PHYSIOLOGY

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PHYSIOLOGY
DEN 1003 ANP 1001
Prepared by:
Dr. D. Boyd
MUSCULOSKELETAL
PHYSIOLOGY
• Muscle cells are specialized for contraction
• Action potential transmitted along the
sarcolemma (muscle cell membrane) 
activates contractile mechanism
• 3 Types of Muscles:
– Skeletal (striated; striped under
microscope)
• Under voluntary control
• Rapid acting
MUSCULOSKELETAL
PHYSIOLOGY
• 3 Types of Muscles: (cont)
– Smooth (blood vessel walls & internal
organs)
• Involuntary (inherent rhythmic
contraction)
• Slow acting
– Cardiac: striated, features of both skeletal,
& smooth muscle
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
• Composed of many parallel muscle fibers
(myofibers)
• Myofibers:
– Run length of muscle
– Terminate in tendons that attach fiber to
Skeletal system.
– Multi-nucleated structure
– Surrounded by sarcolemma
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
• A. Structural Changes During Contraction
• 1. Shortening:
– Result from increase in extent of thin-thick
filament overlap
– Thin filament (Actin) slide over 
Thick filament (Myosin)
center of sarcomere (unit of myofiber)
– “sliding filament mechanism”
– Sarcomere length decreases
– Length of filaments do not change
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
Z
line
Sarcomere
A band (dark)
Actin
Contraction
Myosin
I band
(light)
Z
Relaxed State line
H band
I & H bands shorten
Contracted State
Contraction of Sarcomere
MUSCULOSKELETAL
PHYSIOLOGY
Molecular Aspects of Contraction
Actin
Pi
ADP-Pi
ATP
Myosin
ATP
ADP
ATP
THE CONTRACTILE CYCLE (mechanochemical coupling)
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
• 2. Molecular Aspects of Contraction
• Upon stimulation of myofiber, myosin heads
with (ADP + Pi) connect with actin filaments
• Actin-myosin complex form (ADP + Pi released)
• Actin-myosin bond broken (ATP added)
• Cycle repeated
• CLINICAL CORRELATION
• No ATP, myosin heads can NOT release,
leads to stable actin-myosin complex  rigor
mortis
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
• B. Excitation-Contraction Coupling
• Action Potential generated by motor neuron
initiates mechanical
contraction
• AP transmitted along muscle membrane,
down T tubule to sarcoplasmic reticulum
• Cytoplasmic Ca++ released
• Ca++ contact myosin & actin filaments
• Site on actin expose that binds to myosin
• Ca++-ATPase (sarcoplasmic reticulum) depletes
Ca
MUSCULOSKELETAL
PHYSIOLOGY
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SKELETAL MUSCLE
C. Summary of Contraction Sequence
AP get to end of axon
ACh released at neuromuscular junction
ACh diffuse across gap
Nicotinic ACh receptor at end-plates
react with ACh
• Muscle cell membrane depolarized
• AP travel along muscle cell membrane
• T tubule depolarization, travel to
sarcoplasmic reticulum  Ca++ release
into cytoplasm
MUSCULOSKELETAL
PHYSIOLOGY
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SKELETAL MUSCLE
C. Summary of Contraction Sequence (cont)
Ca++ binds to troponin-tropomyosin
Myosin heads bind to actin
Myosin-ATPase activated
Cross-bridges attach & detach
Myosin & actin slide past each other
Sarcoplasmic reticulum pumps Ca++
back into lumen
• Ca++ removed from tropin-tropomyosin `
complex & actin-myosin interaction inhihited
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
• Single Action Potential  muscle twitch,
brief contraction followed by relaxation
• Twitch starts 2 msec after depolarization of
membrane begins, i.e. during re-polarization.
Action Potential
Start of
Electrical
Response
Contraction Time
Peak of Contraction
Muscle Twitch
Relative Timing of AP &
Muscle Contraction
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
• CLINICAL CORRELATION:
• Ca++ re-uptake mechanism of the
sarcoplasmic reticulum = Ryanodine
Receptor
• In some people this receptor is blocked by
general anesthetic with succinylcholine.
• Ca++ is NOT taken up quickly enough and
muscles
“overcontract”,
generating
enormous amounts of heat (malignant
hyperthermia), which can be fatal if not
treated with dantroline.
