Updated Notes On Physiology

UNIT II: MUSCLE PHYSIOLOGY
Muscle Overview
● Three types of muscle tissue which differ in structure, location, function and means of activation:
o Skeletal o Cardiac o Smooth
Muscle Similarities
● Skeletal and smooth muscle cells are elongated and are called muscle fibers
● Muscle contraction depends on two kinds of myofilaments – actin and myosin
● Muscle terminology is similar
o Sarcolemma – muscle plasma membrane
o Sarcoplasm – cytoplasm of a muscle cell
o Sarcoplasmic reticulum – modified, highly specialized endoplasmic reticulum
o Prefixes – myo, mys, and sarco all refer to muscle
Skeletal Muscle Tissue: striated, skeletal, & voluntary

● Location: attached to skeletons
● Shape: elongated, cylindrical
● Muscle fibers: Longest; cigar-shaped
● Size: Largest muscle
● Nuclei: multinucleated; peripheral
● Has obvious stripes called striations (striated muscle)
● controlled voluntarily (i.e., by conscious control) but can be activated by reflexes
● Contracts rapidly but tires easily
● responsible for overall body motility
● extremely adaptable & exert forces ranging from a fraction of an ounce to over 70 pounds
Cardiac Muscle Tissue: cardiac, striated, involuntary

● Location: heart – bulk of heart walls & roots of large blood vessels only
● Shape: elongated, cylindrical that branch
● Nuclei: uninucleate & central
● Is striated like skeletal muscle but is not voluntary
● Contracts at a fairly steady rate set by the heart’s pacemaker
● Neural controls allow the heart to respond to changes in bodily needs
Smooth Muscle Tissue: visceral, non-striated, & involuntary

● Location: lining walls of hollow visceral organs
▪ alimentary: stomach
▪ respiratory passages: bronchus/bronchioles
▪ urogenital tract: urinary bladder/uterus
▪ blood vessel walls
● Shape: spindle-shaped, elongated
● Nuclei: uninucleate & central
● Arranged in layers: inner circular/outer longitudinal
● Slow, sustained contraction
o “housekeeper”
● Forces food and other substances through internal body channels
Muscle Functions
● Movement
o Skeletal muscles – responsible for all locomotion, manipulation, respond quickly to external
environment & facial expressions
o Cardiac muscle – responsible for coursing the blood through the body
o Smooth muscle – helps maintain blood pressure; & squeezes or propels substances (i.e., food, feces)
through internal body channels
SU-IRSPT(PT12A/15)mvtsymd™2018
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● Maintains Posture & Body Position – maintains erect, upright position despite pull of gravity
● Stabilize joints
● Generates heat – as a by-product of muscle activity from ATP used to power muscle contraction
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Other Important Muscle Functions:
● Smooth muscles:
o form valves that regulate the passage of substances through internal body openings
o dilate & constrict the pupils of our eyes
o make up the arrector pili muscles that cause our hairs to stand on end.
● Skeletal muscles:
o form valves that are under voluntary control
o enclose & protect fragile internal organs.
COMPARISON OF SKELETAL, CARDIAC, SMOOTH MUSCLE

]Table 9.4. pp. 310-311. Chapter 9. Muscles & Muscle Tissue Elaine N. Marieb. Human Anatomy & Physiology. 5th ed.]
[Table 6.1. p.182. Chapter 6. Muscular System. E.N. Marieb. Essentials of Human A&P 12th ed.]
CHARACTERISTICS SKELETAL CARDIAC SMOOTH

Attached to bones, Hollow visceral organs
Body location Walls of heart
facial muscles, skin (except heart)
Single, very long,
Branching chains of cells,
Cell shape & cylindrical, multinucleate Single, fusiform,
uninucleate, striations,
appearance cells uninucleate, no striations
intercalated discs
with obvious striations
Epimysium, perimysium Endomysium attached to
Connective tissue components Endomysium
& endomysium fibrous skeleton of heart
NO, but actin & myosin
Presence of myofibrils composed Yes, but myofibrils are filaments are present
Yes
of sarcomeres irregular thickness throughout; dense bodies
anchor actin filaments
Yes; one in each sarcomere
Presence of T-tubules & site of Yes; two in each sarcomere
at Z disc; larger than NO; only caveoli
invagination at A-I junction
those in skeletal muscle
Less than skeletal muscle Equivalent to cardiac muscle
Elaborate sarcoplasmic
Yes (1-8% of cell volume); scant (1-8% of cell volume); some
reticulum
terminal cisternae SR contacts the sarcolemma
Presence of gap junctions No Yes, at intercalated discs YES, in single-unit muscle
Cells exhibit individual Not in single-unit muscle;
YES NO
neuromuscular junctions YES in multi-unit muscle
Voluntary; Involuntary, Involuntary;

Regulation of via axonal endings of the the heart has a pacemaker; autonomic nervous system
contraction somatic nervous system autonomic nervous system controls; hormones,
controls controls; hormones; stretch chemicals, stretch
Source of Ca2+ for Sarcoplasmic
SR & from the ECF SR & from the ECF
calcium pulse reticulum (SR)
Site of Troponin on actin- Troponin on actin-containing Calmodulin on myosin-
calcium regulation containing thin filaments thin filaments containing thick filaments
Presence of Yes
No YES
pacemaker(s) (in single-unit muscle only)
Effect of nervous
Excitation Excitation or inhibition Excitation of inhibition
system stimulation
Speed of contraction Slow to fast Slow Very slow
Rhythmic contraction No Yes Yes, in single-unit muscle
Contractile strength Contractile strength

Response to stretch increases with degree of increases with degree of Stress-relaxation response
stretch (to a point) stretch
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Respiration Aerobic & anaerobic Aerobic Mainly aerobic
MUSCLE PHYSIOLOGY: SKELETAL MUSCLE

(please refer to the following references: fig. 6.4, pg.75. Chapter 6. Guyton & Hall. Textbook of Medical Physiology. 11 th ed.; fig. 6.3, pg.
186, E.N. Marie/S.M. Keller. Essentials of Human Anatomy & Physiology 12th ed.; fig. 6.6, pg.192. E.N. Marieb. Essentials of Human
Anatomy & Physiology 9th ed.)
Physical Structure and Function

● 40% of the body mass
● Numerous fibers which extends the entire length of the muscle
● Each muscle is a discrete organ composed of muscle tissue, blood vessels, nerve fibers, and connective
tissue
● Three connective tissue sheaths are:
o Endomysium – fine sheath of connective tissue composed of reticular fibers surrounding each muscle
fiber
o Perimysium – fibrous connective tissue that surrounds groups/bundle of muscle fibers called fascicles
o Epimysium – an overcoat of dense, tough, regular connective tissue that surrounds the entire muscle
Nerve and Blood Supply

● Each muscle is served by one nerve, an artery, and one or more veins
● Each skeletal muscle fiber is supplied with only one nerve ending that controls contraction
● Contracting fibers require continuous delivery of oxygen and nutrients via arteries
● Wastes must be removed via veins
Attachments
● Most skeletal muscles span joints and are attached to bone in at least two places
● When muscles contract the movable bone, the muscle’s insertion moves toward the immovable bone,
the muscle’s origin
● Muscles attach:
o Directly – epimysium of the muscle is fused to the periosteum of a bone
o Indirectly – connective tissue wrappings extend beyond the muscle as a tendon or aponeurosis
Microscopic Anatomy of a Skeletal Muscle Fiber/Cell

● Each skeletal muscle fiber is long, huge, cylindrical, cigar-shaped cell with multiple nuclei just beneath
the sarcolemma
● Fibers are 10 to 100 m in diameter, and up to hundreds of centimeters long
● Each cell is a syncytium produced by fusion of embryonic cells
SARCOLEMMA – cell membrane / plasma membrane surface

● Thin outer layer of polysaccharide material containing numerous thin collagen fibrils
● At the end of each muscle fiber, fuses with a tendon fiber
● Tendon fibers collect into bundles & form muscle tendon that insert into the bone
SARCOPLASM – cytoplasm with little cytosol

● contain usual intracellular constituents & organelles
● Has numerous glycosomes (glycogen granules) and a unique oxygen-binding protein called myoglobin
● Has numerous mitochondria lies parallel to the muscle fiber
MYOGLOBIN – red protein pigment that stores oxygen within the muscle cells
SPECIALIZED STRUCTURES in the Sarcoplasm:

