10-1

3 Types of Muscle Tissue1. Skeletal2. Cardiac3. Smooth

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

10-2

• Cardiac muscle– striated in appearance– involuntary control– autorhythmic because of built in pacemaker

10-3

• Smooth muscle– attached to hair follicles in skin– in walls of hollow organs - blood vessels & GI– nonstriated in appearance– involuntary– autorhythmic

10-4

Functions of Muscle Tissue

• Producing body movements

• Stabilizing body positions

• Regulating organ volumes– bands of smooth muscle called sphincters

• Movement of substances within the body– blood, lymph, urine, air, food and fluids, sperm

• Producing heat– involuntary contractions of skeletal muscle (shivering)

10-5

Properties of Muscle Tissue• Excitability - respond to chemicals released from

nerve cells

• Conductivity - ability to propagate electrical signals over membrane

• Contractility - ability to shorten and generate force- 2 types of shortening: isometric and isotonic

• Extensibility - ability to be stretched without being damaged

• Elasticity - ability to return to original shape after being stretched

10-6

Skeletal Muscle - Connective Tissue

• Superficial fascia is loose connective tissue & fat underlying the skin, path for BV & nerves

• Deep fascia = dense irregular connective tissue around muscles with similar functions, isolates muscles from body allowing movement

• Connective tissue components of the muscle include– epimysium = surrounds the whole muscle – perimysium = surrounds bundles (fascicles) of 10-100

muscle cells– endomysium = separates individual muscle cells

• All these connective tissue layers extend beyond the muscle belly to form the tendon

10-7

10-8

Connective Tissue Components

10-9

Nerve and Blood Supply

• Each skeletal muscle is supplied by a nerve, artery and vein, and a rich capillary bed.

• Each motor neuron supplies multiple muscle cells (neuromuscular junction = NMJ)

• Each muscle cell is supplied by one motor neuron terminal branch and is in contact with one or two capillaries.– nerve fibers & capillaries are found in the

endomysium between individual cells

10-10

Fusion of Myoblasts into Muscle Fibers

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

• Mature muscle cells can not divide• Muscle growth is a result of cellular enlargement (hypertrophy) &

not cell division (hyperplasia)• Satellite cells retain the ability to regenerate new muscle fibers.

10-11

Muscle Fiber = Myofiber

• Muscle cells are long, cylindrical & multinucleated • Sarcolemma = muscle cell membrane• Sarcoplasm filled with tiny threads called myofibrils &

myoglobin (red-colored, oxygen-binding protein)

10-12

Transverse Tubules

• T (transverse) tubules are invaginations of the sarcolemma into the center of the cell– filled with extracellular fluid– carry muscle action potentials down into cell

• Mitochondria lie in rows throughout the cell– near the muscle proteins that use ATP during contraction

10-13

Myofibrils & Myofilaments

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

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

10-14

Sarcoplasmic Reticulum (SR)

• System of tubular sacs similar to smooth ER in nonmuscle cells

• Stores Ca+2 in a relaxed muscle• Release of Ca+2 triggers muscle contraction• Forms ‘triad’ with T-tubules

10-15

Atrophy and Hypertrophy

• Atrophy– wasting away of muscles– caused by disuse (disuse atrophy) or severing of the

nerve supply (denervation atrophy)– the transition to connective tissue can not be reversed

• Hypertrophy– increase in the diameter of muscle fibers, not number– resulting from forceful, repetitive muscular activity

and an increase in myofibrils, SR & mitochondria

10-16

Filaments and the Sarcomere• Thick and thin filaments overlap each other in

a pattern that creates striations (light I bands and dark A bands)

• The I band region contains only thin filaments.

• They are arranged in compartments called sarcomeres, separated by Z discs.

