Chapter 9Muscles and Muscle Tissue

J.F. Thompson, Ph.D. & J.R. Schiller, Ph.D. & G. Pitts, Ph.D.

Some Muscle TerminologyMyology: the scientific study of muscle

muscle fibers = muscle cells

myo, mys & sarco: word roots referring to muscle

Three Types of MuscleSkeletal, cardiac, and smooth muscle differ in:

Microscopic anatomy

Location

Regulation by the endocrine system and the nervous system

Characteristics of Skeletal Muscle• Attached primarily to

bones

• Voluntary (conscious) control (usually)

• Contracts quickly, tires easily (fatigable)

• Allows for wide range of forces to be generated

Skeletal Muscle Cells • Long, cylindrical cells

• Striated (banded)

• Multinucleate

Characteristics of Cardiac Muscle• Forms most of heart wall

(myocardium)

• Involuntary (unconscious)

• Autorhythmicity (contracts without external stimuli)

• Fast contraction, non-fatigable

• Beats at constant rhythm that can be modified by neural and hormonal signals

Cardiac Muscle Cells • Branched cells

• Uninucleate (may occasionally be binucleate)

• Striated

• Intercalated discs

Characteristics of Smooth Muscle• Found in the walls of hollow

internal structures (digestive, respiratory, reproductive tracts, blood vessels)

• Arrector pili, pupil of the eye, etc.

• Involuntary (unconscious)

• Long, slow contractions, non-fatigable

Smooth Muscle Cells • Nonstriated =

smooth

• Uninucleate

Functions of Muscle Tissue • Motion: external (walking, running, talking, looking)

and internal (heartbeat, blood pressure, digestion, elimination) body part movements

• Posture: maintain body posture

• Stabilization: stabilize joints – muscles have tone even at rest

• Thermogenesis: generating heat by normal contractions and by shivering

Functional Characteristics• Excitability (irritability)

– the ability to receive and respond to a stimulus (chemical signal molecules)

• Contractility – ability of muscle tissue to shorten

• Extensibility– the ability to be stretched without damage– most muscles are arranged in functionally opposing pairs – as

one contracts, the other relaxes, which permits the relaxing muscle to be stretched back

• Elasticity – the ability to return to its original shape

• Conductivity (impulse transmission)– the ability to conduct excitation over length of muscle

Connective Tissue Wrappings of Skeletal Muscle Tissue

• Superficial Fascia: "hypodermis"

• Deep Fascia: lines body walls & extremities; binds muscle together, separating them into functional groups

• Epimysium: wraps an entire muscle

• Perimysium: subdivides each muscle into fascicles, bundles of 10-100 muscle fibers

• Endomysium: wraps individual muscle fibers

Nerve and Blood Supply • Each muscle fiber is supplied by a branch

of a motor nerve

• Each muscle is supplied by its own arteries and veins

• Blood vessels branch profusely to provide each muscle fiber with a direct blood supply

Attachments (to bone)• Origin: the part of a muscle attached to the stationary

bone (relative to a particular motion)

• Insertion: the part of a muscle attached to the bone that moves (relative to a particular motion)

• Attachments are extensions of connective tissue sheaths beyond a muscle, attaching it to other structures

• Direct attachment: epimysium fused to periosteum

Attachment Structure

• Indirect attachment: connective tissue wrappings gathered into a tendon or aponeurosis which attaches to an origin or insertion on bone

– Tendon: cord (of dense regular connective tissue)

– Aponeurosis: sheet (of dense regular connective tissue)

Microscopic Anatomy of A Skeletal Muscle Fiber

• Muscle fibers (cells): long, cylindrical, and multinucleate (individual muscle cells fuse during embryonic development)

• Sarcolemma: the cell membrane of a muscle fiber

• Sarcoplasm: the cytoplasm of a muscle fiber, rich in oxygen-storing myoglobin protein

Myofibrils of A Skeletal Muscle Fiber

• Myofibrils: bundles of contractile protein filaments (myofilaments) arranged in parallel, fill most of the cytoplasm of each muscle fiber; 100’s to 1000’s per cell

• Sarcomeres: the repeating unit of contraction in each myofibril

Organelles of A Skeletal Muscle Fiber • Mitochondria: provide the

ATP required for contraction

• Sarcoplasmic reticulum (smooth ER): stores Ca2+ ions which serve as second messengers for contraction

Striations/Sarcomeres • Z discs (lines): the boundary

between sarcomeres; proteins anchor the thin filaments; bisects each I band

• A (anisotropic) band: overlap of thick (myosin) filaments & thin filaments

• I (isotropic) band: thin (actin) filaments only

• H zone: thick filaments only

• M line: proteins anchor the adjacent thick filaments

Myofilaments

• Thin filaments: actin (plus some tropomyosin & troponin)

• Thick filaments: myosin

• Elastic filaments: titin (connectin) attaches myosin to the Z discs (very high mol. wt.)