● Myofibrils – main intracellular structures
o makes up bulk of sarcoplasm; nearly fill up the sarcoplasm
o consist of bundles of contractile & elastic proteins responsible for contraction
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● Sarcoplasmic reticulum – modified, specialized smooth endoplasmic reticulum
● T tubules (transverse tubules) – Branching network of transverse tubules closely associated with the
terminal cisternae of the sarcoplasmic reticulum
o modification of the sarcolemma
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MYOFIBRILS – densely packed, long, rod-like, ribbon-like contractile elements that run parallel the entire
length of the muscle cell
● makes up (80%) most of the skeletal muscle volume
● contractile elements of the skeletal muscle cells
● Each myofibril is composed of several types of proteins:
o Myosin – thick filament proteins
o Actin – thin filament proteins
o Troponin & tropomyosin – regulatory proteins
o Titin & nebulin – accessory proteins
● arranged in a perfectly aligned repeating series of dark A bands and light I bands giving the striated
appearance/banding pattern
SARCOMERE – “muscle segment”; smallest contractile unit of a muscle

● chain of contractile units in the region of a myofibril between two successive Z discs
● Composed of one repeat pattern of myofilaments made up of contractile proteins
Elements of a Sarcomere – Banding Patterns: reveals the working structure of the myofibrils.
● myofibrils are chains of tiny contractile units called sarcomeres
o Sarcomeres are aligned end to end like boxcars in a train along the length of the myofibrils.
● the precise arrangement of the myofilaments (smaller structures within sarcomeres that produces the
striations in skeletal muscle fibers.
nebulin
Z disc – “Z” zwischen (German – between); coin-shaped sheet of proteins (connectins)

● a darker area in the middle of the light I band
● Zigzag structures as attachment site of thin actin filaments
● anchors the thin filaments and connects myofibrils to one another
● Two (2) Z discs + myofilaments between = One (1) sarcomere
I band – “I” isotopic (reflects light uniformly under polarized microscope); Light colored bands
● Thin actin filaments
● Z disc run through the middle of an I band, so each half of I band belongs to two (2) different
sarcomere
A band – “A” anisotopic (an – not; scatter light unevenly); darkest bands
● Entire length of thick filament
● Outer edges, thick & thin filament overlap
● the center is occupied by thick filaments only
H zone – “H” helles (German – clear); “bare region”

● Central region of A band; a lighter area in the center of dark A band
● Lighter than outer edges of A band
● Occupied by thick filaments only
M line – “M” mittel (German – middle)

● Represent attachment site for thick filaments (equivalent to Z disc for thin filament)
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● is in the center of the H zone
● One (1) A band divided in half by an M line
MYOFILAMENTS – smaller units within sarcomere; responsible for the banding pattern of myofibril
● Two types of threadlike protein within a sarcomere:
o Thick myofilaments– made-up of bundled molecules of Myosin
▪ extends the entire length of the dark A band
o Thin myofilaments – composed of contractile proteins Actin
▪ extends across the I band & partway into the A band
▪ contains regulatory proteins: Troponin & Tropomyosin
● Thin actin filaments do not overlap thick myosin filaments in the lighter H zone
● M lines appear darker due to the presence of the protein desmin
ACCESSORY ELASTIC PROTEINS: Titin & Nebulin Molecules
TITIN molecules – huge, giant, filamentous proteins

● Elastic, “springy” molecule
● Extends from Z disc to the next M line
● does not resist stretching in ordinary range of extension
o Stiffens the more when it uncoils which resists excessive stretching that might pull the sarcomeres
apart.
● functions:
o Stabilize the position of the contractile filaments
o attaches the thin myosin filaments to the Z-disc
o act as framework that lines up the myosin & actin filaments to make the contractile machinery of the
sarcomere work
o Its elasticity returns stretched muscle to their resting length
▪ part of the titin that spans the I band is extensible that unfolds when the muscle is stretched & recoils
when the tension is released which contributes to the cell’s ability to spring back into shape after being
stretched
o Acts as template for initial formation of portions of contractile filaments of the sarcomere, especially
myosin filaments
NEBULIN molecules – inelastic giant protein

● Lies alongside thin filaments & attaches to the Z disc
● helps align actin filaments of the sarcomere
Ultrastructure & Molecular Composition of Myofilaments: MYOSIN & ACTIN FILAMENTS
Thick Filaments – composed of the bundled protein MYOSIN

● Extends from the entire length of A band
● Contain ATPase enzymes – splits ATP into ADP + Pi & generate power for muscle contraction
● Middle parts are smooth; ends studded with projections (Myosin heads)
● Each myosin molecule has a rod-like tail & two globular heads
o Tails – two interwoven, heavy polypeptide chains
o Heads – two smaller, light polypeptide chains called cross – bridges to link the thick with the thin
filaments during contraction.
▪ “business end” of myosin
● are attached to the Z discs by titin molecule
o TITIN – elastic filaments that run through the core of the thick filament.
Thin Filaments – chiefly composed of the contractile protein ACTIN

● Contains regulatory proteins that allows (or prevent) myosin head-binding with actin
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o Troponin & Tropomyosin
● Anchored to Z discs
● Each actin molecule is a helical polymer of globular subunits called G actin
o The subunits contain the active sites to which myosin heads attach during contraction
o polymerized into long actin filaments (13 G actin / strand of the helix)
● backbone of each thin filament appears to be formed by an actin filament that coils back on itself
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Regulatory Proteins: Tropomyosin & Troponin
TROPOMYOSIN – rod shaped protein with two (2) strands wrapped around the sides of the actin helix & helps
to stiffen the actin core
● successive molecules are arranged end-to-end along the actin filaments
● in the relaxed/resting state, lies on top of the active sites on the actin strands so that attraction
between actin & myosin filaments does not occur to cause contraction
● blocks the active sites on actin & prevents the myosin heads to bind with the thin filaments
TROPONIN – attached along the sides of tropomyosin molecule

● Complex of three (3) loosely bound polypeptide protein subunits:
o TROPONIN I (TnI) – inhibitory subunit with strong affinity to actin
o TROPONIN T (TnT) – strong affinity to tropomyosin & helps position it on actin
o TROPONIN C (TnC) – strong affinity to calcium ions
SARCOPLASMIC RETICULUM (SR) – Elaborate, highly specialized smooth endoplasmic reticulum

● The interconnecting tubules & sacs of the SR runs longitudinally & surround each myofibril
● Interconnecting tubules & cisternae (sacs) form perpendicular cross channels
● Functions in the regulation of intracellular calcium levels – stores calcium & release on demand when
muscle fiber is stimulated to contract
T Tubules (transverse tubules) – continuous with the sarcolemma

● penetrate into the cell’s interior at each A band–I band junction
● conduct impulses to the deepest regions of the muscle which signal for the release of Ca2+ from
adjacent terminal cisternae of SR
● T tubules runs between the paired terminal cisternae to form triads (successive groupings of the three
membranous structures: terminal cisternae, T tubules, terminal cisternae)
Triad Relationships:
o T tubules & SR provide tightly linked signals for muscle contraction
o A double zipper of integral membrane proteins protrudes into the inter-membrane space
o T tubule proteins act as voltage sensors
o SR foot proteins are receptors that regulate Ca2+ release from the SR cisternae
Figure
CHECK THE FOLLOWING LINKS IN YOUTUBE (for additional reference on SKELETAL MUSCLE CONTRACTION):
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https://youtu.be/BVcgO4p88AA
MUSCLE PHYSIOLOGY: Skeletal Muscle
STIMULATION & CONTRACTION OF SINGLE SKELETAL MUSCLE FIBERS

General Mechanism of Skeletal Muscle Contraction
Molecular Mechanism of Muscle Contraction: Sliding Filament Theory / Walk-Along Theory
SKELETAL MUSCLE CONTRACTION

● Remarkable process that allows to create force to move or resist load
● Muscle tension – is the force created by muscle contraction
● Load – is a weight or force that opposes contraction of muscle
● “shortening” = contraction  activation of myosin cross-bridges
o Shortening occurs when the force or tension generated by the myosin cross-bridges on the thin
filaments is more than the forces opposing shortening
● RELAXATION = end of contraction  when cross-bridges becomes inactive & tension generated
declines
● Active process requiring energy: ATP
● In order to contract, a skeletal muscle must:
o Be stimulated by a nerve ending
o Propagate an electrical current or action potential, along its sarcolemma
o Have a rise in intracellular Ca2+ levels, the final trigger for contraction
Functional Characteristics of Muscle Tissue

