Chapter 9 AMP

Terminologies: Myo, mys, and sarco are prefixes for

muscle

Three types of muscle tissue

Skeletal

– Cardiac

– Smooth

Only skeletal and smooth muscle cells are elongated and referred to as

muscle fibers

Skeletal muscle

Skeletal muscle tissue is packaged into skeletal muscles: organs that are

attached to bones and skin

– Skeletal muscle fibers are longest of all muscle and have striations (stripes)

– Also called voluntary muscle: can be consciously controlled

– Contract rapidly; tire easily; powerful

– Key words for skeletal muscle: skeletal, striated, and voluntary

Cardiac muscle

Cardiac muscle tissue is found only in heart

 Makes up bulk of heart walls

– Striated

– Involuntary: cannot be controlled consciously

 Contracts at steady rate due to heart’s own pacemaker, but nervous system

can increase rate

– Key words for cardiac muscle: cardiac, striated, and involuntary

Smooth muscle

Smooth muscle tissue: found in walls of hollow organs

 Examples: stomach, urinary bladder, and airways

– Not striated

– Involuntary: cannot be controlled consciously

– Key words for smooth muscle: visceral, nonstriated and involuntary

All muscles share four main characteristics

Excitability (responsiveness): ability to receive and respond to stimuli

– Contractility: ability to shorten forcibly when stimulated

– Extensibility: ability to be stretched

– Elasticity: ability to recoil to resting length

Muscle Functions

• Four important functions

1. Produce movement: responsible for all locomotion and manipulation

 Example: walking, digesting, pumping blood

2. Maintain posture and body position

3. Stabilize joints

4. Generate heat as they contract

Skeletal muscle is an organ made up of different tissues with three features

nerve and blood supply, connective tissue sheaths, and attachments

Nerve and Blood Supply

Each muscle receives a nerve, artery, and veins

– Consciously controlled skeletal muscle has nerves supplying every fiber to control

activity

• Contracting muscle fibers require huge amounts of oxygen and nutrients

– Also need waste products removed quickly

Connective Tissue Sheaths

Each skeletal muscle, as well as each muscle fiber, is covered in connective tissue

• Support cells and reinforce whole muscle

• Sheaths from external to internal:

– Epimysium: dense irregular connective tissue surrounding entire muscle; may

blend with fascia

– Perimysium: fibrous connective tissue surrounding fascicles (groups of muscle

fibers)

– Endomysium: fine areolar connective tissue surrounding each muscle fiber

Attachments

Muscles span joints and attach to bones

• Muscles attach to bone in at least two places

– Insertion: attachment to movable bone

– Origin: attachment to immovable or less movable bone

• Attachments can be direct or indirect

– Direct (fleshy): epimysium fused to periosteum of bone or perichondrium of

cartilage

– Indirect: connective tissue wrappings extend beyond muscle as ropelike tendon or

sheetlike aponeurosis

Muscle Fiber Microanatomy and Sliding

Filament Model

Skeletal muscle fibers are long, cylindrical cells that contain multiple nuclei

• Sarcolemma: muscle fiber plasma membrane

• Sarcoplasm: muscle fiber cytoplasm

• Contains many glycosomes for glycogen storage, as well as myoglobin for O2 storage

• Modified organelles

– Myofibrils

– Sarcoplasmic reticulum

– T tubules

Myofibrils

are densely packed, rodlike elements

– Single muscle fiber can contain 1000s

– Accounts for ~80% of muscle cell volume

• Myofibril features

– Striations

– Sarcomeres

– Myofilaments

– Molecular composition of myofilaments

Striations

stripes formed from repeating series of dark and light bands along length of

each myofibril

– A bands: dark regions

 H zone: lighter region in middle of dark A band

– M line: line of protein (myomesin) that bisects H zone vertically

– I bands: lighter regions

 Z disc (line): coin-shaped sheet of proteins on midline of light I band

Sarcomere

Smallest contractile unit (functional unit) of muscle fiber

– Contains A band with half of an I band at each end

 Consists of area between Z discs

– Individual sarcomeres align end to end along myofibril, like boxcars of train

Myofilaments

Orderly arrangement of actin and myosin myofilaments within sarcomere

– Actin myofilaments: thin filaments

 Extend across I band and partway in A band

 Anchored to Z discs

– Myosin myofilaments: thick filaments

 Extend length of A band

 Connected at M line

– Sarcomere cross section shows hexagonal arrangement of one thick filament

surrounded by six thin filaments

Molecular composition of myofilaments

Thick filaments: composed of protein myosin that contains two heavy and four light

polypeptide chains

 Heavy chains intertwine to form myosin tail

 Light chains form myosin globular head

– During contraction, heads link thick and thin filaments together, forming

cross bridges

 Myosins are offset from each other, resulting in staggered array of heads at

different points along thick filament

Molecular composition of myofilaments (cont.)