• In the overlap region, six thin filaments surround each thick filament

10-17

Overlap of Thick & Thin Myofilaments within a Myofibril

Dark(A) & light(I) bands visible with an electron microscope

10-18

Thick & Thin Myofilaments

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

10-19

Exercise-Induced Muscle Damage• Intense exercise does cause muscle damage

– electron micrographs reveal torn sarcolemmas, damaged myofibrils and disrupted Z discs

– increased blood levels of myoglobin & creatine phosphate found only inside muscle cells

• Delayed onset muscle soreness– 12 to 48 hours after strenuous exercise– stiffness, tenderness and swelling due to

microscopic cell damage

10-20

The Proteins of Muscle

• Myofibrils are built of 3 kinds of protein– contractile proteins

• myosin and actin

– regulatory proteins which turn contraction on & off• troponin and tropomyosin

– structural proteins which provide proper alignment, elasticity and extensibility

• titin, myomesin, nebulin and dystrophin

10-21

The Proteins of Muscle - Myosin

• Thick filaments are composed of myosin – each molecule resembles two golf clubs with twisted together

handles– myosin heads (cross bridges) extend toward the thin filaments

• Held in place by the M line proteins - myomesin.

10-22

The Proteins of Muscle - Actin

• Thin filaments are made of actin, troponin, & tropomyosin • The myosin-binding site on each actin molecule is covered by

tropomyosin in relaxed muscle• The thin filaments are held in place by Z lines. From one Z line to the

next is a sarcomere.

10-23

Structure of Actin and Myosin

10-24

10-25

The Proteins of Muscle - Titin

• Titin anchors thick filament to the M line and extends to the Z disc.• Titan is filamentous, springy; maintains side-by-side orientation of

sliding filaments• The portion of the molecule between the Z disc and the end of the

thick filament can stretch to 4 times its resting length and spring back unharmed.

• Role in recovery of the muscle from being stretched, prevents overextension, maintains the position of A band in the center of the sarcomere.

10-26

Other Structural Proteins

• The M line (myomesin) connects to titin and adjacent thick filaments.

• Nebulin, an inelastic protein helps align the thin filaments.• Dystrophin links thin filaments to integral sarcolemmal

proteins and transmits the tension generated to the tendon.

10-27

Components of Sarcomeres

10-28

Sliding Filament Model

• Actin myofilaments sliding over myosin to shorten sarcomeres– Actin and myosin do not change length– Sarcomere shortening is responsible for skeletal

muscle contraction

• During relaxation, sarcomeres lengthen

10-29

Sliding Filament Mechanism Of Contraction • Myosin cross bridges

pull on thin filaments• Thin filaments slide

inward (toward M line)• Z Discs come toward

each other• Sarcomeres shorten.The

muscle fiber shortens. The muscle shortens

• Notice : Thick & thin filaments do not change in length!!

10-30

Sarcomere Shortening

10-31

Sarcomere shortening

10-32

How Does Contraction Begin?

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

• ACh diffuses to receptors on the sarcolemma & Na+ channels open, Na+ rushes into the cell

• A muscle action potential spreads over sarcolemma and down into the transverse tubules

• SR releases Ca+2 into the sarcoplasm

• Ca+2 binds to troponin & causes troponin-tropomyosin complex to move & reveal myosin binding sites on actin - contraction cycle begins

10-33

Contraction Cycle• Repeating sequence of events that cause the

thick & thin filaments to move past each other.

• 4 steps to contraction cycle– ATP hydrolysis– attachment of myosin to actin to form crossbridges– power stroke– detachment of myosin from actin

• Cycle keeps repeating as long as there is ATP available & high Ca+2 level near thin filament

10-34

ATP and Myosin

• Myosin heads are activated by ATP• Activated heads attach to actin & pull (power stroke)• ADP is released.• Thin filaments slide past the thick filaments• ATP binds to myosin head & detaches it from actin• All of these steps repeat over and over

– if ATP is available &

– Ca+2 level near the troponin-tropomyosin complex is high

10-35

Steps in the Contraction Cycle

10-36

Cross-Bridge Movement

10-37

Breakdown of ATP and Cross Bridge Movement During Muscle Contraction

10-38

Action Potentials and Muscle Contraction

10-39

Action potential along the T tubules opens Ca channels on the SR.T-tubules and SR are physically linked by a membrane protein – RYANODINE RECEPTOR which also functions as a Ca channel. The ryanodine receptor comes in contact with T-tubule membrane proteins – dihydropyridine (DHP) receptors. DHPs function as voltage sensors. Voltage change alters the DHPs conformation which opens the ryanodine receptors

