BIO 3520 Notes, 2/18/11
SKELETAL MUSCLE
I. Introduction. [Widmaier, pp. 250-251]
A. Function -- Contraction and generation of force.
B. Muscle types. (fig. 9-1)
Skeletal
Cardiac
Smooth
Location
Neural control
Microscopic appearance
II. Skeletal Muscle. [pp. 252-253, 274-275]
A. Over 600 skeletal muscles in the human body (figurea).
1. Makes up 30-40% of body weight.
B. Usually attaches to two bones (fig. 9-27a).
1. Connective tissue attachment to bone
> tendon.2. On contraction, one bone moves.
3. Muscles attached to long bones are in antagonistic pairs.
4. Flexor = A muscle that decreases the joint angle when it contracts
(fig. 9-27b).
5. Extensor = A muscle that increases the joint angle when it contracts.
a Seeley, Stephens, and Tate, Anatomy & Physiology, 2nd ed., 1992.
III. Structure of Skeletal Muscle. [pp. 252-259]
A. Subdivisions of skeletal muscle (figureb).
1. Muscle fiber (fig. 9-2).
a. Single muscle cell.
b. Functional unit of muscle.
c. Cylinder less than 1/10 mm in diameter and up to 1/2 meter long.
d. Fibers run parallel to each other.
2. Fascicle = Bundle of muscle fibers bound by connective tissue.
B. Internal structure of a skeletal muscle fiber (figurec).
1. Cell membrane -- excitable.
2. Multiple nuclei.
3. Myofibrils.
a. Long cylinders, 1 - 2 µm in diameter.
b. Run the length of the fiber.
c. Several hundred to several thousand per fiber.
d. Responsible for contraction.
4. Sarcoplasmic reticulum (fig. 9-11).
a. Network surrounding each myofibril.
b. Storage of calcium ions.
5. Transverse tubules.
a. Link between cell membrane and sarcoplasmic reticulum.
6. Many mitochondria -- provide energy in the form of ATP.
7. Filaments.
a. Each myofibril consists of thousands of tiny filaments.
b. Filaments are made up of contractile proteins.
c. Orderly arrangement of filaments is responsible for striated
appearance.
d. Thin filaments (fig. 9-7).
1. Composed of actin.
2. Two regulatory proteins attached
> tropomyosin andtroponin.
a. Tropomyosin strands lie within the grooves between
two actin chains.
1. Cover binding sites on actin.
b. Troponin complexes occur at regular intervals along
tropomyosin strands.
1. Hold tropomyosin strands in place.
e. Thick filaments (fig. 9-7).
1. Twice as large as thin filaments.
2. Composed of myosin.
3. Each myosin molecule has two globular heads capable of
binding to actin.
4. Tails bundled together with globular heads sticking out.
8. Basis of striated appearance (figs. 9-1a, 9-3).
a. The striated appearance of skeletal muscle is explained by the
orderly arrangement of thick and thin filaments.
b. Thick and thin filaments are arranged in a repeating pattern along
the length of the myofibril -- sarcomere.
1. Sarcomere = Basic subunit of skeletal muscle contraction.
2. Z line forms dividing line between sarcomeres.
3. Sarcomere is 25 µm long.
c. Thick filaments are located in the center of the sarcomere.
1. Make up the A band.
d. Thin filaments extend in both directions from the Z-line.
1. Overlap the thick filaments.
2. Area where there are only thin filaments = I band.
e. In cross-section, each thick filament is surrounded by six thin
filaments arranged in a hexagon (fig. 9-4).
b Widmaier, Raff, and Strang, Vander's Human Physiology: The Mechanisms of Body
Function, 9nd ed., 2004.
c Johnson, M.D., Human Biology: Concepts and Current Issues, 2nd ed., 2003.
IV. Mechanism of Muscle Contraction. [pg. 254]
A. Hugh Huxley and Jean Hanson (1954).
B. Observe what happens when skeletal muscle contracts (figured).
1. Sarcomere --
2. I-band --
3. A-band --
4. Explanation (fig. 9-5) --
d Fox, S.I., Human Physiology, 7th ed., 2002.
V. Innervation of Skeletal Muscle Fibers. [pg. 260]
A. Each muscle fiber is innervated by a single somatic motor neuron.
B. Each motor neuron innervates many muscle fibers, which are distributed
throughout the muscle.
C. Motor unit = One motor neuron and all of the muscle fibers it innervates
(fig. 9-13).