Thin filaments: composed of fibrous protein actin

 Actin is polypeptide made up of kidney-shaped G actin (globular) subunits

– G actin subunits bears active sites for myosin head attachment during

contraction

 G actin subunits link together to form long, fibrous F actin (filamentous)

 Two F actin strands twist together to form a thin filament

– Tropomyosin and troponin: regulatory proteins bound to actin

Other proteins help form the structure of the myofibril

 Elastic filament: composed of protein titin

– Holds thick filaments in place; helps recoil after stretch; resists excessive

stretching

 Dystrophin

– Links thin filaments to proteins of sarcolemma

 Nebulin, myomesin, C proteins bind filaments or sarcomeres together

– Maintain alignment of sarcomere

Duchenne muscular dystrophy (DMD)

is most common and serious form of muscular

dystrophies, muscle-destroying diseases that generally appear during childhood

• Inherited as a sex-linked recessive disease, so almost exclusively in males (1 in 3600

births)

• Appears between 2 and 7 years old when boy becomes clumsy and falls frequently

• Disease progresses from extremities upward, finally affecting head, chest muscles, and

cardiac muscle.

• With supportive care, people with DMD can live into 30s and beyond

Homeostatic Imbalance

Caused by defective gene for dystrophin, a protein that links thin filaments to

extracellular matrix and helps stabilize sarcolemma

• Sarcolemma of DMD patients tear easily, allowing entry of excess calcium which

damages contractile fibers

• Inflammation follows and regenerative capacity is lost resulting in increased apoptosis of

muscle cells and drop in muscle mass

chest muscles, and cardiac muscle. The weakness continues to

• progress, but with supportive care, DMD patients are living into

• their 30s and beyond.

Sarcoplasmic reticulum

network of smooth endoplasmic reticulum tubules

surrounding each myofibril

– Most run longitudinally

– Terminal cisterns form perpendicular cross channels at the A–I band junction

– SR functions in regulation of intracellular Ca2+ levels

– Stores and releases Ca2+

T tubule

Tube formed by protrusion of sarcolemma deep into cell interior

 Increase muscle fiber’s surface area greatly

 Lumen continuous with extracellular space

 Allow electrical nerve transmissions to reach deep into interior of each muscle

fiber

– Tubules penetrate cell’s interior at each A–I band junction between terminal

cisterns

 Triad: area formed from terminal cistern of one sarcomere, T tubule, and

terminal cistern of neighboring sarcomere

Triad relationships

T tubule contains integral membrane proteins that protrude into intermembrane

space (space between tubule and muscle fiber sarcolemma)

 Tubule proteins act as voltage sensors that change shape in response to an

electrical current

– SR cistern membranes also have integral membrane proteins that protrude into

intermembrane space

 SR integral proteins control opening of calcium channels in SR cisterns

When an electrical impulse passes by, T tubule proteins change shape, causing

SR proteins to change shape, causing release of calcium into cytoplasm

Contraction

the activation of cross bridges to generate force

• Shortening occurs when tension generated by cross bridges on thin filaments exceeds

forces opposing shortening

• Contraction ends when cross bridges become inactive

In the relaxed state, thin and thick filaments overlap only slightly at ends of A band

Sliding filament model of contraction

states that during contraction, thin filaments

slide past thick filaments, causing actin and myosin to overlap more

– Neither thick nor thin filaments change length, just overlap more

• When nervous system stimulates muscle fiber, myosin heads are allowed to bind to

actin, forming cross bridges, which cause sliding (contraction) process to begin

Sliding Filament Model of Contraction

Cross bridge attachments form and break several times, each time pulling thin filaments

a little closer toward center of sarcome in a ratcheting action

– Causes shortening of muscle fiber

• Z discs are pulled toward M line

• I bands shorten

• Z discs become closer

• H zones disappear

• A bands move closer to each other

Background and Overview

Decision to move is activated by brain, signal is transmitted down spinal cord to motor

neurons which then activate muscle fibers

• Neurons and muscle cells are excitable cells capable of action potentials

– Excitable cells are capable of changing resting membrane potential voltages

• AP crosses from neuron to muscle cell via the neurotransmitter acetylcholine (ACh)

