Muscle Physiology

Muscle Tissue

Alternating contraction and relaxation of cells

Chemical energy changed into mechanical energy

Properties of Muscle Tissue

Excitability

  • respond to chemicals released from nerve cells
    •

    Conductivity

  • ability to propagate electrical signals over membrane
    •

    Contractility

  • ability to shorten and generate force

    • Extensibility

  • ability to be stretched without damaging the tissue
    •

    Elasticity

  • ability to return to original shape after being stretched
    •

    3 Types of Muscle Tissue

    Skeletal muscle

  • attaches to bone, skin or fascia
  • striated with light & dark bands visible with scope
  • voluntary control of contraction & relaxation
    •

    Cardiac muscle

  • striated in appearance
  • involuntary control
  • autorhythmic because of built in pacemaker
    •

    Smooth muscle

  • attached to hair follicles in skin
  • in walls of hollow organs
  • nonstriated in appearance
  • involuntary
    •

    Functions of Muscle Tissue

    Producing body movements

    Stabilizing body positions

    Regulating organ volumes

  • bands of smooth muscle called sphincters
    •

    Movement of substances within the body

  • blood, lymph, urine, air, food and fluids, sperm
    •

    Producing heat --Due to contractions of skeletal muscle

    Nerve and Blood Supply

    Each skeletal muscle is supplied by a nerve, artery and two veins.

    Each motor neuron supplies multiple muscle cells (neuromuscular junction)

    Each muscle cell is supplied by one motor neuron terminal branch and is in contact with one or two capillaries.

     

    Fusion of Myoblasts into Muscle Fibers

    Every mature muscle cell developed from 100 myoblasts that fuse together in the fetus. (multinucleated)

    Mature muscle cells can not divide

    Muscle growth is a result of cellular enlargement & not cell division

    Satellite cells retain the ability to regenerate new cells.

    Myofibrils & Myofilaments

    Muscle fibers are filled with threads called myofibrils separated by SR (sarcoplasmic reticulum)

    Myofilaments (thick & thin filaments) are the contractile proteins of muscle

    Thick & Thin Myofilaments

    Supporting proteins (M line, titin and Z disc help anchor the thick and thin filaments in place)

    T (transverse) tubules are invaginations of the sarcolemma into the center of the cell

  • filled with extracellular fluid
  • carry muscle action potentials down into the cell
    •

    Mitochondria

    Mitochondria lie in rows throughout the cell

  • Near the muscle proteins that use ATP during contraction
    •

    Sarcoplasmic Reticulum (SR)

    System of tubular sacs similar to smooth ER in nonmuscle cells

    Lateral sacs store Ca+2 in a relaxed muscle

    Release of Ca+2 triggers muscle contraction

    The Proteins of Muscle

    Myofibrils are built of 3 kinds of protein

  • Contractile proteins -Myosin and actin
  • Regulatory proteins which turn contraction on & off -
  • Troponin and tropomyosin
    •

    The Proteins of Muscle -- Myosin

    Thick filaments are composed of myosin

  • each molecule resembles two golf clubs twisted together
  • myosin heads (cross bridges) extend toward the thin filaments
    •

    The Proteins of Muscle -- Actin

    Thin filaments are made of actin, troponin, & tropomyosin

    The myosin-binding site on each actin molecule is covered by tropomyosin in relaxed muscle

    The thin filaments are held in place by Z discs. From one Z disc to the next is a sarcomere.

    The Proteins of Muscle -- Titin

    Titan anchors thick filament to the M line and the Z disc.

    The portion of the molecule between the Z disc and the end of the thick filament can stretch to 4 times its resting length and spring back unharmed.

    Role in recovery of the muscle from being stretched.

    Dystrophin

    Dystrophin links thin filaments to sarcolemma and transmits the tension generated to the tendon.

    Muscular Dystrophies

    Inherited, muscle-destroying diseases

    Absence of the protein, dystrophin

    Sarcolemma tears during muscle contraction

    Mutated gene is on X chromosome so problem is with males almost exclusively

    Appears by age 5 in males and by 12 may be unable to walk

    Degeneration of individual muscle fibers produces atrophy of the skeletal muscle

    Gene therapy is hoped for with the most common form = Duchenne muscular dystrophy

     

    Atrophy and Hypertrophy

    Atrophy

  • Wasting away of muscles
  • Caused by disuse (disuse atrophy) or severing of the nerve supply (denervation atrophy)
  • The transition to connective tissue can not be reversed
    •

