physiology den 1003 anp 1001 prepared by: dr. d. boyd

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


• 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


• 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


• 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


• SKELETAL MUSCLE

Sarcomere

Actin

Myosin

H band Z line

I band (light)

A band (dark)

Relaxed State Contracted StateContraction of Sarcomere

Contraction

I & H bands shorten

Z line


Actin

Myosin

ADP-Pi

Pi

ADP

ATP

ATP

Molecular Aspects of Contraction

ATP

THE CONTRACTILE CYCLE (mechanochemical coupling)


• 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


• 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 • Filaments return to inactivated state


• 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


• 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


• 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

Muscle Twitch

Contraction Time

Relative Timing of AP & Muscle Contraction

Start of Electrical Response

Peak of Contraction


• 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.


• 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


• SKELETAL MUSCLE• D. Muscle Mechanics• 1. Definitions: (cont)

– Isotonic contraction• Muscle shorten during contraction • Tension (force) remains constant

–E.g. lifting weights


• 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


• 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.

Passive Tension

Active Tension

Lopt Length of Muscle

Tmax

Tension


• 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)


• 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


• SKELETAL MUSCLE• Isotonic Contraction

Force

Initial Velocity of Contraction

Force-Velocity Relationship in Skeletal Muscle

Isometric Contraction Maximum Force

0


• 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


• 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)


• 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


• 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.


• 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)


• 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.


Tetanus

Unfused Tetanus (clonus)

Response to 2 stimuliSingle Twitch

0.5 1.0 1.5 2

Peak Tension (%) 25

50

Time

Tetanus

Twitch Amplitude & Relative Timing & Amplitude for Force Generated100


• 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


• G. Skeletal Muscle Muscle Receptors:• Two types:

– Muscle spindle (embedded within group of

fibers)

– Golgi Tendon Organs (arranged in tendon in series with

myofibers)


• G. Skeletal Muscle Receptors• 1. Muscle Spindle

Gamma Efferent

Primary 1a Afferent11 Afferent

Nuclear Chain Fiber

Nuclear Bag Fiber

Intrafusal Fiber & Innervation

Poles


• 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


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”


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.

• Secondary type 11 neurons discharge rapidly during the entire period of stretch of the muscle, therefore respond mainly to length.


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

• Muscle stretch causes an increase rate of firing from Spindle afferents, resulting in increased firing of alpha motor neurons to cause muscle contraction


• 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.


• 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


• 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


• 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.

physiology den 1003 anp 1001 prepared by: dr. d. boyd

Documents

smooth muscle slide

muscle membrane

myosin actin slide past

filament actin slide

length of muscle

actin myosinatpase

sarcolemma slide

cytoplasm slide