Chapter 1 A Perspective on Human Genetics

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Chapter 8 Muscle Physiology
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Outline

• Structure
• Contractile mechanisms
• Mechanics
• Control
• Other muscle types
• Smooth, cardiac

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Outline

• Structure
• Muscle fiber (from myoblasts)
• Myofibrils
• Thick and thin filaments (actin and myosin)
• A,H,M,I,Z
• Sarcomere
• Titin elasticity
• Cross bridges
• Myosin, Actin, tropomyosin, troponin

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Muscle

• Comprises largest group of tissues in body
• Three types of muscle
• Skeletal muscle
• Make up muscular system
• Cardiac muscle
• Found only in the heart
• Smooth muscle
• Appears throughout the body systems as components
  of hollow organs and tubes
• Classified in two different ways
• Striated or unstriated
• Voluntary or involuntary

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Categorization of Muscle
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Muscle

• Controlled muscle contraction allows
• Purposeful movement of the whole body or parts of
  the body
• Manipulation of external objects
• Propulsion of contents through various hollow
  internal organs
• Emptying of contents of certain organs to
  external environment

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Structure of Skeletal Muscle

• Muscle consists a number of muscle fibers lying
  parallel to one another and held together by
  connective tissue
• Single skeletal muscle cell is known as a muscle
  fiber
• Multinucleated
• Large, elongated, and cylindrically shaped
• Fibers usually extend entire length of muscle

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Muscle
Tendon
Muscle fiber (a single muscle cell)
Connective tissue
Fig. 8-2, p. 255
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Structure of Skeletal Muscle

• Myofibrils
• Contractile elements of muscle fiber
• Regular arrangement of thick and thin filaments
• Thick filaments myosin (protein)
• Thin filaments actin (protein)
• Viewed microscopically myofibril displays
  alternating dark (the A bands) and light bands
  (the I bands) giving appearance of striations

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Muscle fiber
Dark A band
Light I band
Myofibril
Fig. 8-2, p. 255
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Structure of Skeletal Muscle

• Sarcomere
• Functional unit of skeletal muscle
• Found between two Z lines (connects thin
  filaments of two adjoining sarcomeres)
• Regions of sarcomere
• A band
• Made up of thick filaments along with portions of
  thin filaments that overlap on both ends of thick
  filaments
• H zone
• Lighter area within middle of A band where thin
  filaments do not reach
• M line
• Extends vertically down middle of A band within
  center of H zone
• I band
• Consists of remaining portion of thin filaments
  that do not project into A band

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Z line
A band
I band
Portion of myofibril
M line
H zone
Sarcomere
Thick filament
A band
I band
Thin filament
Cross bridges
M line
H zone
Z line
Myosin
Actin
Thick filament
Thin filament
Fig. 8-2, p. 255
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I band
A band
I band
Cross bridge
Thick filament
Thin filament
Fig. 8-4, p. 256
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Structure of Skeletal Muscle

• Titin
• Giant, highly elastic protein
• Largest protein in body
• Extends in both directions from M line along
  length of thick filament to Z lines at opposite
  ends of sarcomere
• Two important roles
• Along with M-line proteins helps stabilize
  position of thick filaments in relation to thin
  filaments
• Greatly augments muscles elasticity by acting
  like a spring

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Myosin

• Component of thick filament
• Protein molecule consisting of two identical
  subunits shaped somewhat like a golf club
• Tail ends are intertwined around each other
• Globular heads project out at one end
• Tails oriented toward center of filament and
  globular heads protrude outward at regular
  intervals
• Heads form cross bridges between thick and thin
  filaments
• Cross bridge has two important sites critical to
  contractile process
• An actin-binding site
• A myosin ATPase (ATP-splitting) site

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Structure and Arrangement of Myosin Molecules
Within Thick Filament
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Actin

• Primary structural component of thin filaments
• Spherical in shape
• Thin filament also has two other proteins
• Tropomyosin and troponin
• Each actin molecule has special binding site for
  attachment with myosin cross bridge
• Binding results in contraction of muscle fiber

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Composition of a Thin Filament
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• Actin and myosin are often called contractile
  proteins. Neither actually contracts.
• Actin and myosin are not unique to muscle cells,
  but are more abundant and more highly organized
  in muscle cells.

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Tropomyosin and Troponin

• Often called regulatory proteins
• Tropomyosin
• Thread-like molecules that lie end to end
  alongside groove of actin spiral
• In this position, covers actin sites blocking
  interaction that leads to muscle contraction
• Troponin
• Made of three polypeptide units
• One binds to tropomyosin
• One binds to actin
• One can bind with Ca2

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Tropomyosin and Troponin

• Troponin
• When not bound to Ca2, troponin stabilizes
  tropomyosin in blocking position over actins
  cross-bridge binding sites
• When Ca2 binds to troponin, tropomyosin moves
  away from blocking position
• With tropomyosin out of way, actin and myosin
  bind, interact at cross-bridges
• Muscle contraction results

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Role of Calcium in Cross-Bridge Formation
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• Cross-bridge interaction between actin and myosin
  brings about muscle contraction by means of the
  sliding filament mechanism.

