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Chapter

Muscles and Muscle Tissue

 

Muscle Overview

•      The three types of muscle tissue are skeletal, cardiac, and smooth

•      These types differ in structure, location, function, and means of activation

Muscle Similarities

•      Skeletal and smooth muscle cells are elongated and are called muscle fibers

•      Muscle contraction depends on two kinds of myofilaments – actin and myosin

•      Muscle terminology is similar

•    Sarcolemma – muscle plasma membrane

•    Sarcoplasm – cytoplasm of a muscle cell

•    Prefixes – myo, mys, and sarco all refer to muscle

Skeletal Muscle Tissues

•      Packaged in skeletal muscles that attach to and cover the bony skeleton

•      Has obvious stripes called striations

•      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 over a range from a fraction of an ounce to over 70 pounds

Cardiac Muscle Tissue

•      Occurs only in the heart

•      Is striated like skeletal muscle but is not voluntary

•      Contracts at a fairly steady rate set by the heart’s pacemaker

•      Neural controls allow the heart to respond to changes in bodily needs

Smooth Muscle Tissue

•      Found in the walls of hollow visceral organs, such as the stomach, urinary bladder, and respiratory passages

•      Forces food and other substances through internal body channels

•      It is not striated and is involuntary

Muscle Function

•      Skeletal muscles are responsible for all locomotion

•      Cardiac muscle is responsible for coursing the blood through the body

•      Smooth muscle helps maintain blood pressure, and squeezes or propels substances (i.e., food, feces) through organs

•      Muscles also maintain posture, stabilize joints, and generate heat

Functional Characteristics of Muscles

•      Excitability, or irritability – the ability to receive and respond to stimuli

•      Contractility – the ability to shorten forcibly

•      Extensibility – the ability to be stretched or extended

•      Elasticity – the ability to recoil and resume the original resting length

Skeletal Muscle

•      Each muscle is a discrete organ composed of muscle tissue, blood vessels, nerve fibers, and connective tissue

•      The three connective tissue wrappings are:

•    Epimysium – an overcoat of dense regular CT that surrounds the entire muscle

•    Perimysium – fibrous CT that surrounds groups of muscle fibers called fascicles

•    Endomysium – fine sheath of CT composed of reticular fibers surrounding each       muscle fiber

Skeletal Muscle: Nerve and Blood Supply

•      Each muscle is served by one nerve, an artery, and one or more veins

•      Each skeletal muscle fiber is supplied with a nerve ending that controls contraction

•      Contracting fibers require continuous delivery of oxygen and nutrients via arteries

•      Wastes must be removed via veins

Skeletal Muscle: Attachments

•      Muscles span joints and are attached to bone in at least two places

•      When muscles contract the movable bone, the muscle’s insertion moves toward the immovable bone – the muscle’s origin

•      Muscles attach:

•    Directly – epimysium of the muscle is fused to the periosteum of a bone

•    Indirectly – CT wrappings extend beyond the muscle as a tendon or aponeurosis

Microscopic Anatomy of a Skeletal Muscle Fiber

•      Each fiber is a long, cylindrical cell with multiple nuclei just beneath the sarcolemma

•      Fibers are 10 to 100 mm in diameter, and up to hundreds of centimeters long

•      Each cell is a syncytium produced by fusion of embryonic cells

•      Sarcoplasm has numerous glycosomes and a unique oxygen-binding protein called myoglobin

•      Fibers contain the usual organelles, myofibrils, sarcoplasmic reticulum, and T tubules

Myofibrils

•      Myofibrils are densely packed, rodlike contractile elements

•      They make up most of the muscle volume

•      The arrangement of myofibrils within a fiber is such that a perfectly aligned repeating series of dark A bands and light I bands is evident

Sarcomeres

•      The smallest contractile unit of a muscle

•      The region of a myofibril between two successive Z discs

•      Composed of myofilaments made up of contractile proteins

•    Myofilaments are of two types – thick and thin

Myofilaments: Banding Pattern

•      Thick filaments – extend the entire length of an A band

•      Thin filaments – extend across the I band and partway into the A band

•      Z-disc – coin-shaped sheet of proteins (connectins) that anchors the thin filaments and connects myofibrils to one another