● Excitability, or irritability / responsiveness – the ability to receive & respond to a stimulus
● Contractility – the ability to forcibly shorten/contract when stimulated (sets muscles apart from other
tissues)
● Extensibility – the ability to be stretched or extended beyond resting length when relaxed
● Elasticity – the ability to recoil & resume the original resting length after being stretched
Major Steps in Skeletal Muscle Contraction:
1. Events at the neuromuscular junction – converts chemical signal from somatic motor neuron into
electrical signals in the muscle fiber.
2. Excitation–contraction coupling – a process in which muscle action potentials initiate calcium signals
which activate the contraction–relaxation cycle.
● Link between electrical signal to muscle contraction
3. Contraction–relaxation cycle – at the molecular level can be explained by the sliding filament theory of
contraction.
o Muscle twitch – is one contraction–relaxation cycle in normal muscles
The General Mechanism of Skeletal Muscle Contraction:

● An action potential travels along a motor nerve to its axonal nerve endings on muscle fibers.
● At each nerve ending, the nerve secretes a small amount of neurotransmitter – acetylcholine (ACh) –
released it into the neuromuscular junction.
● ACh acts on a local area of the muscle fiber membrane by attaching to membrane protein receptors on
the sarcolemma to open multiple ACh-gated protein channels
● Opening ACh-gated membrane protein channels allows sodium ions to flow into the interior of the
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muscle fiber membrane initiating an action potential.
● Action potential travels along the muscle fiber membrane.
● Action potential depolarizes the muscle membrane, down deep into the muscle fiber & release calcium
ions from the sarcoplasmic reticulum.
● Muscle contraction occurs.
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Molecular Mechanism of Skeletal Muscle Contraction: Sliding Filament Theory of Contraction
(please refer to the following references: fig. 6.4, pg.75. Chapter 6. Guyton & Hall. Textbook of Medical Physiology. 11 th ed.; fig. 9.5, pg.
285, E.N. Marie. Essentials of Human Anatomy & Physiology 5th ed.; fig. 6.6, pg.192. E.N. Marieb. Essentials of Human Anatomy &
Physiology 9th ed.; fig.6.8, pg.192 E.N. Marieb Essentials of Human Anatomy & Physiology 12th ed.)
SLIDING FILAMENT THEORY OF SKELETAL MUSCLE CONTRACTION

● 1954. Hugh Huxley
● states that Thin filaments slide past the thick ones so that the actin and myosin filaments overlap to a
greater degree in an energy–requiring process  muscle contraction
● Thin & thick filaments do not change length or shorten but slide past each other.
o In the relaxed state, thin & thick filaments overlap only slightly.
o In contracted state, the actin filaments have been pulled inwards among the myosin filaments with
their ends overlap one another.
● Upon stimulation by the nervous system, myosin heads bind to active sites on actin filaments & sliding
begins.
● RELAXED State: Large I band (thin filaments only) and A band whose length is the length of the
thick filament
o Each myosin head binds & detaches several times during contraction, acting like a ratchet to generate
tension and propel the thin filaments to the center of the sarcomere
● PARTIALLY Contracted State: As contraction occurs, sarcomere shortens. The two Z discs at each end
move closer together while the I band and the H zone almost disappears. These are regions where actin &
myosin do not overlap in resting muscle.
o Z discs have been pulled by the actin filaments toward the ends of the myosin filaments
o Distance between Z discs is reduced, the I band shorten, the H zones disappear, & the A bands move
closer together but do not change in length
o As this event occurs throughout the sarcomeres, the muscle shortens
● FULLY Contracted State: Despite shortening of sarcomere, A band length remains constant.
Sliding of thin actin filaments along thick myosin filaments as actin filaments move toward the M line in the
center of the sarcomere. The force that pushes the actin filament is the movement of myosin cross bridges that
link actin & myosin.
Molecular Mechanism of Skeletal Muscle Contraction

● ? What FORCE causes actin filament to slide inward among myosin filaments.
o Mechanical forces generated by the interaction of the myosin cross bridges that link actin & myosin
filaments
▪ In a polarized resting state, this interaction does not occur.
o With an action potential propagated along the membrane cause SR to release calcium ions & in the
presence of ATP  muscle contraction occurs.
ACTIN FILAMENT: Role of the Troponin-Tropomyosin Complex on the Inhibition & Activation by
Calcium Ions
● Actin filament binds instantly & strongly with heads of the myosin molecules in the absence of
troponin – tropomyosin complex.
● Troponin – tropomyosin complex inhibits & physically covers the active binding sites of the actin
filament
o Actin active binding sites cannot attach to the heads of the myosin filaments to cause contraction
● Calcium ions inhibits the inhibitory effect of troponin–tropomyosin complex on the actin filament
o Unknown mechanism
o In a relaxed / polarized state (normally) – troponin subunit TnC binds with 2 calcium ions
o When stimulated to contract (with adequate nerve stimulus) – calcium ions are released from the
sarcoplasmic reticulum increasing the calcium ion levels/concentration in the sarcoplasm  calcium ions bind
with troponin C (4:1)  conformational change occurs with the troponin complex pulling the tropomyosin
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molecule deep into the groove between the two actin strands.  active binding sites on actin molecule are
exposed/uncovered  attracting myosin heads to attach with the actin filament  muscle contraction occurs
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The Role of Ionic Calcium (Ca2+) in Skeletal Muscle Contraction Mechanism
● When a nerve impulse reaches the sarcolemma of a skeletal muscle fiber, an action potential is
initiated & generated
o An action potential is transmitted deep into the muscle cell along the T tubules  stimulates the
sarcoplasmic reticulum (SR) to release CALCIUM ions into the sarcoplasm  increasing the intracellular
concentration of Ca2+
o Increase intracellular Ca2+ concentration (within the sarcoplasm)  molecular changes in the troponin-
tropomyosin complex on the actin molecule occurs  actin active binding sites are exposed  myosin cross-
bridge formation occurs with the actin filament  muscle contraction
● When an action potential ends  Ca2+ are immediately reabsorbed back into the SR  muscle relaxation
● At low intracellular Ca2+ concentrations – relaxed state of the muscle is enforced:
o Tropomyosin blocks the active myosin binding sites on actin molecule
o Myosin cross bridges cannot attach to the active binding sites on actin
● At higher intracellular Ca2+ concentrations:
o additional calcium binds to troponin [inactive troponin binds with two (2) Ca2+]
o Calcium-activated troponin binds an additional two Ca2+ at a separate regulatory site
o Calcium–activated troponin undergoes a conformational change
▪ The conformational change moves the tropomyosin away from active binding sites on actin
▪ Myosin head can now bind with the actin active binding sites & cycle
▪ This permits contraction (sliding of the thin filaments by the myosin cross bridges) to begin
MYOSIN FILAMENT: The Mechanism of Myosin Cross-Bridge Formation