Ion Channels

Play the major role in changing of membrane potentials

– Two classes of ion channels:

 Chemically gated ion channels – opened by chemical messengers such as

neurotransmitters

– Example: ACh receptors on muscle cells

 Voltage-gated ion channels – open or close in response to voltage changes in

membrane potential

Anatomy of Motor Neurons and the Neuromuscular Junction

Skeletal muscles are stimulated by somatic motor neurons

– Axons (long, threadlike extensions of motor neurons) travel from central nervous

system to skeletal muscle

– Each axon divides into many branches as it enters muscle

– Axon branches end on muscle fiber, forming neuromuscular junction or motor

end plate

 Each muscle fiber has one neuromuscular junction with one motor neuron

Axon terminal

(end of axon) and muscle fiber are separated by gel-filled space

called synaptic cleft

– Stored within axon terminals are membrane-bound synaptic vesicles

 Synaptic vesicles contain neurotransmitter acetylcholine (ACh)

– Infoldings of sarcolemma, called junctional folds, contain millions of ACh

receptors

– NMJ consists of axon terminals, synaptic cleft, and junctional folds

The Big Picture

Four steps must occur for skeletal muscle to contract:

1. Events at neuromuscular junction

2. Muscle fiber excitation

3. Excitation-contraction coupling

4. Cross bridge cycling

Events at the Neuromuscular Junction

1. AP arrives at axon terminal

2. Voltage-gated calcium channels open, calcium enters motor neuron

3. Calcium entry causes release of ACh neurotransmitter into synpatic cleft

4. ACh diffuses across to ACh receptors (Na+ chemical gates) on sarcolemma

5. ACh binding to receptors, opens gates, allowing Na+ to enter resulting in end plate

potential

6. Acetylcholinesterase degrades ACh

Homeostatic Imbalance 9.2

Many toxins, drugs, and diseases interfere with events at the neuromuscular junction

– Example: myasthenia gravis: disease characterized by drooping upper eyelids,

difficulty swallowing and talking, and generalized muscle weakness

– Involves shortage of Ach receptors because person’s ACh receptors are attacked

by own antibodies

– Suggests this is an autoimmune disease

Generation of an Action Potential Across the

Sarcolemma

Resting sarcolemma is polarized, meaning a voltage exists across membrane

– Inside of cell is negative compared to outside

• Action potential is caused by changes in electrical charges

• Occurs in three steps

1. Generation of end plate potential

2. Depolarization

3. Repolarization

End plate potential

ACh released from motor neuron binds to ACh receptors on sarcolemma

– Causes chemically gated ion channels (ligands) on sarcolemma to open

– Na+ diffuses into muscle fiber

 Some K+ diffuses outward, but not much

– Because Na+ diffuses in, interior of sarcolemma becomes less negative (more

positive)

– Results in local depolarization called end plate potential

2. Depolarization

generation and propagation of an action potential (AP)

– If end plate potential causes enough change in membrane voltage to reach critical

level called threshold, voltage-gated Na+ channels in membrane will open

– Large influx of Na+ through channels into cell triggers AP that is unstoppable and

will lead to muscle fiber contraction

– AP spreads across sarcolemma from one voltage-gated Na+ channel to next one in

adjacent areas, causing that area to depolarize

3. Repolarization

restoration of resting conditions

– Na+ voltage-gated channels close, and voltage-gated K+ channels open

– K+ efflux out of cell rapidly brings cell back to initial resting membrane voltage

– Refractory period: muscle fiber cannot be stimulated for a specific amount of

time, until repolarization is complete

– Ionic conditions of resting state are restored by Na+-K+ pump

 Na+ that came into cell is pumped back out, and K+ that flowed outside is

pumped back into cell

Excitation-contraction (E-C) coupling

events that transmit AP along sarcolemma

(excitation) are coupled to sliding of myofilaments (contraction)