Sarcomeres

• Components of the muscle fiber with myofilaments arranged into contractile units

• The functional unit of striated muscle contraction• Produce the visible banding pattern (striations)

• The myofilaments between two successive z discs

Summary of Muscle Structure

Myosin Protein• Rod-like tail with two heads

• Each head contains ATPase and an actin-binding site; point to the Z line

• Tails point to the M line

• Splitting ATP releases energy which causes the head to “ratchet” and pull on actin fibers

Thick (Myosin) Myofilaments• Each thick filament contains many myosin

units woven together

Thin (Actin) MyofilamentsTwo G actin strands are arranged into helical strands• Each G actin has a binding site for myosin• Two tropomyosin filaments spiral around the actin

strands• Troponin regulatory proteins (“switch molecules”) may

bind to actin and tropomyosin & have Ca2+ binding sites

Muscle Fiber Triads• Triads: 2 terminal cisternae + 1 T tubule • Sarcoplasmic reticulum (SER): modified smooth ER, stores

Ca2+ ions• Terminal cisternae: large flattened sacs of the SER • Transverse (T) tubules: inward folding of the sarcolemma

Regulation of Contraction & The Neuromuscular Junction

The Neuromuscular Junction:

• Where motor neurons communicate with the muscle fibers

• Composed of an axon terminal & motor end plate

– Axon terminal: end of the motor neuron’s branches (axon)

– Motor end plate: the specialized region of the muscle cell plasma membrane adjacent to the axon terminal

The Neuromuscular Junction: • Synapse: point of

communication is a small gap  

• Synaptic cleft: the space between axon terminal & motor end plate  

• Synaptic vesicles: membrane-enclosed sacs in the axon terminals containing the neurotransmitter

The Neuromuscular Junction:

• Neurotransmitter: the chemical that travels across the synapse, i.e., acetylcholine, ACh)  

• Acetylcholine (ACh) receptors: integral membrane proteins which bind ACh  

axonal terminal

motor end plate

Generation of an Action Potential (Excitation)

• Binding of neurotransmitter (ACh) causes the ligand-gated Na+ channels to open

• Opening of the Na+ channels depolarizes the sarcolemma (cell membrane)

Generation of an Action Potential• Initial depolarization

causes adjacent voltage-gated Na+ channels to open; Na+ ions flow in, beginning an action potential

• Action potential: a large transient depolarization of the membrane potential– transmitted over the

entire sarcolemma (and down the T tubules)

Generation of an Action Potential• Repolarization: the return to polarization due to the

closing voltage-gated Na+ channels and the opening of voltage gated K+ channels  

• Refractory period: the time during membrane repolarization when the muscle fiber cannot respond to a new stimulus (a few milliseconds)

  • All-or-none response: once an action potential is

initiated it results in a complete contraction of the muscle cell  

Excitation-Contraction Coupling   • The action potential

(excitation) travels over the sarcolemma, including T-tubules

• DHP receptors serve as voltage sensors on the T-tubules and cause ryanodine receptors on the SR to open and release Ca2+ ions

• And now, for the interactions between calcium and the sarcomere…

The Sliding Filament Model of Muscle Contraction

• Thin and thick filaments slide past each other to shorten each sarcomere and, thus, each myofibril

• The cumulative effect is to shorten the muscle

http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Muscle/Muscle.htm#SKELETAL

• This simulation of the sliding filament model can also be viewed on line at the web site below along with additional information on muscle tissue

Calcium (Ca2+)The “on-off switch”: allows myosin to bind to actin

off on

Calcium Movements Inside Muscle Fibers

Action potential causes release of Ca2+ ions (from the cisternae of the SR)

Ca2+ combines with troponin, causing a change in the position of tropomyosin, allowing actin to bind to myosin and be pulled (“slide”)

Ca2+ pumps on the SR remove calcium ions from the sarcoplasm when the stimulus ends