    Hypertrophy

  • Increase in the diameter of muscle fibers
    •

    Resulting from very forceful, repetitive muscular activity and an increase in myofibrils, sarcoplasmic reticulum & mitochondria

    Exercise-Induced Muscle Damage

    Intense exercise can cause muscle damage

  • Electron micrographs reveal torn sarcolemmas, damaged myofibrils.
  • Blood tests reveal increased blood levels of myoglobin & creatine phosphate found only inside muscle cells
    •

    Delayed onset muscle soreness

  • 12 to 48 Hours after strenuous exercise
  • stiffness, tenderness and swelling due to microscopic cell damage
    •

    Neuromuscular Junction (NMJ) or Synapse

    End of axon nears the surface of a muscle fiber at its motor end plate region (remain separated by synaptic cleft or gap)

    Structures of NMJ Region

    Synaptic end bulbs are swellings of axon terminals
    End bulbs contain synaptic vesicles filled with acetylcholine (ACh)
    Each motor end plate membrane contains 30 million ACh receptors.

    Sliding Filament Mechanism Of Contraction

    Myosin cross bridges pull on thin filaments

    Thin filaments slide inward

    Z Discs come toward each other

    Sarcomeres shorten.

    The muscle fiber shortens.

    The muscle shortens

    Notice :Thick & thin filaments do not change in length

    How Does Contraction Occur?

    1. Nerve impulse reaches an axon terminal & synaptic vesicles release acetylcholine (ACh)

    2. ACh diffuses to receptors on the sarcolemma & Na+ channels open and Na+ rushes into the cell

    3. A muscle action potential spreads over sarcolemma and down into the transverse tubules. Voltage sensors at the sarcoplasmic reticulum stimulate the release of Ca2+ into the sarcoplasm

    4. Ca 2+binds with troponin. As a result, troponin rotates, along with the rest of the thin filament.

    5. This causes troponin-tropomyosin complex to move & reveal myosin binding sites on actin--the contraction cycle begins. Myosin binds to actin, creating a crossbridge.

    6. Powered by ATP, the myosin head becomes cocked, and pulls the actin fiber, along with the rest of the thin filament toward the middle of the sarcomere. This repeated action results in a muscle contraction

    7. The addition of a new ATP to myosin cross bridges detaches them from actin.

            -The cross bridges return to their original shape for a repeat of the power stroke cycle.

            -By the continued, repetition of the cycle, the "rowing" of the myosin cross bridges slide the actin toward the center of

                the sarcomere for muscle contraction.

            -However, for this repetition, calcium ions must be available.

    8. When it’s time for the muscle to relax, ATP is also required to detach a crossbridge. A third ATP molecule is required to detach Ca2+

    9. Relaxation of a skeletal muscle depends on the reuptake of calcium ions, from the cytosol into the SR.

    10.Cycle keeps repeating as long as there is ATP available and high Ca2+ level near thin filament

    Relaxation

    Acetylcholinesterase (AChE) breaks down ACh within the synaptic cleft

    Muscle action potential ceases

    Ca+2 release channels in SR close

    Active transport pumps Ca2+ back into storage in the lateral sacs of SR

    Calcium-binding protein (calsequestrin) helps hold Ca+2 in SR (Ca+2 concentration 10,000 times higher than in cytosol)

    Tropomyosin-troponin complex recovers binding site on the actin

    CURARE AND MUSCLE CONTRACTIONS

    Plant poison used in poison arrows

    Causes muscle paralysis by blocking ACh receptors

    Causes paralysis, death

    Used to relax muscles during surgery

    Myasthenia Gravis

    Weak muscle contractions because ACh removed too quickly

    Neostigmine (anticholinesterase agent)

  • blocks removal of ACh from receptors so strengthens weak muscle contractions of myasthenia gravis
  • also an antidote for curare after surgery is finished
    •

    Botulism

    Botulinum toxin blocks release of neurotransmitter at the NMJ so muscle contraction can not occur

  • bacteria found in improperly canned food
  • death occurs from paralysis of the diaphragm
    •

    Rigor Mortis

    Why does a body become stiff a few hours after death, then slowly relax?

    Rigor mortis is a state of muscular rigidity that begins 3-4 hours after death and lasts about 24 hours

    Calcium ions leak out of the SR

    Calcium binds to troponin complex, thin filaments rotate

    Actin binds to myosin

    Since ATP synthesis has ceased, crossbridges cannot detach from actin until proteolytic enzymes begin to digest the decomposing cells.