•      Thin filaments do not overlap thick filaments in the lighter H zone

•      M lines appear darker due to the presence of the protein desmin

Ultrastructure of Myofilaments: Thick Filaments

•      Thick filaments are composed of the protein myosin

•      Each myosin molecule has a rodlike tail and two globular heads

•    Tails – two interwoven, heavy polypeptide chains

•    Heads – two smaller, light polypeptide chains called cross bridges

Ultrastructure of Myofilaments: Thin Filaments

•      Thin filaments are chiefly composed of the protein actin

•      Each actin molecule is a helical polymer of globular subunits called G actin

•      The subunits contain the active sites to which myosin heads attach during contraction

•      Tropomyosin and troponin are regulatory subunits bound to actin

Arrangement of the Filaments in a Sarcomere

•      Longitudinal section within one sarcomere

Sarcoplasmic Reticulum (SR)

•      SR is an elaborate smooth endoplasmic reticulum that mostly runs longitudinally and surrounds each myofibril

•      Paired terminal cisternae form perpendicular cross channels

•      Functions in the regulation of intracellular calcium levels

•      Elongated tubes called T tubules penetrate into the cell’s interior at each A band–I band junction

•      T tubules associate with the paired terminal cisternae to form triads

T Tubules

•      T tubules are continuous with the sarcolemma

•      They conduct impulses to the deepest regions of the muscle

•      These impulses signal for the release of Ca2+ from adjacent terminal cisternae

Contraction of Skeletal Muscle Fibers

•      Contraction – refers to the activation of myosin’s cross bridges (force generating sites)

•      Shortening occurs when the tension generated by the cross bridge exceeds forces opposing shortening

•      Contraction ends when cross bridges become inactive, the tension generated declines, and relaxation is induced

Sliding Filament Mechanism of Contraction

•      Thin filaments slide past the thick ones so that the actin and myosin filaments overlap to a greater degree

•      In the relaxed state, thin and thick filaments overlap only slightly

•      Upon stimulation, myosin heads bind to actin and sliding begins

•      Each myosin head binds and detaches several times during contraction, acting like a ratchet to generate tension and propel the thin filaments to the center of the sarcomere

•      As this event occurs throughout the sarcomeres, the muscle shortens

Role of Ionic Calcium (Ca2+) in the Contraction Mechanism

•      At low intracellular Ca2+ concentration:

•    Tropomyosin blocks the binding sites on actin

•    Myosin cross bridges cannot attach to binding sites on actin

•    The relaxed state of the muscle is enforced

•      At higher intracellular Ca2+ concentrations:

•    Additional calcium binds to troponin (inactive troponin binds two Ca2+)

•    Calcium-activated troponin binds an additional two Ca2+ at a separate regulatory site

•      Calcium-activated troponin undergoes a conformational change

•      This change moves tropomyosin away from actin’s binding sites

•      Myosin head can now bind and cycle

•      This permits contraction (sliding of the thin filaments by the myosin cross bridges) to begin

Sequential Events of Contraction

•      Cross bridge attachment – myosin cross bridge attaches to actin filament

•      Working (power) stroke – myosin head pivots and pulls actin filament toward M line

•      Cross bridge detachment – ATP attaches to myosin head and the cross bridge detaches

•      “Cocking” of the myosin head – energy from hydrolysis of ATP cocks the myosin head into the high energy state

Regulation of Contraction

•      In order to contract, 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 trigger for contraction

•      Linking the electrical signal to the contraction is excitation-contraction coupling

Nerve Stimulus of Skeletal Muscle

•      Skeletal muscles are stimulated by motor neurons of the somatic nervous system

•      Axons of these neurons travel in nerves to muscle cells

•      Axons of motor neurons branch profusely as they enter muscles

•      Each axonal branch forms a neuromuscular junction with a single muscle fiber