• AP is propagated along sarcolemma and down into T tubules, where voltage-sensitive

proteins in tubules stimulate Ca2+ release from SR

– Ca2+ release leads to contraction

• AP is brief and ends before contraction is seen

Muscle Fiber Contraction: Cross Bridge

Cycling

At low intracellular Ca2+ concentration:

– Tropomyosin blocks active sites on actin

– Myosin heads cannot attach to actin

– Muscle fiber remains relaxed

• Voltage-sensitive proteins in T tubules change shape, causing sarcoplasmic reticulum

(SR) to release Ca2+ to cytosol

At higher intracellular Ca2+ concentrations, Ca2+ binds to troponin

• Troponin changes shape and moves tropomyosin away from myosin-binding sites

• Myosin heads is then allowed to bind to actin, forming cross bridge

• Cycling is initiated, causing sarcomere shortening and muscle contraction

• When nervous stimulation ceases, Ca2+ is pumped back into SR, and contraction ends

Four steps of the cross bridge cycle

1. Cross bridge formation: high-energy myosin head attaches to actin thin filament

active site

2. Working (power) stroke: myosin head pivots and pulls thin filament toward M line

3. Cross bridge detachment: ATP attaches to myosin head, causing cross bridge to

detach

4. Cocking of myosin head: energy from hydrolysis of ATP “cocks” myosin head

into high-energy state

 This energy will be used for power stroke in next cross bridge cycle

Rigor mortis

3–4 hours after death, muscles begin to stiffen

 Peak rigidity occurs about 12 hours postmortem

– Intracellular calcium levels increase because ATP is no longer being synthesized,

so calcium cannot be pumped back into SR

 Results in cross bridge formation

– ATP is also needed for cross bridge detachment

 Results in myosin head staying bound to actin, causing constant state of

contraction

– Muscles stay contracted until muscle proteins break down, causing myosin to

release

Whole Muscle Contraction

Same principles apply to contraction of both single fibers and whole muscles

• Contraction produces muscle tension, the force exerted on load or object to be moved

• Contraction may/may not shorten muscle

– Isometric contraction: no shortening; muscle tension increases but does not

exceed load

– Isotonic contraction: muscle shortens because muscle tension exceeds load

Force and duration of contraction vary in response to stimuli of different frequencies and

intensities

• Each muscle is served by at least one motor nerve

– Motor nerve contains axons of up to hundreds of motor neurons

– Axons branch into terminals, each of which forms NMJ with single muscle fiber

• Motor unit is the nerve-muscle functional unit

Motor unit

consists of the motor neuron and all muscle fibers (four to several hundred) it

supplies

– Smaller the fiber number, the greater the fine control

• Muscle fibers from a motor unit are spread throughout the whole muscle, so stimulation

of a single motor unit causes only weak contraction of entire muscle

Muscle twitch

simplest contraction resulting from a muscle fiber’s response to a single

action potential from motor neuron

– Muscle fiber contracts quickly, then relaxes

• Twitch can be observed and recorded as a myogram

– Tracing: line recording contraction activity

Three phases of muscle twitch

Latent period: events of excitation-contraction coupling

 No muscle tension seen

– Period of contraction: cross bridge formation

 Tension increases

– Period of relaxation: Ca2+ reentry into SR

 Tension declines to zero

• Muscle contracts faster than it relaxes

Differences in strength and duration of twitches are due to variations in metabolic

properties and enzymes between muscles

Graded Muscle Responses

Normal muscle contraction is relatively smooth, and strength varies with needs

– A muscle twitch is seen only in lab setting or with neuromuscular problems, but not

in normal muscle

• Graded muscle responses vary strength of contraction for different demands

– Required for proper control of skeletal movement

• Responses are graded by:

– Changing frequency of stimulation

– Changing strength of stimulation

Muscle response to changes in stimulus frequency

– Single stimulus results in single contractile response (i.e., muscle twitch)

Muscle response to changes in stimulus frequency (cont.)

Wave (temporal) summation results if two stimuli are received by a muscle in

rapid succession

 Muscle fibers do not have time to completely relax between stimuli, so twitches

increase in force with each stimulus

 Additional Ca2+ that is released with second stimulus stimulates more

shortening

Muscle response to changes in stimulus frequency (cont.)

