Physiology Ch. 6 p71-82
Contraction of Skeletal Muscle
-40% of body is skeletal muscle, 10% is smooth and cardiac muscle, with some of the same basic
principles applying to contraction for all types
Skeletal Muscle Fiber – composed of fibers ranging from 10-80um in diameter and made up of smaller
subunits
-fiber extends the length of the muscle, and innervated by one nerve ending.
Organization of Skeletal Muscle- MuscleMuscle FasciculusMuscle FiberMyofibrilSarcomere
Sarcolemma is a Thin Membrane Enclosing Skeletal Muscle Fiber – true cell membrane and an outer
coat made of thin polysaccharide with numerous thin collagen fibrils.
-Sarcolemma fuses with tendon fibers on each end of the muscle, which form bundles to insert on bones
Myofibrils are Composed of Actin and Myosin – each fiber contains thousands of myofibrils, themselves
composed of 1500 adjacent myosin filaments and 3000 actin filaments (responsible for contraction)
-Thick filaments are myosin, thin filaments are actin
-Actin/myosin interdigitate causing myofibrils to alternate between light and dark bands
-Light bands have only actin (I bands because they are isotropic to polarized light)
-Dark bands contain myosin filaments, as well as ends of actin - A bands are anisotropic to polarized light
-Small projections from sides of myosin filaments called Cross-bridges interact with actin -> contraction
-Ends of actin filaments attached to a Z-disc, extending in both directions to interdigitate with myosin
-Z-disc connects multiple myofibrils across the muscle fiber, giving striated appearance to muscle
Sarcomere – portion of myofibril lying between two Z discs (2um in length)
-When muscle is contracted, actin filaments completely overlap myosin – generating greatest force
Titin Filamentous Molecules Keep Myosin and Actin in Place – titin is a filamentous molecule that
maintains side-by-side relationship between myosin and actin (biggest protein in body MW=3million)
-Very springy, act as a framework that holds myosin and actin in place during contraction
-Attached on one end to the Z disk, and tethers to the myosin thick filament, changes length as
sarcomere contracts and relaxes
Sarcoplasm is the Intracellular Fluid Between Myofibrils – spaces between myofibrils filled with
sarcoplasm containing large quantities of K, Mg, P, and enzymes
-Lots of mitochondria present that lie parallel to myofibrils to supply ATP for contraction energy
Sarcoplasmic Reticulum is a Specialized Endoplasmic Reticulum of Skeletal Muscle – surrounding
myofibrils is an extensive reticulum called sarcoplasmic reticulum
Mechanism of Muscle Contraction – occurs in the following steps
1. Action potential travels along motor nerve to nerve ending on muscle fiber
2. Nerve secretes acetylcholine at nerve ending
3. Acetylcholine acts on local area of muscle to open cation channels in membrane
4. Channels allow Na ions to diffuse into interior of muscle, causing action potential at membrane
5. Action potential travels along muscle fiber same way as it travels along nerve
6. Depolarizes muscle membrane causing sarcoplasmic release of Ca2+ ions stored within
7. Ca ions initiate attractive forces between actin and myosin sliding towards each other
8. Ca pumped back into sarcoplasmic reticulum by Ca membrane pump until new potential
Molecular Mechanism of Muscle Contraction
-In relaxed state, ends of actin filaments extending from two successive Z disks barely overlap, but
overlap a great deal in the contracted state
-Z discs pulled by actin up to the ends of myosin, thus contraction occurs by sliding filament mechanism
-Forces generated by interaction of cross-bridges from myosin filaments with actin filaments using ATP
Molecular Characteristics of Contractile Filaments – myosin filaments are composed of multiple myosin
molecules
-myosin composed of 6 polypeptide chains, two heavy chains (200kDa) and 4 light chains (20kDa)
-heavy chains wrap spirally around each other in double helix called tail of molecule
-one of each heavy chains is folded bilaterally into globular polypeptide called myosin head
-four light chains also part of the head (2 in each head) to help control head during contraction
-myosin filament composed of 200 myosin molecules, tails form the body, heads hang out towards sides
-part of body hangs to side creating an arm to extend head outward – together called Cross-Bridge
-each cross bridge flexible at two points called hinges – one where arm leaves body and the other where
head attaches to arm
-hinged arm allows heads to be either extended far outward from body of myosin filament or close
-total length of myosin filament is exactly 1.6um, no cross bridged heads in center
ATPase Activity of Myosin Head – myosin head functions as an ATPase enzyme during contraction
Actin Filaments are Composed of Actin, Tropomyosin, and Troponin – backbone of actin is double
stranded f-actin with 2 light strands wound in a helix
-F-actin is composed of single units of G-actin each weighing 42kDa, attached to ADP
-Bases of actin filaments are inserted strongly into Z discs
Tropomyosin – actin filament contains tropomyosin weighing 70kDa that wrap spirally around actin
-in a resting state, tropomyosin lie on top of active sites actin strands so attraction between actin and
myosin cannot occur
Troponin – intermittently among tropomyosin are protein molecules called troponin, 3 loosely bound
protein subunits (troponin I, T, and C)
Troponin I – affinity for actin
Troponin T – affinity for tropomyosin
Troponin C – affinity for calcium
-attaches tropomyosin to actin
Interaction of Myosin, Actin, and Calcium to Cause Contraction – a pure actin filament without
troponin-tropomyosin binds instantly and strongly to myosin heads, addition of troponin-tropomyosin
prevents binding of actin/myosin.