(note: see fig.9.11. Marieb, 5th ed. or fig. 6.8 pp 193. Marieb 9th ed. Essentials of Human Anatomy & Physiology)
● Cross bridge formation – myosin cross-bridge attaches to the actin filament
● Working (power) stroke – is the “tilt” of the myosin head
o myosin head binds, snap or pivots, change from high-energy configuration to a bent, low-energy shape
& pulls actin filament toward M line (center of sarcomere)
o Hydrolysis of ATP  ADP + Pi (inorganic phosphate) released from myosin head
● Cross bridge detachment – ATP attaches to myosin head (low-energy configuration) & the cross bridge
detaches
● “Cocking” of the myosin head – energy from hydrolysis of ATP into ADP + Pi (ATPase) provides energy
to return or “cocks” the myosin head into the high-energy state
The “ACTIVATED” ACTIN FILAMENT & MYOSIN CROSS BRIDGES: “WALK-ALONG” / RATCHET Theory of
Contraction (note: please refer to fig. 6.7. pg. 77. Chapter 6. Guyton & Hall. Textbook of Medical Physiology. 11th ed.)
● Postulates that when a myosin head attaches to the actin active site cause changes in intramolecular
forces between the myosin head & the arm of the cross-bridge
● The new alignment of forces causes the myosin head to tilt toward the arm dragging the actin filament
along with it moving the actin filament towards the center of the sarcomere
● The “power stroke” – is tilt of the myosin head.
● The myosin head automatically breaks away from the active site
● The myosin head returns to a normal perpendicular position which combines again with a new active
site farther down on the actin filament.
● The myosin head tilts, new power stroke is created
● Actin filament moves another step forward towards the center of the sarcomere
● The myosin head cross-bridges bends back & forth and step-by-step walk along the actin filament,
pulling the ends of actin filament towards the center of the myosin filament.
● Each cross-bridges operate independently, attaching & pulling in a repeated, continuous cycle.
● The greater the number of cross bridges in contact with actin filament, the greater the force of
contraction.
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Sequence of Chemical Events in the Motion of the Myosin Heads
● The process (# 1-6) repeats again & again until actin filaments pull the Z membrane up against the ends of the
myosin filaments or until the load on the muscle becomes too great for further pulling to occur.
1. Before contraction begins, the heads of the cross-bridges bind with ATP
o ATPase enzyme activity of the myosin head cleaves the ATP, leaving ADP + Pi (phosphate ion), bound
to the myosin head.
o In this state, the conformation of the myosin head extends perpendicularly toward the actin filament
but is not yet attached to the actin.
2. Troponin-tropomyosin complex binds with calcium ions (when intracellular calcium ions are high)
o Actin active binding sites are exposed/uncovered
o Myosin head binds with the actin active binding sites
3. Binding of the head of the myosin cross-bridge with the actin active site causes a conformational
change in the myosin head
o The myosin head tilt toward the arm of the cross-bridge  creates a power stroke for pulling the actin
filament.
o The energy that activates the power stroke is the energy already stored, like a “cocked” spring, by the
conformational change that occurred in the head when the ATP molecule was cleaved earlier.
4. When the head of the myosin cross-bridge tilts  release of ADP + Pi (phosphate ion) from the myosin
head
o At the site of release of ADP, a new molecule of ATP binds
o Binding of new ATP, causes detachment of the myosin head from the actin filament
5. After the head has detached from the actin, the new molecule of ATP is cleaved to begin the next cycle,
leading to a new power stroke.
o The energy again “cocks” the myosin head back to its perpendicular condition, ready to begin the new
power stroke cycle.
6. When the cocked head (with its stored energy derived from the cleaved ATP) binds with a new active
site on the actin filament, it becomes un-cocked & once again provides a new power stroke.
ATP – Providing The Energy for Skeletal Muscle Contraction

Sources of Energy for Skeletal Muscle Contraction
MUSCLE METABOLISM: ATP – Energy for Contraction

● When a muscle contracts, work is performed and energy is required.
ATP – is the only energy source used directly to power muscle contraction
● hydrolysis of the bonds of the ATP molecules, releases the needed energy = ADP + Pi (has high-energy
phosphate bond)
ATP + H2O = ADP + Pi
● ATP is regenerated from the phosphorylation of ADP + Pi
● Energy from ATP hydrolysis is transferred to the contractile unit of the skeletal muscle
● Muscles has very limited storage supplies of ATP (4-6 seconds worth of ATP)
● ATP has to regenerated continuously for muscle contraction to occur
FENN Effect – the greater the amount of work performed by the muscle, the greater the amount of ATP that is
cleaved to form ADP during the contraction process.
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Role/Uses of ATP (fig. 6.10, pp.196. Marieb. Essentials of Human Anatomy & Physiology. 9 th ed)
● provides most of the energy for cross-bridge movement & detachment (“walk-along” mechanism)
● operations of the calcium pump in the SR
● pump sodium & potassium ions through the muscle fiber membrane to maintain appropriate ionic
environment for propagation of muscle fiber action potentials
Sources of ATP – Three (3) Pathways for ATP (re) generation:

[refer to Figure 6.10, p. 194 – 194. Elaine N. Marieb Essentials of Human A & P. 12th ed.]
1. Direct phosphorylation of ADP with creatine phosphate

2. Anaerobic glycolysis – Stored glycogen via anaerobic pathway with lactic acid formation
3. Aerobic respiration
Direct Phosphorylation of ADP by Creatine Phosphate:

● Creatine phosphate (CP) – high energy molecule stored in muscle fibers but not in other cell types
● As ATP is depleted, interactions between CP & ADP results in transfer of a high-energy phosphate
group from CP to ADP = ATP
● Regenerate ATP in times of high demand for ATP use (fraction of a second)
● Disadvantage: Although muscle fibers store perhaps 5X as much CP as ATP, the CP supplies
are also soon exhausted (< 15 seconds).
Anaerobic Glycolysis & Lactic Acid Formation:

● ATP is generated from glucose through catabolism of blood glucose or breakdown of glycogen in the
muscles
● Glycolysis pathway – initial steps of glucose breakdown without use of oxygen (anaerobic)
o occurs in the cytosol; “sugar splitting”
▪ Glucose  broken down to two (2) pyruvic acid molecules  energy released is captured & used to
form ATP (2 ATP/glucose)
▪ with enough oxygen  pyruvic acid enters the oxygen-requiring aerobic pathways (mitochondria),
reacts with oxygen to produce more ATP
▪ Pyruvic acid + O2  ATP
o In vigorous (intense) muscle contraction when muscle contractile activity reaches 70% of maximum:
▪ Bulging muscles compress blood vessels
▪ Blood flow, oxygen & glucose delivery is temporarily impaired – unable to meet the needs of the
working muscles
▪ Sluggish aerobic pathway cannot keep up with the demands for ATP
▪ Pyruvic acid  enters anerobic glycolysis  converted into lactic acid
● Lactic acid – end-product of anaerobic glycolysis (oxygen-deficit) instead of CO2 & O2
o Diffuses into the bloodstream
o Is picked up & used as fuel & energy source by the liver, kidneys, & heart
o Is converted back into pyruvic acid or glucose by the liver  brought back to the bloodstream for
muscle use (CORI Cycle)
● Yields: 5% ATP
● Produces ATP much faster (2.5x than aerobic glycolysis)
● Sustains energy for short-term vigorous exercise (30-60secs of strenuous muscle activity)
● Disadvantages:
16
o Huge amount of glucose is used to produce small amounts of ATP
o Lactic acid accumulates = muscle fatigue + muscle soreness
Sources of ATP: Aerobic Respiration – mitochondria

● Provides  95 per cent of all energy used by the muscles for sustained, long-term muscle contraction
o 95% ATP for muscle activity (at rest, light to moderate prolonged exercise)
● Oxygen– requiring metabolic pathways – oxidative phosphorylation
o O2 combined with end-products of glycolysis & with various other cellular foodstuffs  ATP
▪ Foodstuffs – carbohydrates, proteins, fats
● Oxidative phosphorylation – sequence of series of chemical reactions/O2-requiring metabolic pathways
in which the bonds of fuel molecules (glucose) are broken & energy released is used to make ATP
o Glucose + O2  CO2 + H2O + ATP

▪ Carbon dioxide diffuses out of muscle tissue into the blood & expelled out through the lungs
o Glucose sources:
▪ muscle glycogen (start of exercise)
▪ Blood glucose
▪ Pyruvic acid
▪ Free fatty acids
▪ Amino acids
● High yield = 36 ATP/glucose
● Disadvantages:
o Slow – many steps
o Oxygen-requiring – requires continuous delivery of oxygen & nutrient fuels to keep the muscle going.
Energy Used During Sports Activities

● ATP & CP stores – activities that requires surge of power (weight lifting, diving, sprinting)
● Anaerobic glycolysis – on-&-off burst activities (tennis, soccer, 100-m swim)
● Aerobic respiration – prolonged activities requiring endurance than power (marathon, jogging)
Anaerobic + Aerobic – pathways intertwined

● Aerobic threshold – length of time muscle can continue to contract using aerobic pathways
● Anaerobic threshold – point at which muscle metabolism converts to anaerobic glycolysis
MUSCLE FATIGUE & OXYGEN DEBT
Muscle Fatigue – the muscle is in a state of physiological inability to contract