The Power Stroke & ATP

1. Cross bridge attachment. myosin binds to actin

2. The working stroke. myosin changes shape (pulls actin toward it); releases ADP + Pi

3. Cross bridge detachment. myosin binds to new ATP; releases actin

The Power Stroke & ATP 4. "Cocking" of the

myosin head. ATP hydrolyzed (split) to ADP + Pi; provides potential energy for the next stroke

The “Ratchet Effect” Repeat steps 1-4:

The “ratchet action” repeats the process, shortening the sarcomeres and myofibrils, until Ca2+ ions are removed from the sarcoplasm or the ATP supply is exhausted

AttachPowerStroke

ReleaseRepeat

RATCHET EFFECT ANIMATION

http://www.sci.sdsu.edu/movies/actin_myosin_gif.html

Excitation-Contraction Coupling   1. The action potential

(excitation) travels over the sarcolemma, including T-tubules

2. DHP receptors serve as voltage sensors on the T-tubules and cause ryanodine receptors on the SR to open and release Ca2+ ions

3. Ca2+ binds to troponin, causing tropomyosin to move out of its blocking position

4. Myosin forms cross bridges to actin, the power stroke occurs, filaments slide, muscle shortens

5. Calsequestrin and calmodulin help regulate Ca2+ levels inside muscle cells

Destruction of Acetylcholine   • Acetylcholinesterase: an enzyme that rapidly breaks

down acetylcholine is located in the neuromuscular junction 

– Prevents continuous excitation (generation of more action potentials)  

• Many drugs and diseases interfere with events in the neuromuscular junction  

– Myasthenia gravis: loss of function at ACh receptors (autoimmune disease?)  

– Curare (poison arrow toxin): binds irreversibly to and blocks the ACh receptors

MUSCLE CONTRACTION• One power stroke shortens a muscle about 1%

• Normal muscle contraction shortens a muscle by about 35% – Cross bridge (ratchet effect) cycle repeats

• continue repeating power strokes, continue pulling • increasing overlap of fibers; Z lines come together

– About half the myosin molecules are attached at any time

• Cross bridges are maintained until Ca2+ levels decrease – Ca2+ released in response to action potential delivered by

motor neuron – Ca2+ ATPase pumps Ca2+ ions back into the SR

RIGOR MORTIS IN DEATH • Ca2+ ions leak from SR causing binding of actin and

myosin and some contraction of the muscles

• Lasts ~24 hours, then enzymatic tissue disintegration eliminates it in another 12 hours

Skeletal Muscle Motor Units• The Motor Unit = Motor Neuron + Muscle Fibers to

which it connects (Synapses)  

Skeletal Muscle Motor Units• The size of Motor Units

varies:– Small - two muscle

fibers/unit (larynx, eyes) – Large – hundreds to

thousands/unit (biceps, gastrocnemius, lower back muscles)

• The individual muscle cells/fibers of each unit are spread throughout the muscle for smooth efficient operation of the muscle as a whole

The Myogram

• Myogram: a recording of muscle contraction

• Stimulus: nerve impulse or

electrical charge

• Twitch: a single contraction of all the muscle fibers in a motor unit (one nerve signal)        

Myogram1. Latent period: delay between

stimulus and response  

2. Contraction phase: tension or shortening occurs  

3. Relaxation phase: relaxation or lengthening  

Muscle Twitches

All or none rule: All the muscle fibers of a motor unit contract all the way when stimulated

Graded Muscle Responses• Force of muscle contraction varies

depending on need. How much tension is needed?

• Twitch does not provide much force

• Contraction force can be altered in 3 ways:

1. changing the frequency of stimulation (temporal summation)

2. changing the stimulus strength (recruitment)3. changing the muscle’s length

Temporal Summation • Temporal (wave) summation: contractions repeated before

complete relaxation, leads to progressively stronger contractions

– unfused (incomplete) tetanus: frequency of stimulation allows only incomplete relaxation  

– fused (complete) tetanus: frequency of stimulation allows no relaxation

Treppe: the staircase effect

“warming up” of a muscle fiber

Multiple Motor Unit Summation ( Recruitment)

The stimulation of more motor units leads to more forceful muscle contraction  

The Size Principle

As stimulus intensity increases, motor units leads with larger fibers are recruited  

Stretch: Length-Tension Relationship• Stretch (sarcomere length)

determines the number of cross bridges– extensive overlap of actin

with myosin: less tension– optimal overlap of actin with

myosin: most tension– reduced overlap of actin with

myosin: less tension• Optimal overlap: most cross

bridges available for the power stroke and least structural interference

more resistance

most cross bridges/least resistance

fewest cross bridges

Stretch: Length-Tension RelationshipOptimal length - Lo

• maximum number of cross bridges• no overlap of actin fibers from opposite ends of the sarcomere • normal working muscle range from 70 - 130% of Lo