10-40

Action Potentials and Muscle Contraction

10-41

Relaxation• Muscle action potential ceases

• Acetylcholinesterase (AChE) breaks down ACh within the synaptic cleft

• Ca+2 release channels on the SR close

• Active transport pumps Ca2+ back into storage in the sarcoplasmic reticulum

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

• Tropomyosin-troponin complex recovers binding site on the actin

10-42

Neuromuscular Junction (NMJ) or Synapse

• NMJ = myoneural junction– end of axon nears the surface of a muscle fiber at its motor end plate region

(remain separated by synaptic cleft or gap)

10-43

Neuromuscular Junction (NMJ)

• Synapse or NMJ– Presynaptic terminal– Synaptic cleft– Postsynaptic membrane or motor end-plate

• Synaptic vesicles– Acetylcholine: Neurotransmitter– Acetylcholinesterase: A degrading enzyme in synaptic cleft

10-44

Ion Channels

• Types– Ligand-gated

• Example: neurotransmitters

– Voltage-gated• Open and close in

response to small voltage changes across plasma membrane

10-45

Structures of NMJ Region

• Synaptic end bulbs are swellings of axon terminals

• End bulbs contain synaptic vesicles filled with acetylcholine (ACh)

• Motor end plate membrane contains 30 million ACh receptors.

10-46

Function of Neuromuscular Junction

10-47

Function of Neuromuscular Junction

10-48

Events Occurring After a Nerve Signal• Arrival of nerve impulse at nerve terminal causes release of

ACh from synaptic vesicles• ACh binds to receptors on muscle motor end plate opening

the gated ion channels so that Na+ can rush into the muscle cell

• Inside of muscle cell becomes more positive, triggering a muscle action potential that travels over the cell and down the T tubules

• The release of Ca+2 from the SR is triggered and the muscle cell will shorten & generate force

• Acetylcholinesterase breaks down the ACh attached to the receptors on the motor end plate so the muscle action potential will cease and the muscle cell will relax.

10-49

Pharmacology of the NMJ• Botulinum toxin blocks release of neurotransmitter at the

NMJ so muscle contraction can not occur– bacteria found in improperly canned food– death occurs from paralysis of the diaphragm

• Curare (plant poison used for arrows)– causes muscle paralysis by blocking the ACh receptors – used to relax muscle during surgery

• Neostigmine (anti-cholinesterase agent)– blocks removal of ACh from receptors - strengthens weak

muscle contractions (as in myasthenia gravis)– also an antidote for curare after surgery is finished

10-50

Excitation - Contraction Coupling

• All the steps that occur from the muscle action potential reaching the T tubule to contraction of the muscle fiber.

10-51

Overview: From Start to Finish

• Nerve ending• Neurotransmittor• Muscle membrane• Stored Ca+2

• ATP• Muscle proteins

10-52

Rigor Mortis• Rigor mortis is a state of muscular rigidity that

begins 3-4 hours after death and lasts about 24 hours

• After death, Ca+2 ions leak out of the SR and allow myosin heads to bind to actin

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

10-53

• Optimal overlap of thick & thin filaments– produces greatest number of crossbridges and the

greatest amount of tension

• Overstretching muscle (past optimal length)– fewer cross bridges exist & less force is produced

• If muscle is overly shortened (less than optimal)– fewer cross bridges exist & less force is produced– thick filaments crumpled by Z discs

• Normally– resting muscle length remains between 70 to 130% of

the optimum

Length of Muscle Fibers

10-54

10-55

Length Tension Curve

• Graph of Force of contraction(Tension) versus Length of sarcomere

• Optimal overlap at the topof the graph

• When the cell is too stretched

little force is produced• When the cell is too short, again

little force is produced

10-56

Muscle MetabolismProduction of ATP in Muscle Fibers

• Muscle uses ATP at a great rate when active

• Sarcoplasmic ATP only lasts for few seconds

• 3 sources of ATP production within muscle– creatine phosphate– anaerobic cellular respiration– aerobic cellular respiration

10-57

Energy Sources

• ATP provides immediate energy for muscle contractions from 3 sources– Creatine phosphate