● occurs when muscles are exercised strenuously for a long time
o A muscle is fatigued when it is unable to contract even though it is still being stimulated.
o Without rest, a working muscle begins to tire & contract weakly until it finally ceases reacting & stops
contracting.
● Results from inability of the contractile & metabolic processes of the muscle fibers to continue
supplying the same work output.
Muscle Fatigue: Factors / Causes – not fully known

● Depleted muscle glycogen – increases in almost direct proportion to the rate of depletion of muscle
glycogen
● Diminished transmission of nerve signals at the neuromuscular junction – intense, prolonged muscle
activity diminishes nerve signal transmission at neuromuscular junction  diminish muscle contraction
● Inadequate blood flow – interruption of blood flow in a contracting muscle causes loss of nutrient
supply (loss of oxygen)  lactic acid forms (anaerobic pathway)
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o Oxygen depletion – inability to take in oxygen fast enough to keep the muscles supplied with all the O2
needed when working vigorously
Muscle Fatigue – occurs when:

● ATP production fails to keep pace with ATP use  relative deficit of ATP  contractures/cramps
o Muscle glycogen reserves are depleted during increase demands
o ATP consumption overshadows ATP production = less muscle contraction efficient  muscle fatigue
▪ Contractures (cramps) – state of continuous contraction when ATP are not available to detach the
myosin cross-bridges from the thin actin filaments
● Lactic acid accumulates in the muscle – when muscles lack enough oxygen for aerobic respiration
o Excessive lactic acid accumulation (anerobic pathway) = drop in blood pH  aching muscles  muscle
fatigue
▪ “burning sensation” is felt if lactic acid accumulation is taking place.
● Ionic imbalances are present (Na+-K+ pump) – inadequate supply of ATP
o Adequate ATP – functional pump
o Inadequate ATP – non-responsive muscles
o AP transmitted = loss of K+ from muscle cells & excess of Na+ influx into muscle cells
▪ Intense exercise produces rapid muscle fatigue (with rapid recovery)
● Na+-K+ pumps cannot restore ionic balances quickly enough
▪ Low-intensity exercise produces slow-developing fatigue
● SR is damaged and Ca2+ regulation is disrupted
Oxygen Debt / Oxygen Deficit

● Vigorous exercise causes dramatic changes in muscle chemistry
● for a muscle to return to a resting state after an activity:
o Oxygen reserves must be replenished
o Accumulated lactic acid must be re-converted to pyruvic acid
o Glycogen stores must be replaced
o ATP & CP reserves must be re-synthesized
o Liver must convert persisting lactic acid released into the blood during muscle activity to glucose or
glycogen
● During the recovery period after activity:
o the individual breathes rapidly & deeply – continues until the muscles have received the amount of
oxygen needed to get rid of the accumulated lactic acid & replenish ATP & creatine phosphate reserves.
● Extra amount of oxygen that must be taken in by the body for the restoration of all O2-requiring
processes
● Represents the difference between the amount of O2 needed for totally aerobic muscle activity and
the amount actually used.
● Amount of oxygen used during exercise depends on:
o Age
o Size
o Athletic training
o Health
● The more exercise the person is used to, the higher is the oxygen use (and aerobic threshold) during
exercise, and the lower oxygen debt
Heat Production during Muscle Activity

● Only 40% of the energy released in muscle activity is useful as work
● remaining 60% is given off as heat
● Dangerous heat levels are prevented by radiation of heat from the skin & sweating
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● Shivering represents muscle contractions to produce more heat
19
Excitation of Skeletal Muscle
Neuromuscular Transmission & Excitation-Contraction Coupling
[REFER to: fig.6.4 / 6.5. p.188 – 190. Elaine N. Marieb. Essentials of Human A&P. 12th ed.]
Regulation of Contraction
● Skeletal muscle fiber contracts when stimulated by a nerve ending & propagate an electric current or
action potential
● AP causes increase in intracellular calcium ion levels  muscle contraction
● Excitation–contraction coupling – series of events linking the electrical signal to muscle contraction
Motor Unit – consists of one neuron & all the skeletal muscle fibers it stimulates
● One motor neuron (nerve cell) may stimulate a few muscle fibers or hundreds of them, depending on
the particular muscle & the work it does
Motor End Plate – a complex formed by branching ends of large, myelinated nerve fiber terminals (axon
terminals) that invaginate (junctional folds) into the surface of the muscle fiber just outside the sarcolemma
● Covered by Schwann cells to insulate it from surrounding fluids
Axon – long threadlike extension of the neuron

● upon reaching the muscle, branches into a number of axon terminals, each forming a junction with the
sarcolemma of a different muscle cell
The NEUROMUSCULAR JUNCTION – a junction formed between the nerve axon terminals with the sarcolemma
of a muscle cell; “nerve-muscle” junction
● Each axonal branch (nerve ending) forms a neuromuscular junction with a single muscle fiber
● Each muscle fiber has one neuromuscular junction
● Skeletal muscle fibers are innervated by large, myelinated nerve fibers
● Skeletal muscles are stimulated by motor neurons of the somatic (voluntary) nervous system
● Axons of these neurons travel in nerves to muscle cells
● Axons of motor neurons branch profusely as they enter the muscle
Physiologic Anatomy of the Neuromuscular Junction

● Synaptic gutter or synaptic trough – invaginated membrane of the muscle fiber
● Synaptic space or cleft – space between the axon terminals & the muscle fiber membranes
o Filled with glycoprotein-rich gel-like extracellular substance of interstitial fluid
o contains acetylcholinesterase (AChE) – enzyme capable of destroying acetylcholine
● Subneural clefts (junctional folds) – numerous folds of the muscle membrane/ sarcolemma at the
bottom of the gutter
o increases the surface area at which neurotransmitter can act
o contains ACh receptors (acetylcholine-gated ion channels)
● Nerve axon terminals – nerve ending which contains numerous mitochondria that supply ATP
o ATP – source of energy for synthesis of excitatory neurotransmitter acetylcholine
● Synaptic vesicles – numerous, small membranous sacs contained within the axon terminals
o Absorbs & stores acetylcholine
o Releases ACh into synaptic cleft via exocytosis
● ACETYLCHOLINE (ACh) – a neurotransmitter synthesized in the cytoplasm of the axon terminals
Secretion & Release of Acetylcholine:

● When a nerve impulse reaches the end of an axon at the neuromuscular junction:
o Voltage-regulated calcium channels open  allows Ca2+ to diffuse into the axon from ECF
o Ca2+ entry into the axon terminal causes axonal synaptic vesicles (contains ACh) to fuse with the axonal
membrane
o ACh are released from synaptic vesicles into the synaptic cleft via exocytosis
o ACh diffuses across the synaptic cleft to ACh-receptors on the sarcolemma along the subneural folds
o Binding of ACh to its protein receptors on the sarcolemma initiates an action potential in the muscle
o ACh binds to its ACh receptors at the motor end plate
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o Binding opens chemically (ligand)-gated channels (ACh-gated ion channel) on the sarcolemma
Acetylcholine-Receptor Channel (refer to figure below)

A. Closed state.
B. After acetylcholine (ACh) has been attached & binds to its ACh-receptors on the sarcolemma & a
conformational change has opened the chemically-gated channel  Na+ ions enter the muscle fiber & excite
contraction
● ACh-gated receptor channel – are large protein complex tubular channels
o Remains constricted [Closed state] until ACh binds with it [Open state]
o Once opened, allows passage of positively-charged ions: Na+, K+ & Ca2+
o Note: the strong negative charges at the protein channel mouth repels & prevents the entry of
negatively-charged ions (chloride ions) from the ECF into the ICF
▪ Negative ions (chloride ions) do not pass through the ACh-protein receptor channels.
Role of Acetylcholine (ACh)