Contraction of a Skeletal Muscle• Isometric Contraction: Muscle does not shorten• Tension increases

Contraction of a Skeletal Muscle• Isotonic Contraction: tension does not change• Muscle (length) shortens

Regular small contractions caused by spinal reflexes

Respond to tendon stretch receptor sensory inputActivate different motor units over time

Provide constant tension development muscles are firmbut no movement

e.g., neck, back and leg muscles maintain posture

Muscle Tone

Muscle Metabolism• Energy availability

– Not much ATP is available at any given moment– ATP is needed for cross bridges and Ca2+ removal– Maintaining ATP levels is vital for continued activity– Three ways to replenish ATP:

1. Creatine Phosphate energy storage system2. Anaerobic Glycolysis -- Lactic Acid system3. Aerobic Respiration

• CrP stored in cell

• Allows for rapid ATP replenishment

• Only a small amount available (10-30 seconds worth)

Direct Phosphorylation – Creatine Phosphate System

Anaerobic Glycolysis – Lactic Acid System

• Anaerobic system - no O2 required

• Very inefficient, does not create much ATP

• Only useful in short term situations (30 sec - 1 min)

• Produces lactic acid as a by-product

Aerobic System- Uses oxygen for ATP

production

- Oxygen comes from the RBCs in the blood and the myoglobin storage depot

- Uses many substrates: carbohydrates, lipids, proteins

- Good for long term exercise

- May provide 90-100% of the needed ATP during these periods

Summary of Muscle Metabolism

Oxygen Debt• The amount of oxygen needed to

restore muscle tissue (and the body) to the pre-exercise state

• Muscle O2, ATP, creatine phosphate, and glycogen levels, and a normal pH must be restored after any vigorous exercise

• Circulating lactic acid is converted/recycled back to glucose by the liver

Factors Affecting theForce of Contraction

1. Number of muscle fibers contracting (recruitment)

2. Size of the muscle 3. Frequency of stimulation

4. Degree of muscle stretch when the contraction begins

Muscle Fiber Type: Speed of Contraction

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

• 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 (white)

Force, Velocity, and Duration of Muscle Contraction

Smooth Muscle Tissue • When the longitudinal

layer contracts, the organ dilates and contracts

• When the circular layer contracts, the organ elongates

Smooth Muscle Contractions

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

• Segmentation – contractions and relaxations of smooth muscles that mix substances in the lumen of hollow organs

Peristalsis Animation

Contraction of Smooth Muscle• 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

• 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

Smooth Muscle Tissue • Contracts under the

influence of:

– Autonomic nerves

– Hormones

– Local factors

Developmental Aspects of the Muscular System

• Muscle tissue develops from embryonic mesoderm called myoblasts (except the muscles of the iris of the eye and the arrector pili muscles in the skin)

• Multinucleated skeletal muscles form by fusion of myoblasts

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

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

• Cardiac and smooth muscle myoblasts do not fuse but develop gap junctions at an early embryonic stage

Regeneration of Muscle Tissue

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

• Myoblast-like satellite cells show very limited regenerative ability

• Satellite (stem) cells can fuse to form new skeletal muscle fibers

• 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

Developmental Aspects: Male and Female

• 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

Homeostatic Imbalances

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

Homeostatic Imbalances

Duchenne Muscular Dystrophy:

• Inherited lack of functional gene for formation of a protein, dystrophin, that helps maintain the integrity of the sarcolemma

• Onset in early childhood, victims rarely live to adulthood  

End Chapter 9

Cardiac Muscle Tissue • Striated

• Unicellular

• Branched

• Intercalated discs

Intercalated Discs• Desmosomes

– connect cells• Gap junctions

– Electrical synapses– Excitation spreads rapidly

Smooth Muscle

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

• 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

Smooth Muscle Tissue • No striations (no sarcomeres)

• Uninucleate

• Spindle-shaped

• Involuntary

• May be autorhythmic

• May have gap junctions

Series Elastic Elements

• All of the noncontractile structures of a muscle:–Connective tissue coverings and tendons

–Elastic elements of sarcomeres

Internal load: force generated by myofibrils on the series elastic elements

External load: force generated by series elastic elements on load