D. Areas of fine neural control have fewer muscle fibers in each motor unit.
1. Extraocular muscles ~ 20 muscle fibers/motor unit.
2. Gastrocnemius muscle ~ 1000 muscle fibers/motor unit.
VI. Neuromuscular Junction. [pp. 259-263, 276-277]
A. Neuromuscular junction = Synapse between a somatic motor
neuron and a skeletal muscle fiber (fig. 9-14a, figuree).
1. Axon terminals of somatic motor neuron contain synaptic vesicles
filled with acetylcholine (ACh) (fig. 9-14b).
2. Motor end plate = Specialized region of muscle cell membrane
across from axon terminal of motor neuron.
a. Contains cholinergic receptors.
B. Mechanism of ACh release is same as the neuron-neuron synapse
(fig. 9-15).
C. Effect of ACh on the motor end plate.
1. ACh binds to cholinergic receptors on motor end plate.
2. Opens ligand-gated cation channels on end plate membrane.
a. Increased permeability to both Na+ and K+.
b. Influx of Na+ is most important
> depolarization.
3. End plate potential (EPP) = Local depolarization of motor end plate.
4. Single EPP is sufficient to trigger an action potential, which spreads
in both directions along muscle cell membrane.
a. Contraction of a skeletal muscle fiber is all-or-none.
5. Question: If EPP is always excitatory, how is muscle contraction
inhibited?
D. Comparison of neuron-neuron synapse and neuromuscular junction.
Neuron-neuron
synapse
Neuromuscular
junction
Neurotransmitters
Graded potential:
Depolarizing
Graded potential:
Hyperpolarizing
Threshold
E. Alteration of neuromuscular transmission by drugs and disease.
1. Botulinum toxin.
a. Produced by bacteria, Clostridium botulinum in improperly
preserved food.
b. Deadly food poisoning (botulism).
c. Blocks release of ACh.
d. Death is from paralysis of respiratory muscles.
e. Botox cosmetic injections (figure).
2. Neuromuscular blocking drugs.
a. South American arrow poison -- curare (figure).
b. Obtained from plants.
c. Kills animals by paralysis.
d. Blocks cholinergic receptors on motor end plate.
e. Used in surgery in conjunction with general anesthesia.
1. Produces complete relaxation of skeletal muscles (including
respiratory muscles).
2. Succinylcholine -- depolarizing neuromuscular blocking drug
(figure).
3. Organophosphates.
a. Various insecticides (ex. malathion) and nerve gases (ex. sarin).
b. Inhibit the enzyme, acetylcholinesterase.
c. Acetylcholinesterase breaks down ACh in the cleft of the NMJ
>terminates action of ACh (fig. 9-15).
d. Involuntary twitching and fasciculations, followed by paralysis and
death.
4. Myasthenia gravis.
a. Destruction of cholinergic receptors on the motor end plate (figure).
b. EPP's are reduced.
c. Muscle weakness.
e Nilsen, L. Behold Man, 1974, pg. 119.
VII. Excitation-Contraction Coupling. [pp. 257-259]
A. Properties of muscle fiber at rest (relaxed).
1. Cytoplasmic Ca++ levels are low (10-7 M).
2. Ca++ is stored in lateral sacs of sarcoplasmic reticulum (fig. 9-11).
3. Tropomyosin is covering binding sites on actin (fig. 9-9a).
4. Troponin is bound to both actin and tropomyosin, holding tropomyosin
in its inhibitory position.
5. Thick and thin filaments are not linked.
6. Muscle is at its resting length.
B. Excitation.
1. Action potential spreads from motor end plate in both directions
along the muscle cell membrane.
2. Action potential travels into interior of cell along transverse tubules.
3. Opens Ca++ channels in sarcoplasmic reticulum (fig. 9-12).
a. Increases cytoplasmic Ca++ concentration (10-5 M).
4. Ca++ binds to troponin
> alters its configuration(fig. 9-9b).
a. Alters configuration of tropomyosin
> uncovers binding siteson actin.
b. Allows myosin to bind to actin.
VIII. Molecular Mechanism of Muscle Contraction. [pp. 254-257]
A. Cross-bridge cycle (fig. 9-8, figuref).
1. Attach -- Myosin binds to actin, forming cross-bridges between
thick and thin filaments.
2. Pull -- Globular heads of myosin tilt toward center of sarcomere,
pulling actin with them (power stroke).
3. Release -- Myosin releases actin and flips back to its original
position.
4. Globular heads reattach to a new site on actin and cross-bridge
cycle is repeated.
B. Role of ATP.
1. ATP binds to myosin to cause release of actin.
2. ATP is then split to form ADP + Pi (bound to myosin)
>energizes the globular head.