-active sites on normal actin of relaxed muscle are inhibited or covered by troponin-tropomyosin
-before contraction can take place, troponin-tropomyosin must be inhibited
-calcium inhibits troponin-tropomyosin by binding to troponin C (4 binding sites) causing it to undergo a
conformational change uncovering active sites allowing attraction with myosin
Walk-Along Theory of Contraction – soon as actin becomes activated by calcium, heads of cross-bridges
from myosin become attracted to active sites on actin, causing contraction to occur by walk along
method
-heads of two cross-bridges attaching to and disengagiong from active sites on actin.
-when head attaches to active site, the attachment causes changes in forces between head and arm of
cross-bridge causing head to tilt toward arm and drag actin with it. Tilt is called Power Stroke
-after tilting, head automatically breaks away from active site and returns to extended direction,
beginning a new power stroke, moving another step
-each cross-bridge believed to act independently, greater number of cross-bridges the greater the force
of contraction
ATP as the Source of Energy for Contraction – large amounts of ATP are cleaved during contraction, and
the greater the work performed by muscle, the more ATP is required – called the Fenn Effect
1. Heads of cross-bridges bind with ATP; myosin head cleaves ATPADP + Pi bound to head,
extending the head perpendicularly toward actin by not attached to myosin
2. Troponin-tropomyosin binds calcium, opening active sites on actin to bind with myosin
3. Bond between head and active site on actin causes conformation change, tilting head toward
arm to provide power-stroke for pulling actin filament
a. Energy for power stroke is from the stored energy “cocked spring” by conformational
change that occurred earlier when ATP was cleaved at the head
4. After the tilt, ADP + Pi are released from the head and a new ATP binds causing detachment of
head from actin
5. New ATP is cleaved to begin the next cycle leading to new power stroke, energy cocks the head
back to its perpendicular condition
6. When cocked head binds with new active site, it becomes uncocked and provides power stroke
7. Proceeds until actin pull Z membrane up against ends of myosin or load becomes too great
Amount of Actin and Myosin Filament Overlap Determines Tension Developed by Contracting Muscle
-Tension in muscle is 0 when actin filament has pulled all the way out to the end of myosin causeing no
overlap
-as sarcomere shortens and actin filament begins to overlap, tension increases progressively
until reaching 2.2um, when actin has overlapped all cross bridges by not reached center of
myosin
-further shortening retains full tension until around 2um, when two actin filaments begin to
overlap each other, causing additional overlap with myosin, strength of contraction decreases
rapidly
-the two Z discs at ends of myosin filaments, shortening crumples myosin and strength
of contraction goes down to 0
Effect of Muscle Length on Force of Contraction in Whole Intact Muscle – whole muscle has a lot of
connective tissue in it, and sarcomeres do not always contract the same amount, same general form for
normal range of contraction.
-When muscle is normal resting length, it contracts upon activation with maximum force of contraction
-Increase in tension that occurs during contraction (Active Tension), decreases as muscle is stretched
beyond normal length
Relation of Velocity of Contraction to Load – muscle contracts rapidly when there is no load in 0.1s.