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Outline

• Contractile mechanisms
• Sliding filament mechanism (Theory)
• Ca dependence
• Power stroke
• T tubules
• Ca release
• Lateral sacs, foot proteins, ryanodine receptors,
  dihydropyradine receptors
• Cross bridge cycling
• Rigor mortis, relaxation, latent period

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Sliding Filament Mechanism

• Increase in Ca2 starts filament sliding
• Decrease in Ca2 turns off sliding process
• Thin filaments on each side of sarcomere slide
  inward over stationary thick filaments toward
  center of A band during contraction
• As thin filaments slide inward, they pull Z lines
  closer together
• Sarcomere shortens

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Basic 4 steps
Fig. 8-9, p. 260
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Detailed steps Hydrolysis of ATP pivots
head Release of ADP and Pi cocks head
Fig. 8-13, p. 263
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Calcium Release in Excitation-Contraction Coupling
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Power Stroke

• Activated cross bridge bends toward center of
  thick filament, rowing in thin filament to
  which it is attached
• Sarcoplasmic reticulum releases Ca2 into
  sarcoplasm
• Myosin heads bind to actin
• Myosin heads swivel toward center of sarcomere
  (power stroke)
• ATP binds to myosin head and detaches it from
  actin

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Power Stroke

• Hydrolysis of ATP transfers energy to myosin head
  and reorients it
• Contraction continues if ATP is available and
  Ca2 level in sarcoplasm is high

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Sliding Filament Mechanism

• All sarcomeres throughout muscle fibers length
  shorten simultaneously
• Contraction is accomplished by thin filaments
  from opposite sides of each sarcomere sliding
  closer together between thick filaments

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Changes in Banding Pattern During Shortening
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Relaxation

• Depends on reuptake of Ca2 into sarcoplasmic
  reticulum (SR)
• Acetylcholinesterase breaks down ACh at
  neuromuscular junction
• Muscle fiber action potential stops
• When local action potential is no longer present,
  Ca2 moves back into sarcoplasmic reticulum

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T tubule
Terminal button
Surface membrane of muscle cell
Acetylcholine- gated cation channel
Lateral sacs of sarcoplasmic reticulum
Acetylcholine
Troponin
Tropomyosin
Actin
Cross-bridge binding
Myosin cross bridge
Fig. 8-12, p. 262
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T Tubules and Sarcoplasmic Reticulum
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Sarcoplasmic Reticulum

• Modified endoplasmic reticulum
• Consists of fine network of interconnected
  compartments that surround each myofibril
• Not continuous but encircles myofibril throughout
  its length
• Segments are wrapped around each A band and each
  I band
• Ends of segments expand to form saclike regions
  lateral sacs (terminal cisternae)

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Transverse Tubules

• T tubules
• Run perpendicularly from surface of muscle cell
  membrane into central portions of the muscle
  fiber
• Since membrane is continuous with surface
  membrane action potential on surface membrane
  also spreads down into T-tubule
• Spread of action potential down a T tubule
  triggers release of Ca2 from sarcoplasmic
  reticulum into cytosol

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Relationship Between T Tubule and Adjacent
Lateral Sacs of Sarcoplasmic Reticulum
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Outline

• Mechanics
• Tendons
• Twitch
• Motor unit
• Motor unit recruitment
• Fatigue
• Asynchronous recruitment
• Twitch, tetanus, summation
• Muscle length, isometric, isotonic
• Tension, origin, insertion

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Skeletal Muscle Mechanics

• Muscle consists of groups of muscle fibers
  bundled together and attached to bones
• Connective tissue covering muscle divides muscle
  internally into bundles
• Connective tissue extends beyond ends of muscle
  to form tendons
• Tendons attach muscle to bone

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Muscle Contractions

• Contractions of whole muscle can be of varying
  strength
• Twitch
• Brief, weak contraction
• Produced from single action potential
• Too short and too weak to be useful
• Normally does not take place in body
• Two primary factors which can be adjusted to
  accomplish gradation of whole-muscle tension
• Number of muscle fibers contracting within a
  muscle
• Tension developed by each contracting fiber

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Motor Unit Recruitment

• Motor unit
• One motor neuron and the muscle fibers it
  innervates
• Number of muscle fibers varies among different
  motor units
• Number of muscle fibers per motor unit and number
  of motor units per muscle vary 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

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Motor Unit Recruitment

• Asynchronous recruitment of motor units helps
  delay or prevent fatigue
• Factors influencing extent to which tension can
  be developed
• Frequency of stimulation
• Length of fiber at onset of contraction
• Extent of fatigue
• Thickness of fiber

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Schematic Representation of Motor Units in
Skeletal Muscle
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Twitch Summation and Tetanus

• Twitch summation
• Results from sustained elevation of cytosolic
  calcium
• Tetanus
• Occurs if muscle fiber is stimulated so rapidly
  that it does not have a chance to relax between
  stimuli
• Contraction is usually three to four times
  stronger than a single twitch

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Summation and Tetanus
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Muscle Tension

