Muscle Physiology

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Muscle Physiology
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Muscle Tissue

• Muscle accounts for nearly half of the bodys
  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

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Skeletal Muscle

• Skeletal muscles attach to and cover the bony
  skeleton
• Is controlled voluntarily (i.e., by conscious
  control)
• Contracts rapidly but tires easily
• Is responsible for overall body motility
• Is extremely adaptable and can exert forces
  ranging from a fraction of an ounce to over 70
  pounds
• Has obvious stripes called striations
• Each muscle cell is multinucleated

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Microscopic Anatomy - Skeletal Muscle Fiber

• Sarcoplasm contains glycosomes (granules of
  glycogen) and the oxygen-binding protein called
  myoglobin
• In addition to the typical organelles, fibers
  have
• Sarcoplasmic reticulum
• T tubules - modifications of the sarcolemma
• Myofibrils
• 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 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) bands and light I
  (isotropic) bands

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Myofibrils - Striations

• The 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
• I band has a darker midline called the Z disc (or
  Z line)

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Sarcomere

• Smallest contractile unit of a muscle
• Myofibril region between two successive Z discs,
  has a central A band and partial (half) I bands
  at each end

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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

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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
Figure 12-3cf
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Arrangement of Filaments in a Sarcomere
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Sarcoplasmic Reticulum (SR)

• SR - an elaborate, smooth ER that surrounds each
  myofibril. Perpendicular (transverse) channels
  at the A band - I band junction are the Terminal
  Cisternae (Lateral Sacs) SR regulates
  intracellular Ca2
• T tubules at each A band/I band junction -
  continuous with the sarcolemma. Conduct
  electrical impulses to the throughout cell (every
  sarcomere) - signals for the release of Ca2 from
  adjacent terminal cisternae

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Triad 2 terminal cisternae and 1 T tubule

• T tubules and SR provide tightly linked signals
  for muscle contraction
• Interaction of integral membrane proteins (IMPs)
  from T tubules and SR

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Interaction of T-Tubule Proteins and SR Foot
Proteins

• T tubule proteins (Dihydropyridine) act as
  voltage sensors
• SR foot proteins are (ryanodine) receptors that
  regulate Ca2 release from the SR cisternae
• Action potential in t-tubule alters conformation
  of DHP receptor
• DHP receptor opens Ca2 release channels in
  sarcoplasmic reticulum and Ca2 enters cytoplasm

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Sliding Filament Model of Contraction

• Contraction refers to the activation of myosins
  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
• Actin filaments slide past the myosin filaments
  so that the actin and myosin filaments overlap to
  a greater degree (the actin filaments are moved
  toward the center of the sarcomere, Z lines
  become closer)

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Sliding Filament Model of Contraction
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Sliding Filament Model of Contraction
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Skeletal Muscle Contraction

• For contraction to occur, a skeletal muscle must
• Be stimulated by a nerve ending
• Propagate an electrical current, or action
  potential, along its sarcolemma
• Have a rise in intracellular Ca2 levels, the
  final stimulus for contraction
• The series of events linking the action potential
  to contraction is called excitation-contraction
  coupling

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Depolarization and Generation of an AP

• The sarcolemma, like other plasma membranes is
  polarized. There is a potential difference
  (voltage) across the membrane
• When Ach binds to its receptors on the motor end
  plate, chemically (ligand) gated ion channels in
  the receptors open and allow Na and K to move
  across the membrane, resulting in a transient
  change in membrane potential - Depolarization
• End plate potential - a local depolarization that
  creates and spreads an action potential across
  the 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.

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Regulatory Role of Tropomyosin and Troponin
Figure 12-10b, steps 15
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Excitation-Contraction Coupling
Figure 12-11a, steps 12
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Excitation-Contraction Coupling

• 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)

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Excitation-Contraction Coupling

• Some of the Ca2 binds to troponin, troponin
  changes shape and causes tropomysin to move which
  exposes the active 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)

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Excitation-Contraction Coupling

• 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

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The Molecular Basis of Contraction
Figure 12-9
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Sequential Events of Contraction
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Motor Unit

• 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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Electrical and Mechanical Events in Muscle
Contraction

• A twitch is a single contraction-relaxation cycle

Figure 12-12
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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

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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

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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

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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
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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
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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

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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
• When muscle tension develops, but the load is not
  moved (muscle does not shorten) the contraction
  is called Isometric
• If muscle tension overcomes (moves) the load and
  the muscle shortens, the contraction is called
  Isotonic

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Isometric Contractions
No change in overall muscle length
In isometric contractions, increasing muscle
tension (force) is measured
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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

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Isotonic Contraction
This illustrates a concentric isotonic contraction
In isotonic contractions, the amount of
shortening (distance in mm) is measured
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Energy Sources for Contraction

• ATP is the only energy source that is used
  directly for contractile activity
• As soon as available ATP is hydrolyzed (4-6
  seconds), it is regenerated by three pathways
• 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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CP-ADP Reaction

• Transfer of energy as a phosphate group is moved
  from CP to ADP the reaction is catalyzed by the
  enzyme creatine kinase
• Creatine phosphate ADP ? creatine ATP
• Stored ATP and CP provide energy for maximum
  muscle power for 10-15 seconds

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Anaerobic Glycolysis

• Glucose is broken down into pyruvic acide to
  yield 2 ATP
• When oxygen demand cannot be met, pyruvic acid is
  converted into lactic acid
• Lactic acid diffuses into the bloodstream can
  be used as energy source by the liver, kidneys,
  and heart
• Can be converted back into pyruvic acid, glucose,
  or glycogen by the liver

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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
• Glucose O2 ? CO2 H2O ATP

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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 energy stores glycogen
• When no ATP is available, contractures
  (continuous contraction) may result because cross
  bridges are unable to detach

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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, and are fatigue
  resistant
• Fast oxidative fibers (Type IIA)- contract
  quickly, have fast myosin ATPases, and have
  moderate resistance to fatigue
• Fast glycolytic fibers (Type IIB)- contract
  quickly, have fast myosin ATPases, and are easily
  fatigued

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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

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Smooth Muscle

• 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

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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
• Have dense bodies containing same protein found
  in Z lines

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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 activates mysoin kinase
• Myosin kinase phosphorylates myosin
• Myosin can now bind with actin

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Smooth Muscle Contraction
Figure 12-28, steps 15
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Comparison of Role of Calcium In Bringing About
Contraction in SmoothMuscle and Skeletal Muscle
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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 not voluntary
• Contracts at a fairly steady rate set by the
  hearts pacemaker
• Neural controls allow the heart to respond to
  changes in bodily needs