● Binding of acetylcholine to the protein receptor channels on the sarcolemma
● If enough acetylcholine is released, the sarcolemma at that point becomes temporarily even more
permeable to sodium ions (Na+), which rush into the muscle fiber, & to potassium ions (K+), which diffuse out
of the muscle fiber.
o More Na+ enters than K+ leaving the muscle cell.
▪ Very negative potential on the inside of the muscle membrane (–80 to –90 mv)
● Pulls (more) positively charged Na+ into the inside of the fiber
● Prevents efflux of the positively-charged K+ ions when they attempt to pass outward
● Ionic imbalance gives the cell interior an excess of positive ions, which reverses the resting electrical
conditions of the sarcolemma  depolarization
● Depolarization, opens more channels that only allow Na+ entry  more Na+ diffuses through the
channel into the muscle
o Na+ ions diffuses into the cell  interior of the sarcolemma becomes less negative (local positive
potential change)  end plate potential  initiates an action potential that spreads along the muscle
membrane  muscle contraction
Destruction of Acetylcholine
● ACh released into the synaptic cleft continues to activate ACh-protein receptor channels on the
sarcolemma.
● Two ways:
o Acetylcholinesterase enzyme (AChE)
o ACh in small amounts diffuses out of the synaptic cleft & no longer available to act on the sarcolemma
● Acetylcholinesterase (AChE) – enzyme which destroys quickly released ACh (after its use)
o Present in the sarcolemma & synaptic cleft
o ACh broken down into acetic acid & choline
● Single nerve impulse produces only one contraction
● ACh destruction prevents continued muscle fiber contraction in the absence of additional stimuli
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The Neuromuscular Transmission of Nerve Impulse
The Generation & Propagation of the Action Potential across the Sarcolemma
● A nerve impulse travels along a motor nerve to its nerve branch endings
● A single nerve impulse produces only one muscle contraction
● When the nerve impulse reaches the end of an axon at the neuromuscular junction:
o Voltage-regulated calcium channels on the axonal membrane opens & allows Ca2+ to enter the axon
from the ECF
o Once inside the axon terminal, Ca2+ causes the axonal synaptic vesicles containing ACh to fuse with the
axonal membrane
o The fusion causes the axonal synaptic vesicles to release the neurotransmitter acetylcholine (ACh) into
the synaptic cleft via exocytosis
● ACh diffuses across the synaptic cleft & attaches to ACh-membrane protein receptors on the
sarcolemma
● ACh acts on a local area of the sarcolemma to open multiple ACh-gated ion channels
● Opening of ACh-gated ion channels cause a patch of the sarcolemma to temporarily become more
permeable to sodium ions (Na+)
● Sodium ions (Na+) rush into the muscle cell & potassium (K+) ions diffuse out of the cell
● With more Na+ ions entering the cell from the ECF than the K+ ions leaving the cell, gives the interior of
the cell an excess of positive ions, which reverses the electrical conditions of the sarcolemma, opening more
sodium protein-gated channels that only allows Na+ entry into the cell
● The “upset” generates & initiates an electrical current or action potential locally on an area (patch) of
the sarcolemma
● The resting membrane potential is decreased & depolarization occurs
● If the nerve impulse (stimulus) is strong enough, an action potential is initiated
o “All-or-none” principle: once generated, the action potential is unstoppable & travels over the entire
surface of the sarcolemma, conducting electrical impulse from one end of the cell to the other.
● The action potential depolarizes the sarcolemma & travels deep within the muscle fiber through the
T-tubules & causes the release of calcium ions from the sarcoplasmic reticulum into the sarcoplasm
● Increase intracellular calcium ions  muscle contraction occurs.
Muscle Action Potential

● Initiation & conduction of action potentials in the nerve fiber are the same with skeletal muscle fiber
● Quantitative differences exist:
o Resting membrane potential – about –80 to –90 mv in skeletal fibers – same as in large myelinated
nerve fibers
o Duration of action potential – 1 to 5 ms in skeletal muscle – 5X longer as in large myelinated nerves
o Velocity of conduction – 3 to 5 m/sec – 1/13 the velocity of conduction in the large myelinated nerve
fibers that excite skeletal muscle
Generation of MUSCLE Action Potential

● Resting sarcolemma is polarized
● ACh binds to ACh receptors on the sarcolemma opens chemical gated-Na+ channels within the ACh
receptors
● Transient permeability changes occur in the sarcolemma that leads to a depolarization event that
includes reversal of polarity in a sarcolemma & propagation of an action potential along the membrane
Three Phases of an Action Potential across Sarcolemma
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● Resting Membrane Potential
● Depolarization  Propagation of AP
● Repolarization
● Resting Membrane Potential
Depolarization & Propagation of an Action Potential across Sarcolemma

● Nerve impulses depolarize a patch of the sarcolemma; neurotransmitter ACh attaches to membrane
protein receptors on the sarcolemma
o Na+ membrane protein channels open, Na+ enters the cell
● Propagation of an AP as a local depolarization wave  spreads to adjacent areas of the sarcolemma 
opens more voltage-regulated Na+ membrane protein channels  more Na+ ions diffuse into the cell along their
electrochemical gradient
Repolarization across Sarcolemma

● Repolarization restores the sarcolemma into its resting polarized state – closing of Na+ membrane
protein channels & opening of K+ membrane protein channels  K+ diffuses out of the muscle fiber along its
concentration gradient
● During repolarization, muscle fiber is in a refractory period in which the muscle cell cannot be
stimulated again until repolarization is completed.
● Repolarization only restores electrical conditions of the resting (polarized) state
o ATP-dependent sodium-potassium pump restores / re-establish ionic component of the resting state
Summary of Events in the Generation & Propagation of an Action Potential in Skeletal Muscle
● Electrical condition of a resting (polarized) sarcolemma – Sarcolemma impermeable to both ions
o The outside surface is positive & the inside surface is negative
▪ Na+ – predominant in ECF / K+ – predominant in ICF
● Depolarization & propagation of the action potential
o Production of end-plate potential at the motor-end plate causes adjacent areas of the sarcolemma to
become permeable to Na+ (Na+ voltage-gated protein channels opens)
▪ An axonal terminal of a motor neuron releases ACh into synaptic cleft at the neuromuscular junction
producing end-plate potential
o Na+ ions diffuses into the cell; the resting membrane potential is decreased (depolarization occurs)
o If stimulus is strong enough, an action potential is initiated
● Propagation of the Action Potential
o The positive charge inside the initial patch of sarcolemma changes permeability of an adjacent patch
opening more Na+ voltage-gated membrane protein channels in that area
o As a result, membrane potential in that area decreases  depolarization occurs  action potential is
initiated & propagated deep down into the inside of the skeletal muscle through T-tubules & travels along the
entire sarcolemma
● Repolarization
o Immediately after depolarization wave passes, the permeability of the sarcolemma changes:
▪ Na+ voltage-gated membrane protein channels close
▪ K+ voltage-gated membrane protein channels opens  K+ diffuses out of the cell  restores the
electrical condition of the resting (polarized) membrane
o Occurs in the same direction as depolarization
o Must occur before the muscle fiber can be stimulated again
Excitation – Contraction Coupling

Transverse Tubules – Sarcoplasmic Reticulum System
Role of Calcium ions
T Tubules – SR System
● T tubules – allows transmission of action potentials deep within the muscle fiber from the sarcolemma
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● Travel of AP along T tubules causes release of CALCIUM ions from the sarcoplasmic reticulum into the
sarcoplasm
o Calcium ions – causes muscle contraction by excitation-contraction coupling
● Transverse tubules (T tubules) – internal extensions of sarcolemma
o Small, interlacing branching tubules
o Begins at the sarcolemma & runs transversely across myofibrils; penetrates deeply into muscle fibers
from one side to the other
● SR – two parts:
o Terminal cisternae – large chambers; abuts T tubules
o Longitudinal tubules – surrounds surfaces of contracting myofibrils
EXCITATION – CONTRACTION Coupling in Skeletal Muscles
(note: see fig.9.11. Marieb, 5th ed. or fig. 6.8 pp 193. Marieb 9th ed. Essentials of Human Anatomy & Physiology)
● Sequence of events by which transmission of an action potential along the sarcolemma leads to the
sliding of myofilaments
● Increase in intracellular calcium ion concentration cause the sliding of the filaments
STEPS in Excitation – Contraction Coupling in Skeletal Muscle Contraction