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
• D. Muscle Mechanics
• Most physical activity include both isometric
& isotonic contractions
• 1. Definitions:
– Isometric contraction:
• Both ends of muscle are fixed
• No change in length during contraction
• Tension (force) increases
• E.g. pushing against a wall
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
• D. Muscle Mechanics
• 1. Definitions: (cont)
– Isotonic contraction
• Muscle shorten during contraction
• Tension (force) remains constant
–E.g. lifting weights
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
• D. Muscle Mechanics
• 1. Definitions: (cont)
– Dynamic contraction
• Muscle length & force change during
contraction
• Muscle may shorten = concentric
contraction
• Muscle may be pulled out by load =
eccentric contraction
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
• D. Muscle Mechanics
• 2. Length-Tension Relationship
• Tension developed in an isometric contraction varies
with the initial length of the muscle fiber.
• There an optimal length at which a muscle is able to
develop maximum tension.
Tmax
Tension
Passive Tension
Active Tension
Lopt Length of Muscle
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
• NOTE:
• Sarcomeres (in series) of the same myofibril
do NOT generate additive force
• To generate more force, more fibers must be
recruited (in parallel)
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
• Isotonic Contraction
• The velocity at which the muscle contracts
varies inversely with the load it lifts.
• At 0 load there is rapid but finite velocity of
shortening
• With increasing load the velocity approaches
0.
• At 0 velocity contraction becomes
iosometric.
• This point = maximum active force of muscle
MUSCULOSKELETAL
PHYSIOLOGY
• SKELETAL MUSCLE
• Isotonic Contraction
Isometric Contraction Maximum Force
Force
0
Initial Velocity of Contraction
Force-Velocity Relationship in Skeletal Muscle
MUSCULOSKELETAL
PHYSIOLOGY
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E. Types of Skeletal Muscle Fibers
Property
Fast Twitch Slow Twitch
& Type
Color
White
Red
SR & T tubules
Many
Few
Myosin ATPase
High
Low
Mitrochondria
Few (short,
Many
(sustained
rapid mov’ts contractions)
• SR = sarcoplasmic reticulum
MUSCULOSKELETAL
PHYSIOLOGY
• E. Types of Skeletal Muscle Fibers (cont)
• 1. Fast Twitch (Type 11)
• White
Few fibers per motor unit
• Large diameter
No myoglobin
• Use glycolysis to generate energy,
function under anaerobic conditions
• Adapted for rapid contraction
• Enable fine, careful movements (e.g.
contraction of extraocular muscles of
Eye, & superior head of Temporalis
muscle)
MUSCULOSKELETAL
PHYSIOLOGY
• E. Types of Skeletal Muscle Fibers (cont)
• 2. Slow-twitch(Type 1)(muscles of
mastication)
• Red due presence of myoglobin
• Small diameter fibers
• Less sarcoplasmic reticulum & Ttubules
• Smaller motor end plates
• Slow to contract, adapted for long,
sustained contraction
• Oxidative metabolism used for energy
• Large number of mitrochondria & more
blood supply
MUSCULOSKELETAL
PHYSIOLOGY
• IN SUMMARY
• Fast-twitch (Type 11) vs Slow-twitch (Type 1)
• Think of chicken:
– White meat (white muscle) (Type 11) found
in breast, used for intermittent flapping
of wings.
– Dark meat (red muscle) (Type 1)found in
thighs, used for stained maintenance
of posture.
MUSCULOSKELETAL
PHYSIOLOGY
• F. Motor Units
• Consists of all the muscles innervated by a
single alpha motor nerve axon
• Excitation of motor neuron result in
contraction of all fibers in the motor unit
• Each muscle fibers of a given motor unit is of
the same muscle type
• If motor nerve is destroyed , all muscle fibers
innervate by that neuron atrophy
(e.g. spinal injury)
MUSCULOSKELETAL
PHYSIOLOGY
• Twitch & Tetanus
• 1. Single Twitch
• Elastic elements (tendons, connective tissue)
within muscle & between the muscles & its
attachments represent “slack” that must be
stretched before the active tension generated
by the muscle can be exerted.
– This time delay for elastic stretch is
enough for the active twitch to decline.
– Therefore peak tension is never exerted by
a single twitch.