• During resting conditions stores energy to synthesize ATP

– Anaerobic respiration• Occurs in absence of oxygen and results in breakdown of

glucose to yield ATP and lactic acid

– Aerobic respiration• Requires oxygen and breaks down glucose to produce ATP,

carbon dioxide and water

• More efficient than anaerobic

10-58

Creatine Phosphate• Excess ATP within resting muscle used to form creatine

phosphate• Creatine phosphate is 3-6

times more plentiful than ATP within muscle

• Its quick breakdownprovides energy for creation of ATP

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

• Athletes tried creatine supplementation – gain muscle mass but shut down bodies own synthesis (safety?)

10-59

Anaerobic Cellular Respiration

• ATP produced from glucose breakdown into pyruvic acid during glycolysis – if no O2 present

• pyruvic converted to lactic acid which diffuses into the blood

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

10-60

Aerobic Cellular Respiration

• ATP for any activity lasting over 30 seconds – if sufficient oxygen is available, pyruvic acid enters the

mitochondria to generate ATP, water and heat

– fatty acids and amino acids can also be used by the mitochondria

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

10-61

Fatigue

• Decreased capacity to work and reduced efficiency of performance

• Types:• Psychological

– Depends on emotional state of individual

• Muscular– Results from ATP depletion

• Synaptic– Occurs in NMJ due to lack of acetylcholine

10-62

Muscle Fatigue

• Inability to contract after prolonged activity– central fatigue is feeling of tiredness and a

desire to stop (protective mechanism)– depletion of creatine phosphate– decline of Ca+2 within the sarcoplasm

• Factors that contribute to muscle fatigue– insufficient oxygen or glycogen– buildup of lactic acid and ADP, decrease in pH– insufficient release of acetylcholine from motor

neurons, lack of Ca+2

10-63

Oxygen Consumption after ExerciseOxygen Debt

• Muscle tissue has two sources of oxygen.– diffuses in from the blood– released by myoglobin inside muscle fibers

• Aerobic system requires O2 to produce ATP needed for prolonged activity– increased breathing effort during exercise

• Recovery oxygen uptake– elevated oxygen use after exercise (oxygen debt)– lactic acid is converted back to pyruvic acid– elevated body temperature increases rate of all

metabolic reactions

10-64

The Motor Unit

• Motor unit = one somatic motor neuron & all the skeletal muscle cells (fibers) it stimulates – muscle fibers normally scattered throughout belly of muscle

– One nerve cell supplies on average 150 muscle cells that all contract in unison.

• Total strength of a contraction depends on how many motor units are activated & how large the motor units are

10-65

Stimulus Strength and Muscle Contraction

• All-or-none law for muscle fibers– Contraction of equal force in

response to each action potential

• Sub-threshold stimulus

• Threshold stimulus

• Stronger than threshold

• Graded response for whole muscles– Strength of contractions range

from weak to strong depending on stimulus strength (frequency of action potentials)

10-66

Twitch Contraction

• Brief contraction of all fibers in a motor unit in response to – single action potential in its motor neuron

– electrical stimulation of the neuron or muscle fibers

• Myogram = graph of a twitch contraction– the action potential lasts 1-2 msec

– the twitch contraction lasts from 20 to 200 msec

10-67

Parts of a Twitch Contraction• Latent Period – 2 msec

– Ca+2 is being released from SR

– slack is being removed from elastic components

• Contraction Period– 10 to 100 msec

– filaments slide past each other

• Relaxation Period– 10 to 100 msec

– active transport of Ca+2 into SR

• Refractory Period (very short)– muscle can not respond and has lost its excitability

– 5 msec for skeletal & 300 msec for cardiac muscle

10-68

10-69

Wave Summation‘Temporal Summation’

• If second stimulation is applied after the refractory period but before complete muscle relaxation - second contraction is stronger than first (Why?)