• Tension is produced internally within sarcomeres
• Tension must be transmitted to bone by means of
  connective tissue and tendons before bone can be
  moved (series-elastic component)
• Muscle typically attached to at least two
  different bones across a joint
• Origin
• End of muscle attached to more stationary part of
  skeleton
• Insertion
• End of muscle attached to skeletal part that
  moves

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Fig. 8-17, p. 268
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Types of Contraction

• Two primary types
• Isotonic
• Muscle tension remains constant as muscle changes
  length
• Isometric
• Muscle is prevented from shortening
• Tension develops at constant muscle length

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Contraction-Relaxation Steps Requiring ATP

• Splitting of ATP by myosin ATPase provides energy
  for power stroke of cross bridge
• Binding of fresh molecule of ATP to myosin lets
  bridge detach from actin filament at end of power
  stroke so cycle can be repeated
• Active transport of Ca2 back into sarcoplasmic
  reticulum during relaxation depends on energy
  derived from breakdown of ATP

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Energy Sources for Contraction

• Transfer of high-energy phosphate from creatine
  phosphate to ADP
• First energy storehouse tapped at onset of
  contractile activity
• Oxidative phosphorylation (citric acid cycle and
  electron transport system
• Takes place within muscle mitochondria if
  sufficient O2 is present
• Glycolysis
• Supports anaerobic or high-intensity exercise

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Muscle Fatigue

• Occurs when exercising muscle can no longer
  respond to stimulation with same degree of
  contractile activity
• Defense mechanism that protects muscle from
  reaching point at which it can no longer produce
  ATP
• Underlying causes of muscle fatigue are unclear

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Central Fatigue

• Occurs when CNS no longer adequately activates
  motor neurons supplying working muscles
• Often psychologically based
• Mechanisms involved in central fatigue are poorly
  understood

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Outline

• Other types
• Fibers
• Fast
• slow
• Oxidative
• glycolytic
• Smooth, cardiac
• Creatine phosphate
• Oxidative phosphorulation
• Aerobic, myoglobin
• Glycolysis
• Anaerobic, lactic acid

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Major Types of Muscle Fibers

• Classified based on differences in ATP hydrolysis
  and synthesis
• Three major types
• Slow-oxidative (type I) fibers
• Fast-oxidative (type IIa) fibers
• Fast-glycolytic (type IIx) fibers

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Characteristics of Skeletal Muscle Fibers
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Control of Motor Movement

• Three levels of input control motor-neuron output
• Input from afferent neurons
• Input from primary motor cortex
• Input from brain stem

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Muscle Spindle Structure

• Consist of collections of specialized muscle
  fibers known as intrafusal fibers
• Lie within spindle-shaped connective tissue
  capsules parallel to extrafusal fibers
• Each spindle has its own private efferent and
  afferent nerve supply
• Play key role in stretch reflex

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Muscle Spindle Function
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Capsule
Alpha motor neuron axon
Intrafusal (spindle) muscle fibers
Gamma motor neuron axon
Contractile end portions of intrafusal fiber
Noncontractile central portion of
intrafusal fiber
Secondary (flower-spray) endings of
afferent fibers
Primary (annulospiral) endings of afferent fibers
Extrafusal (ordinary) muscle fibers
Fig. 8-24, p. 283
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Stretch Reflex

• Primary purpose is to resist tendency for
  passive stretch of extensor muscles by
  gravitational forces when person is standing
  upright
• Classic example is patellar tendon, or knee-jerk
  reflex

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Patellar Tendon Reflex
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Outline

• Other muscle types
• Smooth, cardiac
• This information is covered in detail in the
  lecture on the heart.

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Smooth Muscle

• Found in walls of hollow organs and tubes
• No striations
• Filaments do not form myofibrils
• Not arranged in sarcomere pattern found in
  skeletal muscle
• Spindle-shaped cells with single nucleus
• Cells usually arranged in sheets within muscle
• Have dense bodies containing same protein found
  in Z lines

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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

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Stepped art
Fig. 8-28, p. 288
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Calcium Activation of Myosin Cross Bridge in
Smooth Muscle
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Comparison of Role of Calcium In Bringing About
Contraction in SmoothMuscle and Skeletal Muscle
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Smooth Muscle

• Two major types
• Multiunit smooth muscle
• Single-unit smooth muscle

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Multiunit Smooth Muscle

• Neurogenic
• Consists of discrete units that function
  independently of one another
• Units must be separately stimulated by nerves to
  contract
• Found
• In walls of large blood vessels
• In large airways to lungs
• In muscle of eye that adjusts lens for near or
  far vision
• In iris of eye
• At base of hair follicles

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Single-unit Smooth Muscle

• Self-excitable (does not require nervous
  stimulation for contraction)
• Also called visceral smooth muscle
• Fibers become excited and contract as single unit
• Cells electrically linked by gap junctions
• Can also be described as a functional syncytium
• Contraction is slow and energy-efficient
• Well suited for forming walls of distensible,
  hollow organs

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Cardiac Muscle

• Found only in walls of heart
• Striated
• Cells are interconnected by gap junctions
• Fibers are joined in branching network
• Innervated by autonomic nervous system