● Once generated, the action potential:
o Is propagated along the sarcolemma
o Travels down the T tubules
o Passes the triad regions & triggers the release of Ca2+ from the terminal cisternae of the SR into the
sarcoplasm which makes Ca2+ available to the myofilaments
● Release of Ca2+ from SR:
o “double zippers “at the T tubules–SR junctions play into action
o Protein particles on the sides of the T tubules are sensitive to changes in voltage & change
conformation (3D-shape) in response to an action potential
o Voltage-regulated change is carried to the SR foot, which undergoes shape changes & opens its
calcium channel
● Ca2+ binds to troponin C, removes the blocking action of tropomyosin on the actin active binding sites
o Actin active binding sites exposed
● Myosin cross-bridge formation occurs, alternately attach & detach
o Thin filaments are pulled toward the center of the sarcomere
o Hydrolysis of ATP into ADP & Pi (inorganic phosphate) powers the cycling process between actin &
myosin filaments
● Short-lived Ca2+ signals ends & AP is over
o Hydrolysis of ATP into ADP & Pi (inorganic phosphate) also removes the Ca2+ back to the SR for storage
● Low Ca2+ levels, tropomyosin blockade on actin active binding site is restored; myosin ATPases activity
are inhibited
o Cross-bridges activity ends & the muscle fiber relaxes
Neuromuscular Transmission & Excitation-Contraction Coupling
24
Table 9.2.: Roles of Ionic Calcium in Muscle Contraction
(pp. 292. Elaine N. Marieb. Human Anatomy & Physiology. 5th ed.)
Role Mechanism
As the nerve impulse reaches the axon terminal, the voltage-regulated calcium gates
Promotes neurotransmitter open allowing calcium ions to enter the terminal, which triggers fusion of the
release synaptic vesicles with the axonal membrane & causes exocytosis of the
neurotransmitter acetylcholine into the synaptic cleft
When an AP is transmitted along the T tubules of skeletal muscle fibers, voltage

sensors (integral proteins in the T tubule wall) responds by communicating with
Triggers calcium release
adjoining SR foot proteins that regulate calcium channels in the SR membrane. As a
from the SR
result, calcium is released from the SR, causing a local rise in calcium ion
concentration in the sarcoplasm
(1) When calcium binds to troponin in skeletal & cardiac muscles, structural changes
occur in troponin that expose active binding sites on actin. As a result, myosin cross-
Triggers sliding of bridge binding can occur & ATPases on myosin head are activated
myofilaments & ATPase
activity (2) When calcium binds to calmodulin (an intracellular calcium-binding protein) in
smooth muscles, a kinase enzyme is activated that catalyzes phosphorylation of
myosin. As a result, myosin cross-bridges are activated & sliding begins
Promotes glycogen When calcium binds to & activates calmodulin, the activated calmodulin mobilizes a
breakdown & kinase enzyme that initiates the breakdown of glycogen to glucose. The muscle fiber
ATP synthesis then metabolizes glucose to produce ATP for muscular work
CHARACTERISTICS OF WHOLE SKELETAL MUSCLE CONTRACTION

Functional Types of Muscle Fibers: Fast vs. Slow Muscle Fibers
Types of Muscle Contraction: Isometric vs. Isotonic Contraction
[refer to: fig.6.9. pg. 193. Chap.6. Muscle Physiology. E.N. Marieb Essentials of Human A&P 12th ed.]
25
Contraction of Skeletal Muscle Fibers
● Contraction – refers to the activation of myosin’s cross bridges (force-generating sites)
o Shortening occurs when the tension generated by the cross bridge exceeds forces opposing shortening
o Contraction ends when cross-bridges become inactive, the tension generated declines, & relaxation is
induced
● In skeletal muscles, the “all-or-none” law of muscle physiology applies to the muscle fiber, not to the
whole muscle.
o It states that a muscle fiber will contract to its fullest extent when it is stimulated adequately; it never
partially contracts.
● Whole muscle contracts & reacts with graded responses, or different degrees of shortening, which
generate different amounts of force
o GRADED MUSCLE Contraction can be produced in two (2) ways:
▪ (1) Frequency Summation – by changing (increasing) the frequency of muscle stimulation
● can lead to tetanization
▪ (2) Multiple Fiber Summation – by changing (increasing) the number of muscle fibers / motor units
being stimulated at one time.
● Muscle twitches – is a response of a muscle to a single & brief threshold stimulus
o single, brief, jerky muscle contractions (should not normally occur)
o sometimes result from certain nervous system problems
o Elicited by instantaneous electrical excitation of the nerve to a muscle or by passing a short electrical
stimulus through the muscle itself
● Summation – adding together of individual twitch contractions to increase the intensity of overall
muscle contraction
Muscle Response to INCREASINGLY RAPID STIMULATION – Frequency Summation

● At low frequency of stimulation, individual muscle contraction occurs one after another
● As frequency increases, each new contraction occurs before the preceding one is over
o In most types of muscle activity, nerve impulses are delivered to the muscle at a very rapid rate—so
rapid that the muscle does not get a chance to relax completely between stimuli.
Frequency Summation – results as the effects of the successive contractions are “summed” (added) together,
& the contractions of the muscle get stronger & smoother.
● The second contraction is added partially to the first, so that the total strength of contraction rises
progressively with increasing frequency
● Frequently delivered stimuli (muscle does not have time to completely relax) increases contractile force
● Tetanization – Results when frequency reaches a critical level, successive contractions occurs rapidly
until they fuse together
o Whole muscle contraction appears to be completely smooth & continuous
o Second contraction occurs before muscle completely relaxes
▪ In a partially contracted muscle, more Ca2+ is being released by the SR to replace those taken up back
to SR, even in between AP  tension  shortening  full contractile force maintained (without relaxation in
between)
o Contractions are summed (added)
o At a slightly higher frequency, the strength of contraction reaches its maximum  any additional
increase in frequency beyond that point has no further effect in increasing contractile force
▪ Threshold stimulus – the stimulus strength at which the first observable muscle contraction occurs
● Beyond threshold, muscle contracts more vigorously as stimulus strength is increased
● Maximal stimulus is the strongest stimulus that produces increased contractile force where all
muscle’s motor unit are recruited
o Increasing stimulus intensity beyond maximal stimulus does not produce stronger contraction
● Unfused or incomplete tetanus – results from constant strength or voltage, the faster rate of
stimulation & more rapidly delivered stimuli
● Fused or complete tetanus / Tetanic contractions – results if stimuli are given quickly enough, with no
26
evidence of relaxation seen, & the contractions are completely smooth & sustained
o Tetanic contraction is normal & desirable.
Muscle Response to STRONGER STIMULI – Multiple Fiber Summation

● Tetanus produces stronger (more forceful) muscle contractions, but its primary role is to produce
smooth and prolonged muscle contractions.
● Force of muscle contraction depends on how many of its cells are stimulated.
o few cells are stimulated, muscle as a whole contract only slightly
o all motor units are active & all the muscle fibers are stimulated, stronger force of muscle contraction
● Size principle
o Weak signal comes from CNS to contract a muscle  stimulates smaller motor units (vs. larger motor
units)
▪ Smaller motor units with small motor nerve fibers (small motor neurons in the SC are more excitable
vs. large ones)
o Increase strength of signal  larger & larger motor units begin to be excited.
o Force of large motor units 50X > than smaller motor units
o Importance:
▪ allows gradations of muscle force during weak contraction in small steps; the steps become
progressively greater when large amounts of force are required
▪ different motor units are asynchronously driven by the spinal cord; alternate contractions among motor
units occurs one after the other  provides smooth contraction even at low frequencies of nerve signals
Treppe – The Staircase Effect

● A state wherein the strength of muscle contraction reaches a plateau when a muscle begins to
contract after a long period of rest, its initial strength of contraction may be ½ its strength after 10-50 muscle
twitches
● Caused by increasing availability of Ca2+ in the sarcoplasm from SR with successive muscle AP & failure
of the SR to recapture the Ca2+ immediately
Force of Muscle Contraction – is affected by:

● Number of muscle fibers contracting – the more motor fibers in a muscle, the stronger the contraction
● Relative size of the muscle – the bulkier the muscle, the greater tension, greater its strength
● Series-elastic elements
● Degree of muscle stretch – muscles contract strongest when muscle fibers are 80-120% of their normal
resting length
Series-Elastic Elements – Non-contractile structures of muscles with ability to stretch & recoil
o Other movable structures
o Connective tissue coverings & tendons
● Forces brought about by:
o Internal tension – generated by contractile elements (myofibrils) stretches the series-elastic elements
o External tension – force is transferred to the load which causes recoil and return of muscle to normal
resting length
Velocity & Duration of Contraction

● Muscles vary how fast they can contract & how long they can continue to contract before they fatigue
● Influenced by:
o Type of muscle fiber (fast/slow muscle fibers)
o Load – muscles attached to bones (resistance)
▪ Contracts faster when no load is added
▪ The greater the load, the longer the latent period, the slower the contraction, the shorter the duration
of contraction
o Recruitment
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▪ The more motor units that are contracting, the more prolonged the contraction can be
Motor Unit: nerve-muscle functional unit