MUSCULOSKELETAL
PHYSIOLOGY
Twitch Amplitude & Relative Timing & Amplitude for
Force Generated
100
Tetanus
Peak
Tension
(%)
50
Unfused Tetanus (clonus)
25
Single Twitch
0.5
1.0
Response to 2 stimuli
1.5
2
Time
Tetanus
MUSCULOSKELETAL
PHYSIOLOGY
• Tetanus
• Summation (fusion) of Contractions
• Result from high frequency neural
stimulation over short period of time
• Cause partly because elastic elements have
been fully stretched from early contractions
hence maximum tension develop wit no time
for relaxation of fibers
• Caused by increased Ca++ availability over
repeated contractions
MUSCULOSKELETAL
PHYSIOLOGY
• G. Skeletal Muscle Muscle Receptors:
• Two types:
– Muscle spindle (embedded within group of
fibers)
– Golgi Tendon Organs (arranged in tendon
in series with myofibers)
MUSCULOSKELETAL
PHYSIOLOGY
• G. Skeletal Muscle Receptors
• 1. Muscle Spindle
Gamma Efferent
Primary
1a Afferent
11 Afferent
Nuclear Bag Fiber
Poles
Nuclear Chain Fiber
Intrafusal Fiber & Innervation
MUSCULOSKELETAL
PHYSIOLOGY
• G. Skeletal Muscle Receptors
• 1. Muscle Spindle (cont)
• Intrafusal fibers = small muscle fibers
innervated by small gamma motor
neurons
• Primary (annulospiral) type 1a Afferent
fibers, rapid conducting, innervate center of
both the Nuclear Bag & Nuclear Chain
• Secondary (flower-spray) type 11 Afferent
fibers, slow conducting, innervate Nuclear
Chain only
MUSCULOSKELETAL
PHYSIOLOGY
1. Muscle Spindle (cont)
• Motor innervation of Intrafusal fibers = small
slow conducting gamma Efferent fibers
• Stretching muscle causes stretching &
deformation of Muscle Spindle, which result
in volley of impulses in Primary Afferent
neurons, that synapse directly on alpha
motor neurons innervating extrafusal fibers
of the muscle in which the Spindle is
embedded.
E.g. contraction of the
Quadriceps muscle is elicited when the
Patella Tendon is tapped leading to the “
knee-jerk reflex”
MUSCULOSKELETAL
PHYSIOLOGY
1. Muscle Spindle (cont)
Primary Afferent type 1a neurons discharge
rapidly during the lengthening of the
muscle, therefore respond to length as well
a velocity of stretch of the muscle.
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Secondary type 11 neurons discharge
rapidly during the entire period of stretch of
the muscle, therefore respond mainly to
length.
MUSCULOSKELETAL
PHYSIOLOGY
1. Muscle Spindle (cont)
• SUMMARY
• Muscle Spindle (intrafusal fibers) contain:
– A contractile element innervated by
gamma motor neurons
– A non-contractile element enveloped by
stretch-sensitive afferent neurons
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Muscle stretch causes an increase rate of
firing from Spindle afferents, resulting in
increased firing of alpha motor neurons to
cause muscle contraction
MUSCULOSKELETAL
PHYSIOLOGY
• G. Skeletal Muscle Receptors (cont)
• 2. Golgi Tendon Organs
• Arranged in series with a discrete number of
skeletal muscle fibers
• When skeletal contracts, the tendon in which
the muscle inserts lengthens & stretches the
nerve ending of the afferent fibers, causing
them to fire.
MUSCULOSKELETAL
PHYSIOLOGY
• G. Skeletal Muscle Receptors (cont)
• 2. Golgi Tendon Organs (cont)
• Supplied by 1b afferent fibers, which
synapse on inhibitory inter-neurons, which
synapse with alpha motor neurons, which
inhibit contraction which is protective.
• SUMMARY
• Muscle Spindle sense muscle length
• Golgi tendon Organs sense muscle tension
MUSCULOSKELETAL
PHYSIOLOGY
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SMOOTH MUSCLE
Regulate internal environment of the body
Smaller in size & uni-nucleated
Have fewer myofibrils & less organized
Dense bodies on cell membrane & inside
cytoplasm act as site of actin filament
insertion
• Have much less myosin
• Have no T tubules & little sarcoplasmic
reticulum.
• Ca++ enter from extracellular fluid
MUSCULOSKELETAL
PHYSIOLOGY
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SMOOTH MUSCLE
Contraction & Relaxation:
Occur slowly
Involve overlap of actin & myosin
Thin filaments inserted into Dense bodies are
pulled closer together by bridging myosin
units.
• Dense bodies on cell surface are pulled
together so that cell is deformed 
contraction.
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