– If stimuli frequency increases, muscle tension reaches near maximum

 Produces smooth, continuous contractions that add up (summation)

 Further increase in stimulus frequency causes muscle to progress to

sustained, quivering contraction referred to as unfused (incomplete) tetanus

Graded Muscle Responses (5 of 7)

• Muscle response to changes in stimulus frequency

If stimuli frequency further increase, muscle tension reaches maximum

 Referred to as fused (complete) tetanus because contractions “fuse” into one

smooth sustained contraction plateau

 Prolonged muscle contractions lead to muscle fatigue

Muscle response to changes in stimulus strength

– Recruitment (or multiple motor unit summation): stimulus is sent to more

muscle fibers, leading to more precise control

– Types of stimulus involved in recruitment:

 Subthreshold stimulus: stimulus not strong enough, so no contractions seen

 Threshold stimulus: stimulus is strong enough to cause first observable

contraction

 Maximal stimulus: strongest stimulus that increases maximum contractile

force

– All motor units have been recruited

Recruitment works on size principle

 Motor units with smallest muscle fibers are recruited first

 Motor units with larger and larger fibers are recruited as stimulus intensity

increases

 Largest motor units are activated only for most powerful contractions

 Motor units in muscle usually contract asynchronously

– Some fibers contract while others rest

– Helps prevent fatigue

Muscle Tone

Constant, slightly contracted state of all muscles

• Due to spinal reflexes

– Groups of motor units are alternately activated in response to input from stretch

receptors in muscles

• Keeps muscles firm, healthy, and ready to respond

Isotonic and Isometric Contractions

Isotonic contractions: muscle changes in length and moves load

– Isotonic contractions can be either concentric or eccentric:

 Concentric contractions: muscle shortens and does work

– Example: biceps contract to pick up a book

 Eccentric contractions: muscle lengthens and generates force

– Example: laying a book down causes biceps to lengthen while generating

a force

Isometric contractions

– Load is greater than the maximum tension muscle can generate, so muscle neither

shortens nor lengthens

Electrochemical and mechanical events are same in isotonic or isometric contractions,

but results are different

– In isotonic contractions, actin filaments shorten and cause movement

– In isometric contractions, cross bridges generate force, but actin filaments do not

shorten

 Myosin heads “spin their wheels” on same actin- binding site

Energy for Contraction and ATP

Providing Energy for Contraction

ATP supplies the energy needed for the muscle fiber to:

– Move and detach cross bridges

– Pump calcium back into SR

– Pump Na+ out of and K+ back into cell after excitation-contraction coupling

• Available stores of ATP depleted in 4–6 seconds

• ATP is the only source of energy for contractile activities; therefore it must be

regenerated quickly

Providing Energy for Contraction

ATP is regenerated quickly by three mechanisms:

– Direct phosphorylation of ADP by creatine phosphate (CP)

– Anaerobic pathway: glycolysis and lactic acid formation

– Aerobic pathway

Direct phosphorylation of ADP by creatine phosphate (CP)

– Creatine phosphate is a unique molecule located in muscle fibers that donates a

phosphate to ADP to instantly form ATP

 Creatine kinase is enzyme that carries out transfer of phosphate

 Muscle fibers have enough ATP and CP reserves to power cell for about 15

seconds

Creatine phosphate + ADP → creatine + ATP

Anaerobic pathway: glycolysis and lactic acid formation

ATP can also be generated by breaking down and using energy stored in glucose

 Glycolysis: first step in glucose breakdown

– Does not require oxygen

– Glucose is broken into 2 pyruvic acid molecules

– 2 ATPs are generated for each glucose broken down

 Low oxygen levels prevent pyruvic acid from entering aerobic respiration

phase

Normally, pyruvic acid enters mitochondria to start aerobic respiration phase;

however, at high intensity activity, oxygen is not available

 Bulging muscles compress blood vessels, impairing oxygen delivery

– In the absence of oxygen, referred to as anaerobic glycolysis, pyruvic acid is

converted to lactic acid

Lactic acid

 Diffuses into bloodstream

 Used as fuel by liver, kidneys, and heart

 Converted back into pyruvic acid or glucose by liver

– Anaerobic respiration yields only 5% as much ATP as aerobic respiration, but

produces ATP 2½ times faster

Aerobic Respiration

Produces 95% of ATP during rest and light-to-moderate exercise

 Slower than anaerobic pathway

– Consists of series of chemical reactions that occur in mitochondria and require

oxygen

 Breaks glucose into CO2, H2O, and large amount ATP (32 can be produced)

