for extended time without using extra ATP
o Has calmodulin: protein that binds Ca2+ to trigger contraction
o Has myosin light-chain kinase (MLCK): enzyme that phosphorylates
myosin heads when activated by calmodulin
o Has myosin light-chain phosphatase: enzyme that dephosphorylates
myosin head (required for relaxation)

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Smooth Muscle Contraction

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Relaxation of smooth muscle
 Cessation of stimulation
 Removal of Ca2+ from sarcoplasm
 Dephosphorylation of myosin by myosin light-chain phosphatase
 Can be slow to relax due to latch-bridge mechanism

Smooth muscle contraction characteristics

 Long latent period
o Takes time to phosphorylate myosin head
o Slow ATPase activity
 Long duration
o Slow calcium pumps
o Need for dephosphorylation of myosin head
o Latchbridge mechanism
 Slowness fits its functional requirements
 Extended contractions maintain continuous tone (as in blood vessel walls)

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 Smooth muscle contraction is fatigue-resistant
o Energy requirements low compared to skeletal muscle
o Can maintain contraction without ATP through latchbridge mechanism
 Broad length-tension curve
o Lacks limitations because no Z discs
o Myosin heads present in center of thick filaments
o Can contract forcefully, even when 50% to 200% of resting length; for
example, allows emptying bladder regardless of amount of urine

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Control of smooth muscle
 Autonomic (involuntary) nervous system secretes transmitters
o Muscle’s response depends on neurotransmitter present and muscle’s
receptor for it
o For example, smooth muscle of bronchioles contracts in response to ACh and
relaxes in response to norepinephrine
 Response to stretch
o Myogenic response is contraction in reaction to stretch
o Stress-relaxation response is relaxation after prolonged stretch
 Other stimulating factors include:
o Various hormones, low pH, low O2, high CO2, certain drugs, pacemaker cells

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 Functional Categories of Smooth Muscle
Two categories of smooth muscle: multiunit and single unit
Multiunit smooth muscle
 Arranged in units that receive stimulation to contract individually
 Found in: iris and ciliary muscles of the eye; arrector pili muscles in skin; larger air
passageways in respiratory system; walls of larger arteries
 Degree of contraction depends on number of motor units activated, similar to
skeletal muscle

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Single-unit (visceral) smooth muscle
 Most common type
 Stimulated to contract in unison as cells
linked by gap junctions
 Form two or three sheets in wall of hollow
organ
 Locations include walls of digestive,
urinary, and reproductive tracts; portions
of respiratory tract; most blood vessels

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Stimulation of single-unit smooth muscle
 Occurs through varicosities (swellings of autonomic neurons) that contain
synaptic vessels with a neurotransmitter (ACh or norepinephrine)
 Receptors scattered across the sarcolemma with diffuse junctions
 Numerous smooth muscle cells stimulated simultaneously
 Stimulation spread from cell to cell via gap junctions so contraction is
synchronous

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 Test your understanding…

1. Where is smooth muscle located in the human body?

2. How are anchoring proteins and contractile proteins in smooth muscle cells
arranged

3. What is the specific role of the following structures within smooth muscle
cells: calmodulin, myosin light-chain kinase, and myosin light-chain
phosphatase?

4. What are the steps of smooth muscle contraction?

5. What unique characteristics of smooth muscle allow it to fulfill its functions?

Explain.

6. What are the various forms of stimulation for controlling smooth muscle?

7. Explain the stress-relaxation response of smooth muscle.

8. Explain why smooth muscle of the eye is multiunit smooth muscle and the
smooth muscle in the wall of digestive organs is single-unit smooth muscle.
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