Neuromuscular Junction

•      The neuromuscular junction is formed from:

•    Axonal endings, which have small membranous sacs (synaptic vesicles) that contain the neurotransmitter acetylcholine (ACh)

•    The motor end plate of a muscle, which is a specific part of the sarcolemma that contains ACh receptors that helps form the neuromuscular junction

•      Though exceedingly close, axonal ends and muscle fibers are always separated by a space called the synaptic cleft

•      When a nerve impulse reaches the end of an axon at the neuromuscular junction:

•    Voltage-regulated calcium channels open and allow Ca2+ to enter the axon

•    Ca2+ inside the axon terminal causes axonal vesicles to fuse with the axonal membrane

•    This fusion releases ACh into the synaptic cleft via exocytosis

•    ACh diffuses across the synaptic cleft to ACh receptors on the sarcolemma

•    Binding of ACh to its receptors initiates an action potential in the muscle

Action Potential

•      A transient depolarization event that includes polarity reversal of a sarcolemma (or nerve cell membrane) and the propagation of an action potential along the membrane

Action Potential: Electrical Conditions of a Polarized Sarcolemma

•      The outside (extracellular) face is positive, while the inside face is negative

•      This difference in charge is the resting membrane potential

•      The predominant extracellular ion is Na+

•      The predominant intracellular ion is K+

•      The sarcolemma is relatively impermeable to both ions

Action Potential: Depolarization and Generation of the Action Potential

•      An axonal terminal of a motor neuron releases ACh and causes a patch of the sarcolemma to become permeable to Na+ (sodium channels open)

•      Na+ enters the cell, and the resting potential is decreased (depolarization occurs)

•      If the stimulus is strong enough, an action potential is initiated

Action Potential: Propagation of the Action Potential

•      Polarity reversal of the initial patch of sarcolemma changes the permeability of the adjacent patch

•      Voltage-regulated Na+ channels now open in the adjacent patch causing it to depolarize

•      Thus, the action potential travels rapidly along the sarcolemma

•      Once initiated, the action potential is unstoppable, and ultimately results in the contraction of a muscle

Action Potential: Repolarization

•      Immediately after the depolarization wave passes, the sarcolemma permeability changes

•      Na+ channels close and K+ channels open

•      K+ diffuses from the cell, restoring the electrical polarity of the sarcolemma

•      Repolarization occurs in the same direction as depolarization, and must occur before the muscle can be stimulated again (refractory period)

•      The ionic concentration of the resting state is restored by the Na+-K+ pump

Destruction of Acetylcholine

•      ACh bound to ACh receptors is quickly destroyed by the enzyme acetylcholinesterase (AChE)

•      AChE activity prevents continued muscle fiber contraction in the absence of additional stimuli

Excitation-Contraction Coupling

•      Once generated, the action potential:

•    Is propagated along the sarcolemma

•    Travels down the T tubules

•    Triggers Ca2+ release from terminal cisternae

•      Ca2+ binds to troponin and causes:

•    The blocking action of tropomyosin to cease

•    Actin active binding sites to be exposed

•      Myosin cross bridges alternately attach and detach

•      Thin filaments move toward the center of the sarcomere

•      Hydrolysis of ATP powers this cycling process

•      Ca2+ is removed into the SR, tropomyosin blockage is restored, and the muscle fiber relaxes

Contraction of Skeletal Muscle (Organ Level)

•      Contraction of muscle fibers (cells) and muscles (organs) is similar

•      The two types of muscle contractions are:

•    Isometric contraction – increasing muscle tension (muscle does not shorten)

•    Isotonic contraction – decreasing muscle length (muscle shortens during contraction)

Motor Unit: The Nerve-Muscle Functional Unit

•      A motor unit is a motor neuron and all the muscle fibers it supplies

•      The number of muscle fibers per motor unit can vary from four to several hundred

•      Muscles that control fine movements (fingers, eyes) have small motor units