10-70

Complete and Incomplete Tetanus

• Unfused tetanus– if stimulate at 20-30 times/second, there will be only partial

relaxation between stimuli

• Fused tetanus– if stimulate at 80-100 times/second, a sustained contraction

with no relaxation between stimuli will result

10-71

Explanation of Summation & Tetanus

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

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

10-72

Motor Unit Recruitment‘Spatial Summation’

• Motor units in a whole muscle fire asynchronously– some fibers are active others are relaxed – delays muscle fatigue so contraction can be sustained

• Produces smooth muscular contraction– not series of jerky movements

• Precise movements require smaller contractions– motor units must be smaller (fewer fibers/nerve)

• Large motor units are active when greater tension is needed

10-73

Multiple Motor Unit Summation

• A whole muscle contracts with a small or large force depending on number of motor units stimulated to contract

10-74

Treppe• Graded response• Occurs in whole

muscle rested for prolonged period

• Each subsequent contraction is stronger than previous until all equal after few stimuli

• Reasons?

Note that although each individual muscle fiber and each motor unit respond in all-or-none fashion, the muscle as a whole responds in graded fashion.

10-75

Types of Muscle Contractions

• Isometric (static): No change in length while tension may change– Postural muscles of body

• Isotonic (dynamic): Change in length with constant tension– Concentric: Overcomes opposing resistance and muscle

shortens– Eccentric: Tension maintained but muscle lengthens– Isokinetic: Maximal tension during contraction at

constant speed over full range of motion

• Muscle tone: Constant tension by muscles for long periods of time

10-76

Isotonic and Isometric Contraction

• Isotonic contractions = a load is moved – concentric contraction = a muscle shortens to produce force and

movement– eccentric contractions = a muscle lengthens while maintaining

force (most likely to cause injury!)

• Isometric contraction = no movement occurs– tension is generated without muscle shortening– maintaining posture & supporting objects in a fixed position

10-77

Inju

red

fib

ers

(%

tota

l)

0

5

10

15

20control *passiveisometriclengthening

* different from zero (p<0.05)

Only lengthening contractions result in damaged fibers

Other Measures of Contraction-Induced Injury

enzyme release from degenerating muscle fibers

in human beings, subjective reports of muscle soreness

in the absence of fatigue, a decrease in the development of force

immediate mechanical disruption observed by EM.

Koh & Brooks (2001) Am J Physiol 281:R155-R161.

10-78

Muscle Tone

• Involuntary contraction of a small number of motor units (alternately active and inactive in a constantly shifting pattern)– keeps muscles firm even though relaxed– does not produce movement

• Essential for maintaining posture (head upright)• Important in maintaining blood pressure

– tone of smooth muscles in walls of blood vessels

10-79

Size Principleof motor unit recruitment

The smallest motor units are always recruited first, and recruitment proceeds with successively larger motor units as more force is needed by the muscle.Smallest motor units are recruited first because they have the smallest neuronal somas (cell bodies), which require less stimulation to fire action potentials. In addition, small motor units have smaller muscle fibers, which generate the least amount of force.

10-80

• Active versus passive tension

Passive = the tension in the muscle present before contraction;

Active = the tension developed due to the contraction

• Velocity of muscle shortening decreases with increased load – at maximal load, the velocity is zero = isometric contraction

• Sarcomeres are organized in ‘series’ and in ‘parallel’. At the level of sarcomere organization, how would you increase the tension? Amount of shortening?

10-81

Figure 6-9 Relation of muscle length to tension in the muscle both before and during muscle contraction.

Downloaded from: StudentConsult (on 10 February 2006 03:56 PM)

© 2005 Elsevier

10-82

Figure 6-10 Relation of load to velocity of contraction in a skeletal muscle with a cross section of 1 square

centimeter and a length of 8 centimeters.Downloaded from: StudentConsult (on 10 February 2006 03:56 PM)

© 2005 Elsevier

10-83

Peak power obtained at intermediate loads and intermediate velocities.

Power output: the most physiologically relevant marker of performance

Power = work / time= force x distance / time= force x velocity

Figure from Berne and Levy, PhysiologyMosby—Year Book, Inc., 1993.