When loads are applied, contraction slows down as load increases. When load is equal to maximum
force of contraction, velocity slows to 0.
Work Output During Muscle Contraction – When muscle contracts, it performs work; energy is
transferred from muscle to external load: W = L x D
Sources of Energy for Muscle Contraction – contraction depends on ATP for the walk along mechanism
where cross-bridges pull actin filaments
-Small amount of ATP required for pumping Ca ions from sarcoplasm into sarcoplasmic reticulum after
contraction is over, and pumping Na and K ions through muscle fiber membrane to maintain ionic
environment
-First source of energy that is used to reconstitute ATP for contraction is Phosphocreatine – which
carries a phosphate bond similar to ATP but has a higher energy bond used to turn ADP  ATP
-Combined energy from ATP + phosphocreatine can only sustain maximal contraction 5-8s
-Glycolysis of Glycogen stored in skeletal muscle is used to reconstitute both ATP and phosphocreatine
-Enzymatic breakdown of glycogen to pyruvic acid and lactic acid liberates energy used to
convert ADP  ATP
-Glycolysis is important because it can occur without oxygen, so that contraction can occur for a
little without O2, and that the rate of formation of ATP is 2.5 times as rapid from glycolysis as
opposed to ATP formation in response to cellular foodstuffs reacting with oxygen
-Third source of energy is Oxidative Metabolism – combining O2 with end products of glycolysis to
liberate ATP: derives 95% of energy for muscle contraction
Efficiency of Muscle Contraction – muscle efficiency is very low (25%) because ½ of energy in food is
lost during formation of ATP, and 45% of energy in ATP is converted to work
-Maximal efficiency occurs during moderate velocity contraction (30% of maximum)
-Too slow and heat is released as maintenance work, too fast and too much energy is released
to overcome viscous friction within muscle
Characteristics of Whole Muscle Contraction – characteristics of muscle contraction can be elicited by
single muscle twitches – instantaneous excitation of nerve to a muscle giving rise to single contraction
-Isometric Contraction – Muscle does not shorten (used when comparing muscle types)
-Isotonic Contraction – Muscle shortens but tension remains constant
Characteristics of Isometric Twitches from Different Muscles – because humans have differences in
muscle sizes between different muscles
-Gastrocnemius muscle has duration of contraction of 1/15s, soleus has duration of 1/5s
-Ocular movements must be rapid to maintain fixation of eyes on objects, and gastrocnemius muscle
must contract moderately rapidly to provide sufficient velocity of limb for running/jumping
-Soleus is slower contracting to deal with long-term support of body against gravity
Fast vs Slow Muscle Fibers – every muscle in body is composed of fast and slow fibers
-Fast fibers such as anterior tibialis react rapidly
-Slow fibers such as soleus respond slowly with prolonged contraction
Slow Fibers (Type I, Red Muscle)
Fast Fibers (Type II, White Muscle)
Small Fibers
Large Fibers
Smaller Nerve Fibers
Extensive Sarcoplasmic Reticulum- Fast Ca Release
Extensive Vasculature for Oxygen
Less Extensive Vasculature
Many Mitochondria
Fewer Mitochondria
High Myoglobin to Store O2
Low Myoglobin
High Glycolytic Enzymes for Rapid Energy
Motor Unit – all muscle fibers innervated by single nerve fiber, one nerve fiber leaving spinal cord can
innervate multiple muscles
-small muscles tend to have more nerve fibers per muscle fiber (2-3 muscle fibers per motor unit)
-large muscles like soleus do not need fine motor control and can have hundred fibers in single unit
Muscle Contractions of Different Force – “Summation” means adding together individual twitch
contractions to increase overall intensity of contraction
-summation occurs by increasing number of motor units contracting simultaneously and increasing
frequency of contraction (Frequency Summartion) can lead to Tetanization.
Multiple Fiber Summation – CNS sending weak signal for contraction, smaller motor units of muscle
may be stimulated in preference to larger units. As strength increases, larger units begin to be excited
-Large fibers have up to 50x contractile force as small fibers – Size Principle
-different motor units are driven asynchronously by spinal cord, so contraction alternates between
motor units one after the other, providing smooth contraction
Frequency Summation and Tetanization – As frequency increases, there comes a point where each new
contraction occurs before preceding one is over, second contraction added to first, so total strength
increases progressively with increasing frequency.