– Fuels used include glucose from glycogen stored in muscle fiber, then bloodborne

glucose, and free fatty acids

 Fatty acids are main fuel after 30 minutes of exercise

Energy systems used during sports

– Aerobic endurance

 Length of time muscle contracts using aerobic pathways

– Light-to-moderate activity, which can continue for hours

– Anaerobic threshold

 Point at which muscle metabolism converts to anaerobic pathway

Muscle Fatigue

Fatigue is the physiological inability to contract despite continued stimulation

• Possible causes include:

– Ionic imbalances can cause fatigue

 Levels of K+, Na+ and Ca2+ can change disrupting membrane potential of

muscle cell

– Increased inorganic phosphage (Pi) from CP and ATP breakdown may interfere with

calcium release from SR or hamper power

Decreased ATP and increased magnesium

 As ATP levels drop, magnesium levels increase and this can interfere with

voltage sensitive T tubule proteins

– Decreased glycogen

• Lack of ATP is rarely a reason for fatigue, except in severely stressed muscles

Excess Postexercise Oxygen Consumption

For a muscle to return to its pre-exercise state:

– Oxygen reserves are replenished

– Lactic acid is reconverted to pyruvic acid

– Glycogen stores are replaced

– ATP and creatine phosphate reserves are resynthesized

• All replenishing steps require extra oxygen, so this is referred to as excess

postexercise oxygen consumption (EPOC)

– Formerly referred to as “oxygen debt”

Force of Muscle Contractions

Force of contraction depends on number of cross bridges attached, which is affected by

four factors:

1. Number of muscle fibers stimulated (recruitment): the more motor units

recruited, the greater the force.

2. Relative size of fibers: the bulkier the muscle, the more tension it can develop

 Muscle cells can increase in size (hypertrophy) with regular exercise

3. Frequency of stimulation: the higher the frequency, the greater the force

 Stimuli are added together

4. Degree of muscle stretch: muscle fibers with sarcomeres that are 80–120%

their normal resting length generate more force

 If sarcomere is less than 80% resting length, filaments overlap too much, and

force decreases

 If sarcomere is greater than 120% of resting length, filaments do not overlap

enough so force decreases

Velocity and Duration of Contraction

How fast a muscle contracts and how long it can stay contracted is influenced by:

– Muscle fiber type

– Load

– Recruitment

Muscle fiber type

– Classified according to two characteristics

1. Speed of contraction – slow or fast fibers

according to:

– Speed at which myosin ATPases split ATP

– Pattern of electrical activity of motor neurons

2. Metabolic pathways used for ATP synthesis

– Oxidative fibers: use aerobic pathways

– Glycolytic fibers: use anaerobic glycolysis

Based on these two criteria, skeletal muscle fibers can be classified into three

types:

 Slow oxidative fibers, fast oxidative fibers, or fast glycolytic fibers

– Most muscles contain mixture of fiber types, resulting in a range of contractile

speed and fatigue resistance

 All fibers in one motor unit are the same type

 Genetics dictate individual’s percentage of each

Muscle fiber type (cont.)

Different muscle types are better suited for different jobs

 Slow oxidative fibers: low-intensity, endurance activities

– Example: maintaining posture

 Fast oxidative fibers: medium-intensity activities

– Example: sprinting or walking

 Fast glycolytic fibers: short-term intense or powerful movements

– Example: hitting a baseball

Load and recruitment

– Load: muscles contract fastest when no load is added

 The greater the load, the shorter the duration of contraction

 The greater the load, the slower the contraction

– Recruitment: the more motor units contracting, the faster and more prolonged the

contraction

Aerobic (Endurance) Exercise

such as jogging, swimming, biking leads to increased:

 Muscle capillaries

 Number of mitochondria

 Myoglobin synthesis

– Results in greater endurance, strength, and resistance to fatigue

– May convert fast glycolytic fibers into fast oxidative fibers

Resistance exercise

(typically anaerobic), such as weight lifting or isometric exercises,

leads to

– Muscle hypertrophy

 Due primarily to increase in fiber size

– Increased mitochondria, myofilaments, glycogen stores, and connective tissue

– Increased muscle strength and size

Clinical – Homeostatic Imbalance

Muscles must be active to remain healthy

• Disuse atrophy (degeneration and loss of mass)

– Due to immobilization or loss of neural stimulation

– Can begin almost immediately.

