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 myofilamentsactin 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 Tissue

§    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 ranging 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

Functional Characteristics of Muscle Tissue

§    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

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


Structure and Organization of Skeletal Muscle

Skeletal Muscle

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

§    The three connective tissue sheaths are:

§     Endomysium – fine sheath of connective tissue composed of reticular fibers surrounding each muscle fiber

§     Perimysium – fibrous connective tissue that surrounds groups of muscle fibers called fascicles

§     Epimysium – an overcoat of dense regular connective tissue that surrounds the entire muscle

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

§    Most skeletal 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 – connective tissue 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 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


§    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 rod-like 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

Triad Relationships

§    T tubules and SR provide tightly linked signals for muscle contraction

§    A double zipper of integral membrane proteins protrudes into the intermembrane space

§    T tubule proteins act as voltage sensors

§    SR foot proteins are receptors that regulate Ca2+ release from the SR cisternae

Sliding Filament Model 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


Skeletal Muscle 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 and 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


Destruction of Acetylcholine

§    ACh bound to ACh receptors is quickly destroyed by the enzyme acetylcholinesterase

§    This destruction prevents continued muscle fiber contraction in the absence of additional stimuli

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

Role of Acetylcholine (Ach)

§    ACh binds its receptors at the motor end plate

§    Binding opens chemically (ligand) gated channels

§    Na+ and K+ diffuse and the interior of the sarcolemma becomes less negative

§    This event is called depolarization



§    Initially, this is a local electrical event called end plate potential

§    Later, it ignites an action potential that spreads in all directions across the sarcolemma

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

Action Potential: Repolarization

§    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

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


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 formation – 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







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


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 during contraction)

§     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

§    There are three phases to a muscle twitch

§     Latent period

§     Period of contraction

§     Period of relaxation

Phases of a Muscle Twitch

§    Latent period – first few msec after stimulus; EC coupling taking place

§    Period of contraction – cross bridges from; muscle shortens

§    Period of relaxation – Ca2+ reabsorbed; muscle tension goes to zero


Muscle Twitch Comparisons


Graded Muscle Responses

§    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


Stimulus Intensity and Muscle Tension

Size Principle

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:

§     Is 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

§     Aerobic respiration

Muscle Metabolism: Anaerobic Glycolysis

§    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

§    Intense exercise produces rapid muscle fatigue (with rapid recovery)

§    Na+-K+ pumps cannot restore ionic balances quickly enough

§    Low-intensity exercise produces slow-developing fatigue

§    SR is damaged and Ca2+ regulation is disrupted

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 Muscle 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

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

Length Tension Relationships


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 Fiber Type: 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


Load and Contraction

Effects of Aerobic Exercise

§    Aerobic exercise results in an increase of:

§     Muscle capillaries

§     Number of mitochondria

§     Myoglobin synthesis

Effects of Resistance Exercise

§    Resistance exercise (typically anaerobic) results in:

§     Muscle hypertrophy

§     Increased mitochondria, myofilaments, and glycogen stores

The Overload Principle

§    Forcing a muscle to work promotes increased muscular strength

§    Muscles adapt to increased demands

§    Muscles must be overloaded to produce further gains

Smooth Muscle

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

§    Lack the coarse connective tissue sheaths of skeletal muscle, but have fine endomysium

§    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


§    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

Contraction 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 muscle 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


§    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

§    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



Developmental Aspects

§    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 in both sexes

Developmental Aspects: 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