10-84

Variations in Skeletal Muscle Fibers• Myoglobin, mitochondria and capillaries

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

– white muscle fibers• less myoglobin and fewer capillaries give fibers their pale

color

• Contraction and relaxation speeds vary– how fast myosin ATPase hydrolyzes ATP

• Resistance to fatigue– different metabolic reactions used to generate ATP

10-85

Slow and Fast Fibers• Slow-twitch

– Contract more slowly, smaller in diameter, better blood supply, more mitochondria, more fatigue-resistant than fast-twitch

• Fast-twitch– Respond rapidly to nervous stimulation, contain myosin

to break down ATP more rapidly, less blood supply, fewer and smaller mitochondria than slow-twitch

• Distribution– Most muscles have both, but proportion varies for each

muscle• Effects of exercise

– Hypertrophies: Increases in muscle size– Atrophies: Decreases in muscle size

10-86

Classification of Muscle Fibers

• Type I, slow oxidative (slow-twitch)

– red in color (lots of mitochondria, myoglobin & blood vessels)

– prolonged, sustained contractions for maintaining posture

• Type IIb, fast oxidative-glycolytic (fast-twitch)

– “pink” in color (lots of mitochondria, myoglobin & blood vessels)

– split ATP at very fast rate; used for walking and sprinting

• Type IIa, fast glycolytic (fast-twitch)

– white in color (few mitochondria & BV, low myoglobin)

– anaerobic movements for short duration; used for weight-lifting

10-87

Shortening velocity dependent on ATPase activity

Different myosin heavy chains (MHCs) have different ATPase activities.

There are at least 7 separate skeletal muscle MHC genes…arranged in series on chromosome 17.

Two cardiac MHC genes located in tandem on chromosome 14.

The slow cardiac MHC is the predominant gene expressed in slow fibersof mammals.

Goldspink (1999) J Anat 194:323-334.

10-88

Physiological profiles of motor units:all fibers in a motor unitare of the same fiber typeSlow motor units contain slow fibers: • Myosin with long cycle time and therefore uses ATP at a slow rate.• Many mitochondria, so large capacity to replenish ATP.• Economical maintenance of force during isometric contractions and efficient performance of repetitive slow isotonic contractions.

Fast motor units contain fast fibers: • Myosin with rapid cycling rates. • For higher power or when isometric force produced by slow motor units is insufficient. • Type FOG fibers are fast and adapted for producing sustained power. • Type FG fibers are faster, but non-oxidative and fatigue rapidly. Modified from Burke and Tsairis, Ann NY Acad Sci 228:145-159, 1974.

FG

FOG

SO

10-89

type I IIb IIaSO FOG FG

Color red pink whiteSpeed of contraction slow fast fastMax force generated low intermed highFiber diameter small intermed largeMotor unit size small intermed largeResistance to fatigue high intermed lowCapillaries many many fewMb content high high lowMitochondria many many fewGlycogen low intermed highMyosin-ATPase low high highOxidative phosphoryl’n high high lowAnaerobic glycolysis low intermed highSensitivity to hypoxia high intermed low

10-90

Fiber Types within a Whole Muscle• Most muscles contain a mixture of all three fiber

types• Proportions vary with the usual action of the

muscle– neck, back and leg muscles have a higher proportion

of postural, slow oxidative fibers– shoulder and arm muscles have a higher proportion

of fast glycolytic fibers

• All fibers of any one motor unit are same.• Different types of fibers are recruited as needed.

10-91

Endurance training

Little hypertrophy but major biochemical adaptations within muscle fibers.

Increased numbers of mitochondria; concentration and activities of oxidative enzymes (e.g. succinate dehydrogenase, see below).

Control 12-weekstreadmill running

Succinate dehy-drogenase (SDH)activity: Low activity lightHigh activity dark

Images courtesy of John Faulkner and Timothy White

10-92

Strength training

Early gains in strength appear to be predominantly due to neural factors…optimizing recruitment patterns.

Long term gains almost solely the result of hypertrophy i.e. increased size.

(Compare the changes in strength vs endurance training.)

10-93

Control Prolongedbed rest

Disuse causes atrophy - USE IT OR LOSE IT!

Individual fiber atrophy (loss of myofibrils) with no loss in fibers.

Effect more pronounced in Type II (fast) fibers.

“Completely reversible” (in young healthy individuals).