•      Large weight-bearing muscles (thighs, hips) have large motor units

•      Muscle fibers from a motor unit are spread throughout the muscle; therefore, contraction of a single motor unit causes weak contraction of the entire muscle

Muscle Twitch

•      A muscle twitch is the response of a muscle to a single brief threshold stimulus

•      The three phases of a muscle twitch are:

•    Latent period – first few milliseconds after stimulation when excitation-contraction coupling is taking place

•    Period of contraction – cross bridges actively form and the muscle shortens

•    Period of relaxation – Ca2+ is reabsorbed into the SR, and muscle tension goes to zero

Graded Muscle Response

•      Graded muscle responses are:

•    Variations in the degree of muscle contraction

•    Required for proper control of skeletal movement

•      Responses are graded by:

•    Changing the frequency of stimulation

•    Changing the strength of the stimulus

Muscle Response to Varying Stimuli

•      A single stimulus results in a single contractile response – a muscle twitch

•      Frequently delivered stimuli (muscle does not have time to completely relax) increases contractile force – wave summation

•      More rapidly delivered stimuli result in incomplete tetanus

•      If stimuli are given quickly enough, complete tetanus results

Muscle Response: Stimulation Strength

•      Threshold stimulus – the stimulus strength at which the first observable muscle contraction occurs

•      Beyond threshold, muscle contracts more vigorously as stimulus strength is increased

•      Force of contraction is precisely controlled by multiple motor unit summation

•      This phenomenon, called recruitment, brings more and more muscle fibers into play

Treppe: The Staircase Effect

•      Staircase – increased contraction in response to multiple stimuli of the same strength

•      Contractions increase because:

•    There is increasing availability of Ca2+ in the sarcoplasm

•    Muscle enzyme
systems become
more efficient
because heat is
increased as
muscle contracts

Muscle Tone

•      Muscle tone:

•    The constant, slightly contracted state of all muscles, which does not produce active movements

•    Keeps the muscles firm, healthy, and ready to respond to stimulus

•      Spinal reflexes account for muscle tone by:

•    Activating one motor unit and then another

•    Responding to activation of stretch receptors in muscles and tendons

Isotonic Contractions

•      In isotonic contractions, the muscle changes in length (decreasing the angle of the joint) and moves the load

•      The two types of isotonic contractions are concentric and eccentric

•    Concentric contractions – the muscle shortens and does work

•    Eccentric contractions – the muscle contracts as it lengthens

Isometric Contractions

•      Tension increases to the muscle’s capacity, but the muscle neither shortens nor lengthens

•      Occurs if the load is greater than the tension the muscle is able to develop

Muscle Metabolism: Energy for Contraction

•      ATP is the only source used directly for contractile activity

•      As soon as available stores of ATP are hydrolyzed (4-6 seconds), they are regenerated by:

•    The interaction of ADP with creatine phosphate (CP)

•    Anaerobic glycolysis and the Cori cycle

•    Aerobic respiration

Muscle Metabolism: Cori Cycle

•      When muscle contractile activity reaches 70% of maximum:

•    Bulging muscles compress blood vessels

•    Oxygen delivery is impaired

•    Pyruvic acid is converted into lactic acid

•      The lactic acid:

•    Diffuses into the bloodstream

•    Is picked up and used as fuel by the liver, kidneys, and heart

•    Is converted back into pyruvic acid by the liver

Muscle Fatigue

•      Muscle fatigue – the muscle is in a state of physiological inability to contract

•      Muscle fatigue occurs when:

•    ATP production fails to keep pace with ATP use

•    There is a relative deficit of ATP, causing contractures

•    Lactic acid accumulates in the muscle

•    Ionic imbalances are present

Oxygen Debt

•      Vigorous exercise causes dramatic changes in muscle chemistry

•      For a muscle to return to a resting state:

•    Oxygen reserves must be replenished

•    Lactic acid must be converted to pyruvic acid

•    Glycogen stores must be replaced

•    ATP and CP reserves must be resynthesized

•      Oxygen debt – the extra amount of O2 needed for the above restorative processes