-Frequency will reach critical level and contractions fuse together to form smooth contraction, which is
called tetanization
-any increase in frequency has no effect because Ca ions are maintained in sarcoplasm
Maximum Strength of Contraction – max strength of contraction at normal muscle length is (50lbs/in)
or 3-4kg/cm2.
-Quad tendon has 16in2 of muscle belly, it can tense up to 800lbs on patellar tendon
-After period of rest, initial strength of contraction is ½ of its strength 10-50 twitches later. Contraction
increases until a plateau, called the staircase effect (treppe)
-believed to be caused by increasing Ca ions in cytosol due to release from sarcoplasmic
reticulum with each successive muscle potential and failure to recapture ions immediately
Skeletal Muscle tone – certain amount of tension exists in muscle (tautness) even at rest, called the
muscle tone.
-results from low rate of nerve impulses from spinal cord from brain and out to muscle spindles
Muscle Fatigue – Prolonged contraction of muscle leads to muscle fatigue
-fatigue increases directly with depletion of muscle glycogen, therefore fatigue results from inability of
contractile and metabolic processes of muscle to supply the same work
-Transmission of nerve signal also diminishes after activity
-Interruption of blood flow through contracting muscle leads to fatigue within 1-2 min
Lever systems of body – muscles operate by applying tension to points of insertion
-biceps has cross sectional area of 6 square inches, max contractile force of 300 pounds
-at 90 degree angle of arm, attachment is 2 inches anterior to elbow and length of level is 14 inches
-lifting power is 1/7th of 300 pounds, or 43 pounds,
-When fully extended, attachment of biceps much less than 2in anterior and contraction is <43 pounds
-Lever system analysis depends on: point of muscle insertion, distance from fulcrum of lever, length of
lever arm, position of lever.
Position of body part by Contraction of Agonist and Antagonist Muscles – all body movements are
caused by simultaneous contraction of agonist/antagonist muscles
-if leg is to be placed in midrange, agonist and antagonist muscles excited equally
-maximum force of contraction at elongated muscle, therefore, elongated muscle on one side of joint
can contract with much greater force than shorter muscle on opposite side
-As arm or leg moves toward midposition, strength of long muscle decreases, and strength of short
muscle increases
Remodeling of Muscle to Match Function – muscles constantly remodeled to match functions
-diameters, lengths, strengths vascular supplies, and types of fibers can be alteres
-When total muscle mass increases, it is called hypertrophy, when it decreases it is called atrophy
-Hypertrophy results from increase in actin/myosin filaments in each fiber – Fiber Hypertrophy
-Atrophy results from unused muscle, where degradation of contractile proteins is more rapid than rate
or replacement
-Degrades through ATP-dependent ubiquitin-proteosome pathway
Adjustment of Muscle Length – a form of hypertrophy occurs when muscles are stretched to greater
than normal length, new sarcomeres are added
-shortened muscles can have sarcomeres removed
-under extreme force generation, actual number of muscle fibers increase – Fiber Hyperplasia
Effects of Muscle Denervation – when muscle loses nerve supply, it no longer receives nerve signal
required to maintain normal muscle size – atrophy begins immediately
-after 2 months, degenerative changes occur in fibers themselves
-If nerve grows back, functional return happens in 3 months, if return doesn’t happen, chance that it will
becomes less and less, up to 1-2 years when no return will occur
-In final stage of atrophy, muscle fibers are replaced with fibrous and fatty tissue
-Fibrous tissue has tendency to shorten, called contracture
Recovery of Muscle Contraction in Poliomyelitis – polio destroys some but not all nerve fibers.
Remaining fibers branch off and form new axons to innervate paralyzed muscle fibers
-causes large motor units called Macromotor units, containing 5x the normal muscle fibers per unit
-Decreases fitness of muscles but does allow partial recovery
Rigor Mortis – Several hours after death, muscles of body go into state of contracture where muscles
contract and become rigid even without action potentials
-results from loss of ATP, which is required to cause separation of cross-bridges from actin filaments
during relaxation
-Muscles remain in rigor until muscle proteins deteriorate 15-25 hours later from autolysis from
lysosomes, everything occurs rapidly at higher temperatures