3. ADP and Pi are released during the power stroke.
C. Relaxation.
1. When action potentials stop, cytoplasmic Ca++ levels fall.
a. Ca++ is pumped back into the S.R. by primary active transport --
calcium pump (fig. 9-12).
2. Ca++ dissociates from troponin
> troponin and tropomyosin returnto their inhibitory positions.
3. With no cross-bridges, thick and thin filaments return to their resting
positions
> muscle returns to its resting length.
5. Total Ca++ pulse lasts 10 - 100 msec, depending on muscle type.
D. Review.
1. Entire sequence is summarized in table 9-2.
2. Thick and thin filaments slide past each other due to the interaction of
the two contractile proteins, actin and myosin.
3. Requirements for muscle contraction.
a. Calcium ion.
1. High cytoplasmic Ca++ is required for cross-bridge formation
(fig. 9-9).
2. Low cytoplasmic Ca++ causes relaxation.
b. ATP (table 9-1).
1. Provides energy for the power stroke.
2. Binding to myosin causes release of cross-bridges.
3. Drives calcium pump.
4. In death, ATP is depleted.
a. Cross-bridges form, but no power stroke -- rigor mortis
(fig. 9-8)
f Moffett, Moffett, and Schauf, Human Physiology: Foundations & Frontiers, 2nd. ed.,
1993.
IX. Mechanics of Muscle Contraction. [pp. 263-267]
A. Tension vs. load.
1. Muscle contraction involves development of tension.
a. Tension = Force exerted by a muscle contraction.
b. Load = Force required to move an object.
c. Tension and load are opposing forces.
d. To move an object, tension must be greater than load.
2. Isotonic contraction.
a. Muscle develops tension and fibers shorten.
b. Object is moved (figured).
c. Tension > load.
3. Isometric contraction.
a. Muscle develops tension, but fibers do not shorten.
b. Object does not move (figureb).
c. Load > tension.
B. Effect of stimulus intensity.
1. Apply a single electrical pulse to a muscle.
2. If stimulus is large enough (threshold), it will produce a single
contraction or twitch.
a. Threshold = Minimum stimulus required to produce a muscle
contraction.
3. Relaxation time is longer than contraction time (fig. 9-16a).
a. Why? [Hint: Tension is proportional to the cytoplasmic Ca++
concentration.]
4. Increase stimulus intensity
> increase strength of contraction upto a maximum.
5. Dilemma: A single muscle fiber has an all-or-none contraction.
a. How are graded contractions produced in the whole muscle?
6. Recruitment = Increasing muscle tension by increasing the number
of muscle fibers contracting.
C. Effect of stimulus frequency.
1. Rapid contraction and relaxation of a muscle after a single stimulus
is called a twitch.
a. Time required for complete contraction and relaxation is
100 - 200 msec (fig. 9-10).
b. Refractory period of skeletal muscle fiber is 2 msec.
2. Apply repeated electrical pulses to a muscle.
3. At high frequencies, muscle fibers do not have time to relax
completely before the next stimulus.
a. Summation = Repeated, additive contraction of muscle
without full relaxation (fig. 9-19).
b. Tetanus = Smooth, sustained contraction of skeletal muscle
(fig. 9-20).
4. Which type of contraction is seen under physiological conditions?
D. Fatigue = Inability to maintain muscle tension in spite of continued
stimulation (fig. 9-23).
1. Due to depletion of nutrients and ATP.
2. Nerve conduction and muscle action potentials are normal, but
muscle becomes weaker.
E. Length-tension relationship.
1. Increase muscle length
> tension first increases, then decreases(fig. 9-21).
2. Tension declines due to lack of overlap of thick and thin filaments.
3. Normal attachment to bone provides optimum length.
F. Load-velocity relationship.
1. Velocity of maximal muscle contraction is inversely related to load.
2. Increase load
> decrease contraction velocity (fig. 9-18).3. When load > tension, velocity = 0 (isometric contraction).
XI. Sources of Energy. [pp. 267-269]
A. Adenosine triphosphate (ATP).
1. Immediate source of energy for cellular functions.
2. Structure (figureb).
a. Two phosphate groups (PO4) attached by high energy bonds.
3. Reaction (fig. 2-26):
ATP + H2O
> ADP + HPO4= + 7 kcal/mole
4. Majority of ATP is formed in mitochondria.
5. Short-lived source of energy.
B. Creatine phosphate.
1. Immediate reserve of high-energy phosphate groups.
2. Reversible transfer of phosphate groups to ADP (figureb).
Creatine phosphate + ADP <=======> creatine + ATP
3. During muscle contraction, reaction is driven to the right
>creatine phosphate levels fall, while ATP supplies are maintained.