ATPase activity:

Type I (slow) fibers - light

Type II (fast) fibers – dark(staining is reversed)

Images courtesy of John Faulkner

Fast- (II)Slow- (I)

10-94

Anabolic Steroids• Similar to testosterone• Increases muscle size, strength, and endurance• Many very serious side effects

– liver cancer– kidney damage– heart disease– mood swings “-roid rage”– facial hair & voice deepening in females– atrophy of testicles & baldness in males

10-95

Regulation of Contraction• Regulation of contraction due to

– nerve signals from somatic and autonomic nervous system

– changes in local conditions (pH, O2, CO2, temperature & ionic concentrations)

– hormones (epinephrine - relaxes muscle in airways & some blood vessels)

• Stress-relaxation response– when stretched, initially contracts & then tension

decreases to what is needed– stretch hollow organs as they fill & yet pressure

remains fairly constant– when emptied, muscle rebounds & walls firm up

10-96

Regeneration of Muscle• Skeletal muscle fibers cannot divide after 1st year

– growth is enlargement of existing cells– repair

• satellite cells & bone marrow produce some new cells• if not enough numbers - fibrosis occurs (most often)

• Cardiac muscle fibers cannot divide or regenerate– all healing is done by fibrosis (scar formation)

• Smooth muscle fibers (regeneration is possible)– cells can grow in size (hypertrophy)– some cells (uterus) can divide (hyperplasia)– new fibers can form from stem cells in BV walls

10-97

Effects of Aging on Skeletal Muscle

• Reduced muscle mass

• Increased time for muscle to contract in response to nervous stimuli

• Reduced stamina

• Increased recovery time

• Loss of muscle fibers

• Decreased density of capillaries in muscle

10-98

Aging and Muscle Tissue

• Skeletal muscle starts to be replaced by fat beginning at 30 – “use it or lose it”

• Slowing of reflexes & decrease in maximal strength

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

10-99

Performance Declines with Aging - despite maintenance of physical activity Performance Declines with Aging - despite maintenance of physical activity

Age (years)

10 20 30 40 50 60

Pe

rfo

rman

ce (

% o

f pe

ak)

0

20

40

60

80

100

Shotput/DiscusMarathonBasketball (rebounds/game)

D.H. Moore (1975) Nature 253:264-265.

NBA Register, 1992-1993 Edition

10-100

Number of motor units declines during aging- extensor digitorum brevis muscle of human beings

Campbell et al., (1973) J Neurol Neurosurg Psych 36:74-182.

AGE-ASSOCIATED ATROPHY DUE TO BOTH…

Individual fiber atrophy (which may be at least partially preventable and reversible through exercise).

Loss of fibers (which as yet appears irreversible).

10-101

Motorneuronloss

Centralnervoussystem

Motor unit remodeling with agingMotor unit remodeling with aging

Muscle

• Fewer motor units• More fibers/motor unit

AG

ING

10-102

• Muscles in old animals are more susceptible to contraction- induced injury than those in young or adult animals.

Muscle injury may play a role in the development of atrophy with aging.

• Muscles in old animals show delayed and impaired recovery following contraction-induced injury.

• Following severe injury, muscles in old animals display prolonged, possibly irreversible, structural and functional deficits.

10-103

Degeneration-regeneration not necessary to provide musclesprotection from contraction-induced injury

• Despite the increase in susceptibility to injury with aging, and the decreased ability to recover, muscles in old animals (humans?) can be conditioned for protection from injury.

• Maintenance of conditioned fibers, particularly in muscles of elderly people, may prevent inadvertent damage during contractions.

Koh & Brooks (2001) Am J Physiol 281:R155-R161. Force deficit Injured fibers

For

ce d

efic

it (%

con

trol

)

0

10

20

30

40

50

60 Injured fibers (% total)

0

10

20

30

40

50

60non-trained trained passive trained isometric

* *

*

* different from non- -trained (p<0.05)