Heat Production During Muscle Activity

•      Only 40% of the energy released in muscle activity is useful as work

•      The remaining 60% is given off as heat

•      Dangerous heat levels are prevented by radiation of heat from the skin and sweating

Force of Contraction

•      The force of contraction is affected by:

•    The number of muscle fibers contracting – the more motor fibers in a muscle, the stronger the contraction

•    The relative size of the muscle – the bulkier the muscle, the greater its strength

Force of Contraction

•    Series-elastic elements – the noncontractile structures in a muscle

•    Degree of muscle stretch – muscles contract strongest when muscle fibers are 80-120% of their normal resting length

Muscle Fiber Type: Functional Characteristics

•      Speed of contraction – determined by speed in which ATPases split ATP

•    The two types of fibers are slow and fast

•      ATP-forming pathways

•    Oxidative fibers – use aerobic pathways

•    Glycolytic fibers – use anaerobic glycolysis

•      These two criteria define three categories – slow oxidative fibers, fast oxidative fibers, and fast glycolytic fibers

Muscle Fibers: Speed of Contraction

•      Slow oxidative fibers contract slowly, have slow acting myosin ATPases, and are fatigue resistant

•      Fast oxidative fibers contract quickly, have fast myosin ATPases, and have moderate resistance to fatigue

•      Fast glycolytic fibers contract quickly, have fast myosin ATPases, and are easily fatigued

Smooth Muscle

•      Composed of spindle-shaped fibers with a diameter of 2-10 mm and lengths of several hundred mm

•      Lack the coarse CT sheaths of skeletal muscle, but have fine endomysium

•      Are organized into two layers (longitudinal and circular) of closely apposed fibers

•      Found in walls of hollow organs (except the heart)

•      Have essentially the same contractile mechanisms as skeletal muscle

Peristalsis

•      When the longitudinal layer contracts, the organ dilates and contracts

•      When the circular layer contracts, the organ elongates

•      Peristalsis – alternating contractions and relaxations of smooth muscles that mix and squeeze substances through the lumen of hollow organs

Innervation of Smooth Muscle

•      Smooth muscle lacks neuromuscular junctions

•      Innervating nerves have bulbous swellings called varicosities

•      Varicosities release neurotransmitters into wide synaptic clefts called diffuse junctions

Microscopic Anatomy of Smooth Muscle

•      SR is less developed than in skeletal muscle and lacks a specific pattern

•      T tubules are absent

•      Plasma membranes have pouchlike infoldings called caveoli

•      Ca2+ is sequestered in the extracellular space near the caveoli, allowing rapid influx when channels are opened

•      There are no visible striations and no sarcomeres

•      Thin and thick filaments are present

Proportion and Organization of Myofilaments in Smooth Muscle

•      Ratio of thick to thin filaments is much lower than in skeletal muscle

•      Thick filaments have heads along their entire length

•      There is no troponin complex

•      Thick and thin filaments are arranged diagonally, causing smooth muscle to contract in a corkscrew manner

•      Noncontractile intermediate filament bundles attach to dense bodies (analogous to Z discs) at regular intervals

Contraction of Smooth Muscle

•      Whole sheets of smooth muscle exhibit slow, synchronized contraction

•      They contract in unison, reflecting their electrical coupling with gap 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

Contractile Mechanism

•      Actin and myosin interact according to the sliding filament mechanism

•      The final trigger for contractions is a rise in intracellular Ca2+

•      Ca2+ is released from the SR and from the extracellular space

•      Ca2+ interacts with calmodulin and myosin light chain kinase to activate myosin

Role of Calcium Ion

•      Ca2+ binds to calmodulin and activates it

•      Activated calmodulin activates the kinase enzyme

•      Activated kinase transfers phosphate from ATP to myosin cross bridges

•      Phosphorylated cross bridges interact with actin to produce shortening

•      Smooth muscle relaxes when intracellular Ca2+ levels drop

Special Features of Smooth Muscle Contraction

•      Unique characteristics of smooth muscle include:

•    Smooth muscle tone

•    Slow, prolonged contractile activity

•    Low energy requirements

•    Response to stretch

Response to Stretch

•      Smooth muscles exhibits a phenomenon called stress-relaxation response in which:

•    Smooth muscle responds to stretch only briefly, and then adapts to its new length

•    The new length, however, retains its ability to contract

•    This enables organs such as the stomach and bladder to temporarily store contents

Hyperplasia

•      Certain smooth muscles can divide and increase their numbers by undergoing hyperplasia

•      This is shown by estrogen’s effect on the uterus

•    At puberty, estrogen stimulates the synthesis of more smooth muscle, causing the uterus to grow to adult size

•    During pregnancy, estrogen stimulates uterine growth to accommodate the increasing size of the growing fetus

Types of Smooth Muscle: Single Unit

•      The cells of single unit smooth muscle, commonly called visceral muscle:

•    Contract rhythmically as a unit

•    Are electrically coupled to one another via gap junctions

•    Often exhibit spontaneous action potentials

•    Are arranged in opposing sheets and exhibit stress-relaxation response

Types of Smooth Muscle: Multiunit

•      Multiunit smooth muscles are found:

•    In large airways to the lungs

•    In large arteries

•    In arrector pili muscles

•    Attached to hair follicles

•    In the internal eye muscles

Types of Smooth Muscle: Multiunit

•      Their characteristics include:

•    Rare gap junctions

•    Infrequent spontaneous depolarizations

•    Structurally independent muscle fibers

•    A rich nerve supply, which, with a number of muscle fibers, forms motor units

•    Graded contractions in response to neural stimuli

Muscular Dystrophy

•      Muscular dystrophy – group of inherited muscle-destroying diseases where muscles enlarge due to fat and connective tissue deposits, but muscle fibers atrophy

•      Duchenne muscular dystrophy (DMD)

•    Inherited, sex-linked disease carried by females and expressed in males (1/3500)

•    Diagnosed between the ages of 2-10

•    Victims become clumsy and fall frequently as their muscles fail

•    Progresses from the extremities upward, and victims die of respiratory failure in their 20s

•    Caused by a lack of the cytoplasmic protein dystrophin

•    There is no cure, but myoblast transfer therapy shows promise

Homeostatic Imbalance: Age Related

•      With age, connective tissue increases and muscle fibers decrease

•      Muscles become stringier and more sinewy

•      By age 80, 50% of muscle mass is lost (sarcopenia)

•      Regular exercise reverses sarcopenia

•      Aging of the cardiovascular system affects every organ in the body

•      Atherosclerosis may block distal arteries, leading to intermittent claudication and causing severe pain in leg muscles

Developmental Aspects

•      Muscle tissue develops from embryonic mesoderm called myoblasts

•      Multinucleated skeletal muscles form by fusion of myoblasts

•      The growth factor agrin stimulates the clustering of ACh receptors at newly forming motor end plates

•      As muscles are brought under the control of the somatic nervous system, the numbers of fast and slow fibers are also determined

•      Cardiac and smooth muscle myoblasts

•    Do not fuse but develop gap junctions at an early embryonic stage

Developmental Aspects: Regeneration

•      Cardiac and skeletal muscle become amitotic, but can lengthen and thicken

•      Myoblastlike satellite cells show very limited regenerative ability

•      Cardiac cells lack satellite cells

•      Smooth muscle has good regenerative ability

Developmental Aspects: After Birth

•      Muscular development reflects neuromuscular coordination

•      Development occurs head-to-toe, and proximal-to-distal

•      Peak natural neural control of muscles is achieved by midadolescence

•      Athletics and training can improve neuromuscular control

Developmental Aspects: Male and Female

•      There is a biological basis for greater strength in men than in women

•      Women’s skeletal muscle makes up 36% of their body mass

•      Men’s skeletal muscle makes up 42% of their body mass

•      These differences are due primarily to the male sex hormone testosterone

•      With more muscle mass, men are generally stronger than women

•      Body strength per unit muscle mass, however, is the same