• Muscle strength can decline 5% per day

• Paralyzed muscles may atrophy to one-fourth initial size

• Fibrous connective tissue replaces lost muscle tissue

• Rehabilitation is impossible at this point

Smooth Muscle (1 of 2)

Found in walls of most hollow organs:

– Respiratory, digestive, urinary, reproductive, circulatory (except in smallest of blood

vessels) except heart

– Not found in heart – heart contains cardiac muscle, not smooth

• Most smooth muscle organized into sheets of tightly packed fibers

Most organs contain two layers of sheets with fibers oriented at right angles to each

other.

– Longitudinal layer: fibers run parallel to long axis of organ

 Contraction causes organ to shorten

– Circular layer: fibers run around circumference of organ

 Contraction causes lumen of organ to constrict

• Alternating contractions and relaxations of layers mix and squeeze substances through

lumen of hollow organs

Differences between Smooth and Skeletal

Muscle Fibers

Smooth muscle fibers are spindle-shaped fibers

– thin and short compared with skeletal muscle fibers which are wider and much

longer

– Only one nucleus, no striations

• Lacks connective tissue sheaths

– Contains endomysium only

Contain varicosities (bulbous swellings) of nerve fibers instead of neuromuscular

junctions

– Varicosities store and release neurotransmitters into a wide synaptic cleft referred

to as a diffuse junction

– Innervated by the autonomic nervous system

Smooth muscle has less elaborate SR, and no T tubules

– SR is less developed than in skeletal muscle

 SR does store intracellular Ca2+, but most calcium used for contraction has

extracellular origins

• Sarcolemma contains pouchlike infoldings called caveolae

– Caveolae contain numerous Ca2+ channels that open to allow rapid influx of

extracellular Ca2+

Differences between Smooth and Skeletal

Muscle Fibers (4

Smooth muscle fibers are usually electrically connected via gap junctions whereas

skeletal muscle fibers are electrically isolated

– Gap junctions are specialized cell connections that allow depolarization to spread

from cell to cell

• There are no striations and no sarcomeres, but they do contain overlapping thick and

thin filaments

Smooth muscle also differs from skeletal muscle in following ways:

– Thick filaments are fewer and have myosin heads along entire length

 Ratio of thick to thin filaments (1:13) is much lower than in skeletal muscle

(1:2)

 Thick filaments have heads along entire length, making smooth muscle as

powerful as skeletal muscle

– No troponin complex

 Does contain tropomyosin, but not troponin

 Protein calmodulin binds Ca2+

Thick and thin filaments arranged diagonally

 Myofilaments are spirally arranged, causing smooth muscle to contract in

corkscrew manner

– Intermediate filament–dense body network

 Contain lattice-like arrangement of non contractile intermediate filaments that

resist tension

 Dense bodies: proteins that anchor filaments to sarcolemma at regular

intervals

– Correspond to Z discs of skeletal muscle

 During contraction, areas of sarcolemma between dense bodies bulge outward

– Make muscle cell look puffy

Mechanism of contraction

Slow, synchronized contractions

– Cells electrically coupled by gap junctions

 Action potentials transmitted from fiber to fiber

– Some cells are self-excitatory (depolarize without external stimuli)

 Act as pacemakers for sheets of muscle

 Rate and intensity of contraction may be modified by neural and chemical

stimuli

Contraction in smooth muscle is similar to skeletal muscle contraction in following

ways:

 Actin and myosin interact by sliding filament mechanism

 Final trigger is increased intracellular Ca2+ level

 ATP energizes sliding process

 Contraction stops when Ca2+ is no longer available

Contraction in smooth muscle is different from skeletal muscle in following ways:

 Some Ca2+ still obtained from SR, but mostly comes from extracellular space

 Ca2+ binds to calmodulin, not troponin

 Activated calmodulin then activates myosin kinase (myosin light chain

kinase)

 Activated myosin kinase phosphorylates myosin head, activating it

– Leads to crossbridge formation with actin

Stopping smooth muscle contraction requires more steps than skeletal muscle

 Relaxation requires:

– Ca2+ detachment from calmodulin

– Active transport of Ca2+ into SR and extracellularly

– Dephosphorylation of myosin to inactive myosin

Energy efficiency of smooth muscle contraction

Slower to contract and relax but maintains contraction for prolonged periods with

little energy cost

 Slower ATPases

 Myofilaments may latch together to save energy

– Most smooth muscle maintain moderate degree of contraction constantly without

fatiguing

 Referred to as smooth muscle tone

– Makes ATP via aerobic respiration pathways

Regulation of contraction

– Controlled by nerves, hormones, or local chemical changes

– Neural regulation

Neurotransmitter binding causes either graded (local) potential or action

potential

– Results in increases in Ca2+ concentration in sarcoplasm

– Response depends on neurotransmitter released and type of receptor

molecules

• One neurotransmitter can have a stimulatory effect on smooth

muscle in one organ, but an inhibitory effect in a different organ

Hormones and local chemicals

 Some smooth muscle cells have no nerve supply

– Depolarize spontaneously or in response to chemical stimuli that bind to

G protein–linked receptors

– Chemical factors can include hormones, high CO2, pH, low oxygen

 Some smooth muscles respond to both neural and chemical stimuli

Special features of smooth muscle contraction

Response to stretch

• Stress-relaxation response: responds to stretch only briefly, then adapts to

new length

– Retains ability to contract on demand

– Enables organs such as stomach and bladder to temporarily store

contents

– Length and tension changes

• Can contract when between half and twice its resting length

– Allows organ to have huge volume changes without becoming flabby

when relaxed

Types of Smooth Muscle

Smooth muscle varies in different organs by:

1. Fiber arrangement and organization

2. Innervation

3. Responsiveness to various stimuli

• All smooth muscle is categorized as either:

– Unitary

– Multiunit

Unitary smooth muscle

– Commonly referred to as visceral muscle

– Found in all hollow organs except heart

– Possess all common characteristics of smooth muscle:

 Arranged in opposing (longitudinal and circular) sheets

 Innervated by varicosities

 Often exhibit spontaneous action potentials

 Electrically coupled by gap junctions

 Respond to various chemical stimuli

Multiunit smooth muscle

– Located in large airways in lungs, large arteries, arrector pili muscles, and iris of

eye

– Very few gap junctions, and spontaneous depolarization is rare

– Similar to skeletal muscle in some features

 Consists of independent muscle fibers

 Innervated by autonomic nervous system, forming motor units

 Graded contractions occur in response to neural stimuli that involve

recruitment

– Different from skeletal muscle because, like unitary smooth muscle, it is controlled

by autonomic nervous system and hormones

Developmental Aspects of Muscle (

All muscle tissues develop from embryonic myoblasts

• Multinucleated skeletal muscle cells form by fusion of many myoblasts

• Growth factor stimulates clustering of ACh receptors at neuromuscular junctions

• Cardiac and smooth muscle myoblasts do not fuse, but develop gap junctions

– Cardiac muscle cells start pumping when embryo is 3 weeks old

Regeneration of muscle:

– Myoblast-like skeletal muscle satellite cells have limited regenerative ability

– Cardiomyocytes can divide at modest rate, but injured heart muscle is mostly

replaced by connective tissue

– Smooth muscle regenerates throughout life

• Cardiac and skeletal muscle can lengthen and thicken in growing child

– In adults, leads to hypertrophy

Muscular development in infants reflects neuromuscular coordination

– Development occurs head to toe, and proximal to distal

 A baby can lift its head before it is able to walk

• Peak natural neural control occurs by midadolescence

– Athletics and training can continue to improve neuromuscular control

Developmental Aspects of Muscle (5

Difference in muscle mass between sexes:

– Female skeletal muscle makes up 36% of body mass

– Male skeletal muscle makes up 42% of body mass, primarily as a result of

testosterone

 Males have greater ability to enlarge muscle fibers, also because of

testosterone

– Body strength per unit muscle mass is the same in both sexes

Aging muscles:

– With age, connective tissue increases, and muscle fibers decrease

– By age 30, loss of muscle mass (sarcopenia) begins

– Regular exercise reverses sarcopenia

– Atherosclerosis may block distal arteries, leading to intermittent claudication

(limping) and severe pain in leg muscles