10-104

Myasthenia Gravis• Progressive autoimmune disorder that blocks the

ACh receptors at the neuromuscular junction • The more receptors are damaged the weaker the

muscle. • More common in women 20 to 40 with possible link

to thymus gland tumors• Begins with double vision & swallowing difficulties

& progresses to paralysis of respiratory muscles • Treatment includes steroids that reduce antibodies

that bind to ACh receptors and inhibitors of acetylcholinesterase

10-105

Muscular Dystrophies • Inherited, muscle-destroying diseases • Sarcolemma tears during muscle contraction• Mutated gene is on X chromosome so problem is with

males almost exclusively• Appears by age 5 in males and by 12 may be unable to walk• Degeneration of individual muscle fibers produces atrophy

of the skeletal muscle• Gene therapy is hoped for with the most common form =

Duchenne muscular dystrophy

10-106

• Proteins localized in the nucleus, cytosol, cytoskeleton, sarcolemma, and ECM.

Cohn and Campbell (2000) Muscle Nerve 23:1459-1471.

• Since the discovery of dystrophin, numerous genetic disease loci have been linked to protein products and to cellular phenotypes, generating models for studying the pathogenesis of the dystrophies.

Muscular Dystrophy:A frequently fatal disease of muscle deterioration• Muscular dystrophies have in the past been classified based on subjective and sometimes subtle differences in clinical presentation, such as age of onset, involvement of particular muscles, rate of progression of pathology, mode of inheritance.

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(Some components of the dystrophin glycoproteincomplex are relativelyrecent discoveries, so onecannot assume that all players are yet known.)

DGC (dystroglycan

complex)

dystrophindystroglycan ( and )sarcoglycans (, , , )syntrophins (, 1)dystrobrevins (, )sarcospanlaminin-2 (merosin)

Cohn and Campbell (2000) Muscle Nerve 23:1459-1471.

Dystrophin function: transmission of force to extracellular matrix

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Abnormal Contractions• Spasm = involuntary contraction of single

muscle

• Cramp = a painful spasm

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

• Tremor = rhythmic, involuntary contraction of opposing muscle groups

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

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Muscle Attachment Sites:Origin and Insertion

• Skeletal muscles shorten & pull on the bones they are attached to• Origin is the bone that does not move when muscle shortens

(normally proximal)• Insertion is the movable bone (some 2 joint muscles)• Fleshy portion of the muscle in between attachment sites = belly

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Lever Systems and Leverage• Muscle acts on rigid rods (bone)

that move around a fixed point called a fulcrum

• Resistance is weight of bodypart & perhaps an object

• Effort or load is work doneby muscle contraction

• Mechanical advantage– the muscle whose attachment is farther from the joint will

produce the most force

– the muscle attaching closer to the joint has the greater range of motion and the faster the speed it can produce

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First - Class LeverFulcrum is between force and resistance

• May or may not produce mechanical advantage depending on location of effort & resistance– if effort is further from fulcrum than

resistance, then a strong resistance can be moved

– (+) Need small tension to balance weight

– (-) Limitations are how far a load can be moved and how heavy a load can be

• Head resting on vertebral column– weight of face is the resistance– joint between skull & atlas is fulcrum– posterior neck muscles provide effort

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Second - Class LeverResistance is between fulcrum and effort

• Similar to a wheelbarrow• (+) Always produce mechanical

advantage (muscle tension needed is less than the resistance)– Resistance is always closer to

fulcrum than the effort• (-) Sacrifice speed for force• (-) Sacrifice distance a load can be

moved (it is less than the distance a muscle shortens)

• Raising up on your toes– resistance is body weight– fulcrum is ball of foot– effort is contraction of calf

muscles which pull heel up off of floor

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Third - Class LeverForce is between fulcrum and resistance

• Most common levers in the body• (-) Always produce a mechanical

disadvantage(muscle tension needed is greater than the resistance)– effort is always closer to fulcrum

than resistance• (+) Favors speed and range of

motion over force• Flexor muscles at the elbow

– resistance is weight in hand– fulcrum is elbow joint– effort is contraction of biceps

brachii muscle

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Coordination Within Muscle Groups

• Most movement is the result of several muscle working at the same time

• Most muscles are arranged in opposing pairs at joints– prime mover or agonist contracts to cause the desired

action

– antagonist stretches and yields to prime mover

– synergists contract to stabilize nearby joints

– fixators stabilize the origin of the prime mover• scapula held steady so deltoid can raise arm