LECTURE OUTLINE CH9

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 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

§ 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 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

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

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

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

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

§ 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