4. After muscle contraction, more ATP is formed by metabolism of
nutrients
> reaction is driven to the left> creatine phosphatelevels rise.
5. Concentration of creatine phosphate in muscle is about 5x that of ATP
> creatine phosphate is depleted in about 30 sec of contraction.
6. Rationale for creatine use by body-builders and athletes.
C. Oxidative phosphorylation (aerobic metabolism).
1. Breakdown of nutrients provides energy to phosphorylate ATP.
2. Requires oxygen.
3. Takes place in mitochondria.
4. Principal fuel -- fatty acids.
5. Major energy source during moderate levels of muscle activity
(up to 70% of maximal).
D. Glycolysis (anaerobic metabolism).
1. Breakdown of carbohydrates.
2. Does not require oxygen.
3. Takes place in cytoplasm.
4. Used during strenuous exercise (greater than 70% of maximal).
5. Relatively inefficient.
6. Produces lactic acid, which contributes to fatigue.
E. Oxygen debt = Depletion of energy reserves during exercise that must
be restored by oxidative phosphorylation.
1. Increased oxygen consumption by muscle cells after exercise.
2. Continued deep breathing and increased cardiac output.
F. Summary (fig. 9-22).
Creatine
phosphate
Oxidative
phosphorylation
Glycolysis
Response time
Principal fuel
Oxygen
requirement
Type of
activity
XII. Skeletal Muscle Fiber Types. [pp. 269-272]
A. Slow-twitch fibers (slow-oxidative).
1. Develop tension relatively slowly (100 msec to peak tension).
2. Able to sustain a contraction for long periods without fatigue.
3. High capacity for aerobic respiration.
B. Fast-twitch fibers (fast-glycolytic).
1. Develop tension rapidly (7 msec to peak tension).
2. Fatigue more rapidly (fig. 9-25, 9-26).
3. Adapted for anaerobic metabolism (fig. 9-24).
Characteristic
Slow-twitch
Fast-twitch
Speed of contraction
Rate of fatigue
Myosin-ATPase activity
Oxygen requirement
Mitochondria
Capillary density
Myoglobin content
Color
C. Third type -- fast-oxidative fibers.
1. Fast twitch, but high oxidative activity.
2. Intermediate in most properties.
D. Summary (table 9-3).
E. Fiber type composition of muscles.
1. Very active muscles contain high proportion of fast-twitch fibers
a. Examples:
2. Postural muscles which contract slowly, but are resistant to fatigue
contain mostly slow-twitch fibers.
a. Examples:
3. Gastrocnemius muscle is about 50:50 (figureb).
F. Fiber type and athletic performance.
1. Twin studies suggest that proportion of FT fibers is genetically
determined.
2. Training does not alter dominant fiber type.
3. Compare strength and endurance of athletes with different proportions
of fiber types.
4. Athlete's choice of sport may be determined, in part, by fiber type
(ex. world-class sprinters -- 60% FT fibers; marathoners -- 20% FT).
XIII. Muscular Adaptation. [pp. 273-274, 276]
A. Atrophy = Decrease in muscle mass and strength.
1. Disuse.
2. Starvation (figure).
3. Aging.
4. Disease.
B. Muscular dystrophy.
1. Progressive degeneration of muscle in young children.
2. Most common form is inherited
a. Sex-linked trait affecting only boys.
3. Discovery of abnormal gene in 1988.
a. Protein called dystrophin is absent.
b. What does dystrophin do? (fig. 9-31a, figure)
C. Hypertrophy = increase in muscle mass and strength.
1. Exercise causes increase in muscle mass and strength.
a. Increase in fiber diameter due to addition of myofibrils.
b. No increase in fiber number.
c. Improved efficiency.
2. Effects of high-intensity, short-duration exercise (ex. lifting weights).
a. Increased fiber diameter, especially FT fibers.
b. Increased number of glycolytic enzymes in FT fibers.
c. Net result: Increased size and strength, no improvement in
endurance.
3. Effects of low-intensity, long-duration exercise
(ex. long-distance running).
a. Little change in fiber diameter.
b. Increased myoglobin content in all fiber types.
c. Increased number of mitochondria in ST fibers.
d. Net result: Little change in size and strength, increased
endurance capacity.
4. Myostatin blockade.
a. Myostatin is a protein that inhibits muscle growth.
b. Genetic mutation produces abnormal myostatin.
c. Recommended reading: “Gene Doping”, Scientific American,
July 2004.