    The Motor Unit

    Motor unit = one somatic motor neuron & all the skeletal muscle cells (fibers) it stimulates

  • muscle fibers normally scattered throughout belly of muscle
  • One nerve cell supplies on average 150 muscle cells that all contract in unison.
  • Total strength of a contraction depends on how many motor units are activated & how large the motor units are
    •

    Twitch Contraction

    Brief contraction of all fibers in a motor unit in response to

  • single action potential in its motor neuron
  • electrical stimulation of the neuron or muscle fibers
    •

    Myogram = graph of a twitch contraction

  • the action potential lasts 1-2 msec
  • the twitch contraction lasts from 20 to 200 msec
    •

    Parts of a Twitch Contraction

    Latent Period--2msec

  • Ca+2 is being released from SR
    •

    Contraction Period

  • 10 to 100 msec
  • filaments slide past each other
    •

    Relaxation Period

  • 10 to 100 msec
  • active transport of Ca+2 into SR
    •

    Refractory Period

  • muscle can not respond and has lost its excitability
  • 5 msec for skeletal & 300 msec for cardiac muscle
    •

    Wave Summation
    If second stimulation applied after the refractory period but before complete muscle relaxation---second contraction is stronger than first

    Complete and Incomplete Tetanus

    Unfused/incomplete tetanus

  • if stimulate at 20-30 times/second, there will be only partial relaxation between stimuli
    •

    Fused/complete tetanus

  • if stimulate at 80-100 times/second, a sustained contraction with no relaxation between stimuli will result
    •

    Explanation of Summation & Tetanus

    Wave summation & both types of tetanus result from Ca+2 remaining in the sarcoplasm

    Force of 2nd contraction is easily added to the first, because the elastic elements remain partially contracted and do not delay the beginning of the next contraction

    Motor Unit Recruitment

    Motor units in a whole muscle fire asynchronously

  • some fibers are active others are relaxed
  • delays muscle fatigue so contraction can be sustained
    •

    Produces smooth muscular contraction

  • not series of jerky movements
    •

    Precise movements require smaller contractions

  • motor units must be smaller (less fibers/nerve)
    •

    Large motor units are active when large tension is needed

    Muscle Tone

    Involuntary contraction of a small number of motor units (alternately active and inactive in a constantly shifting pattern)

  • keeps muscles firm even though relaxed
  • does not produce movement

    • Essential for maintaining posture (head upright)

    Important in maintaining blood pressure

  • tone of smooth muscles in walls of blood vessels
    •

    Muscle Metabolism
    Production of ATP in Muscle Fibers

    Muscle uses ATP at a great rate when active

    Sarcoplasmic ATP only lasts for few seconds

    3 sources of ATP production within muscle

  • creatine phosphate
  • anaerobic cellular respiration
  • aerobic cellular respiration
    •

    Creatine Phosphate

    Excess ATP within resting muscle used to form creatine phosphate

    Creatine phosphate 3-6 times more plentiful than ATP within muscle

    Its quick breakdown provides energy for creation of ATP

    Sustains maximal contraction for 15 sec (used for 100 meter dash).

    Athletes tried creatine supplementation

  • gain muscle mass but shut down bodies own synthesis (safety?)
    •

    Anaerobic Cellular Respiration

    ATP produced from glucose breakdown into pyruvic acid during glycolysis

  • if no O2 present
  • pyruvic converted to lactic acid which diffuses into the blood
    •

    Glycolysis can continue anaerobically to provide ATP for 30 to 40 seconds of maximal activity (200 meter race)

    Aerobic Cellular Respiration

    ATP for any activity lasting over 30 seconds

  • if sufficient oxygen is available, pyruvic acid enters the mitochondria to generate ATP, water and heat
  • fatty acids and amino acids can also be used by the mitochondria
    •

    Provides 90% of ATP energy if activity lasts more than 10 minutes

    Muscle Fatigue

    Inability to contract after prolonged activity

  • central fatigue is feeling of tiredness and a desire to stop (protective mechanism)
  • depletion of creatine phosphate
  • decline of Ca+2 within the sarcoplasm
    •

    Factors that contribute to muscle fatigue

  • insufficient oxygen or glycogen
  • buildup of lactic acid and ADP
  • insufficient release of acetylcholine from motor neurons

    • Oxygen Consumption after Exercise

    Muscle tissue has two sources of oxygen.

  • diffuses in from the blood
  • released by myoglobin inside muscle fibers
    •

    Aerobic system requires O2 to produce ATP needed for prolonged activity

  • increased breathing effort during exercise

    • Recovery oxygen uptake

  • elevated oxygen use after exercise (oxygen debt)
  • lactic acid is converted back to pyruvic acid
  • elevated body temperature means all reactions faster
    •

    Variations in Skeletal Muscle Fibers

    Myoglobin, mitochondria and capillaries

  • Red muscle fibers
  •     more myoglobin, an oxygen-storing reddish pigment
  •     more capillaries and mitochondria

    •  

  • White muscle fibers
  • less myoglobin and less capillaries give fibers their pale color
    •

    Contraction and relaxation speeds vary

  • How fast myosin ATPase hydrolyzes ATP
    •

    Resistance to fatigue

  • different metabolic reactions used to generate ATP
    •

    Classification of Muscle Fibers

    Slow oxidative (slow-twitch)

  • Red in color (lots of mitochondria, myoglobin & blood vessels)
  • Prolonged, sustained contractions for maintaining posture
    •

    Fast oxidative-glycolytic (fast-twitch A)

  • red in color (lots of mitochondria, myoglobin & blood vessels)
  • split ATP at very fast rate; used for walking and sprinting
    •

    Fast glycolytic (fast-twitch B)

  • White in color (few mitochondria & BV, low myoglobin)
  • Anaerobic movements for short duration; used for weight-lifting
    •

    Fiber Types within a Whole Muscle

    Most muscles contain a mixture of all three fiber types

    Proportions vary with the usual action of the muscle

  • Neck, back and leg muscles have a higher proportion of postural, slow oxidative fibers
  • Shoulder and arm muscles have a higher proportion of fast glycolytic fibers
    •

    All fibers of any one motor unit are same.

    Different fibers are recruited as needed.

    Anabolic Steroids

    Similar to testosterone

    Increases muscle size, strength, and endurance

    Many very serious side effects

  • liver cancer
  • kidney damage
  • heart disease
  • mood swings
  • facial hair & voice deepening in females
  • atrophy of testicles & baldness in males
    •

    Regeneration of Muscle

    Skeletal muscle fibers cannot divide after 1st year

  • growth is enlargement of existing cells
  •     repair
  •     satellite cells & bone marrow produce some new cells
  •     if not enough numbers---fibrosis occurs most often
    •

    Cardiac muscle fibers cannot divide or regenerate

  • all healing is done by fibrosis (scar formation)
    •

    Smooth muscle fibers (regeneration is possible)

  • cells can grow in size (hypertrophy)
  • some cells (uterus) can divide (hyperplasia)
  • new fibers can form from stem cells in blood vessel walls
    •

    Aging and Muscle Tissue

    Skeletal muscle starts to be replaced by fat beginning at 30

  • "use it or lose it"
    •

    Slowing of reflexes & decrease in maximal strength

    Change in fiber type to slow oxidative fibers may be due to lack of use or may be result of aging

    Abnormal Contractions

    Spasm = involuntary contraction of single muscle

    Cramp = a painful spasm

    Tic = involuntary twitching of muscles normally under voluntary control--eyelid or facial muscles

    Tremor = rhythmic, involuntary contraction of opposing muscle groups

    Fasciculation = involuntary, brief twitch of a motor unit visible under the skin

    Smooth muscle composes the internal, contractile organs except the heart. The heart is composed of cardiac muscle.

    Smooth muscle can develop tension when it is stretched significantly. It inherently relaxes when stretched.

    Its contraction is slow and energy-efficient.

  • Single-unit smooth muscle can exist at a many lengths without a change in tension. It is well-suited for forming the walls of distensible, hollow organs.
    •

    A. Smooth Muscle Fibers

  • 1. Smooth muscle cells are elongated with tapered ends, lack striations, and have a relatively undeveloped sarcoplasmic reticulum.
    •

    B. Smooth Muscle Contraction

  • 1. The myosin-binding-to-actin mechanism is the mostly same for smooth muscles and skeletal muscles.
  • 2. Both acetylcholine (ACh) and norepinephrine stimulate and inhibit smooth muscle contraction, depending on the target muscle.
    •

                        3. Hormones can also stimulate or inhibit contraction.

  • 4. Smooth muscle is slower to contract and relax than is skeletal muscle, but can contract longer using the same amount of ATP.

    • ² Cardiac Muscle

    A. The mechanism of contraction in cardiac muscle is essentially the same as that for skeletal and smooth muscle, but with some differences.

    B. Cardiac muscle has transverse tubules that supply extra calcium, and can thus contract for longer periods.

    C. Cardiac muscle is self-exciting and rhythmic, and the whole structure contracts as a unit.