● A single motor neuron (nerve fiber) & all the muscle fibers it supplies
● The number of muscle fibers per motor unit can vary from four to several hundred
● Muscles that control fine movements have smaller motor units (nerve fibers > muscle fibers)
o fingers, eyes
o 1:1 nerve to fiber
● Large weight-bearing muscles have large motor units
o thighs, hips, leg
o 1:2000 (nerve to fiber
● Muscle fibers from a motor unit are spread throughout the muscle
● Contraction of a single motor unit causes weak contraction of the entire muscle
Functional Types of Muscle Fibers: FAST vs. SLOW MUSCLE FIBERS
Functional Types of Muscle Fibers

● Based on speed of contraction (determined by speed in which ATPases split ATP):
o SLOW muscle fibers o FAST muscle fibers
● Based on the major ATP-forming pathways:
o Oxidative fibers – uses aerobic pathways
o Glycolytic fibers – uses anaerobic pathways
● These two criteria define three categories:
o slow oxidative fibers o fast glycolytic fibers
o fast oxidative fibers
Speed of Contraction
● SLOW OXIDATIVE fibers
o contract slowly o fatigue resistant
o have slow acting myosin ATPases
● FAST GLYCOLYTIC fibers
o contract quickly o are easily fatigue
o have fast myosin ATPases
● FAST OXIDATIVE fibers
o contract quickly o have moderate resistance to fatigue
o have fast myosin ATPases,
FAST vs. SLOW Muscle Fibers – Every muscle in the body is a mixture of the two types of muscle fibers:
● FAST Muscle Fibers (white muscle) – Large fibers for greater strength
o Extensive SR for rapid release of calcium ions to initiate contraction
o Large amounts of glycolytic enzymes for rapid release of energy by the glycolytic process
o Less extensive blood supply because oxidative metabolism is secondary
o Fewer mitochondria
o react rapidly and are adapted for rapid powerful muscle contractions
▪ Jumping / Short-distance powerful running
● SLOW Muscle Fibers (red muscle) – Small fibers
o Innervated by smaller nerve fibers
o More extensive blood vessel system & capillaries to supply extra amounts of oxygen
o Increased numbers of mitochondria to support high levels of oxidative metabolism
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o Fibers contain large amounts of myoglobin
▪ Myoglobin – iron-containing protein in muscles
● Combines with oxygen & stores it until needed
● Speeds up oxygen transport to the mitochondria
● gives slow muscles reddish appearance
o react slowly but with prolonged contraction
o are adapted for prolonged, continued muscle activity
▪ Support of the body against gravity
▪ Long-continuing athletic events (marathon)
Skeletal Muscle Tone – Results from different motor units scattered through the muscle & receives low rate of
nerve impulses from the spinal cord
● a state of continuous partial muscle contractions
● NOT consciously controlled.
● when a muscle is voluntarily relaxed, some of its fibers are contracting— first one group & then
another
● contractions are not visible
● Spinal reflexes account for muscle tone by:
o Activating one motor unit & then another in a systematic manner
o Responding to activation of stretch receptors in muscles and tendons
● Is the constant, slightly contracted state of all muscles at rest, which does not produce active / visible
movements
● Keeps the muscles firm, healthy, & ready to respond to stimulus
● Stabilize joints & maintain posture
Types of Skeletal Muscle Contraction: Isometric / Isotonic Contractions

● muscle contracts, they shorten.
● BUT not all muscle that contracts always shorten.
● TENSION (FORCE) – common to all muscle contractions
o develops in muscle as the actin & myosin myofilaments interact & the myosin cross-bridges attempt to
slide the thin actin-containing myofilaments past the thick myofilaments.
ISOTONIC Contractions – “same tone”

● Muscle changes in length (decreasing the angle of the joint)  force moves the load
● Decreasing muscle length
● Muscle shortens during contraction
● Tension on the muscle remains constant
● the myofilaments are successful in their sliding movements  muscle shortens  movement occurs
o Thin filaments slide past the thick ones
● Characteristics of isotonic contraction depend on the load against which the muscle contracts & the
inertia of the load.
● Examples:
o Bending the knee
o lifting weights
o smiling
● Types of Isotonic Contractions
29
o Concentric contractions – the muscle shortens & does work
o Eccentric contractions – the muscle contracts as it lengthens
o Coordination & purposeful movements
▪ Arm rotation
▪ Smiling 
▪ SQUATS (deep knee bends) – knees flex, quadriceps muscles of the anterior thigh lengthen (stretched)
but also contract (eccentric) at the same time to counteract the force of gravity & control descent of the torso
(“muscle braking”) to prevent joint injury
● Raising the body back to its starting position requires the same muscles (quadriceps) contract
concentrically as they shorten to extend the knees again
ISOMETRIC Contractions – “same measurement” or length

● Increasing muscle tension
● Muscle does not shorten during contraction
● Tension increases to the muscle’s capacity, but the muscle neither shortens nor lengthens
● Contractions in which the muscles do not shorten
● Thick myosin filaments are “spinning their wheels” & the tension in the muscle keeps increasing
o The cross-bridges are generating force but are not moving the thin filaments
o They are trying to slide, but the muscle is pitted against some more or less immovable object.
● Occurs if the load is greater than the tension the muscle is able to develop
● Records strictly changes in force of muscle contraction itself
● Duration of contractions adapted to individual muscle functions
● Examples:
o Ocular muscles – contracts rapidly to maintain eye fixation on objects for visual accuracy
o Soleus muscles – slow contraction for continual, long-term body support vs. gravity
o Gastrocnemius muscles – contracts moderately rapidly to provide sufficient velocity of limb movement
(running/jumping)
o when you push the palms of your hands together in front of you, your arms & chest muscles are
contracting isometrically.
Effects of Exercise on Muscles
Adaptations to Exercise (“use it or lose it!”)

● The amount of work a muscle does changes the muscle.
o Muscles used actively or strenuously increase in size or strength, become more efficient & fatigue
resistant
o Inactive muscles lead to muscle weakness & wasting
▪ Muscle inactivity (due to a loss of nerve supply, immobilization, or whatever the cause) always leads to
muscle weakness & wasting.
● Regular exercise increases muscle size, strength, & endurance.
Adaptations to Aerobic Exercise (Endurance Exercises)

● results in changes in skeletal muscles
o Jogging/Biking/Swimming/Fast walking
● Efficient muscle metabolism, greater muscle endurance & strength & resistance to fatigue
● Due to:
30
o Capillaries around muscle fibers increase in number – increase blood supply to muscles
o Increase mitochondria in individual muscle cells
o Store more O2 by increasing myoglobin synthesis
● Aerobic exercise helps reach a steady rate of ATP production & improves the efficiency of aerobic
respiration.
● Benefits:
o Overall body metabolism improves & neuromuscular coordination becomes more efficient
o Improved GIT motility & elimination
o Enhances strength of the skeletal system
o Cardiovascular changes: hypertrophy of heart muscles, increases stroke volume (more blood
pumped out/beat)
o Circulatory changes: release of fatty deposits from blood vessel walls
o Respiratory system: more efficient gas exchange in the lungs & improve delivery of oxygen (and
nutrients) to all body tissues
Adaptations to Anaerobic Exercise [Resistance Exercise]

● muscles are pitted against high-resistance or immovable forces (isometric exercise)
● muscles are forced to contract with much force as possible
● Muscle hypertrophy occurs from sustained muscle activity (resistance exercise)
o Resistance exercises require very little time & little or no special equipment.
o A few minutes every other day is usually sufficient.
● Increase in bulk of muscles is due to increase in size & enlargement of individual muscle cells which
makes more contractile filaments than increase in number of muscle cells
o amount of connective tissue that reinforces the muscles also increases
● Due to:
o More mitochondria
o Forms more myofilaments & myofibrils
o Stores more glycogen
o Increase connective tissue between cells
o Increase muscle strength & size
31
MUSCLE PHYSIOLOGY: SMOOTH MUSCLE
Physical Structure & Function: visceral, non-striated, involuntary

● Non – striated
● Involuntary
● Small, spindle-shaped fibers
● 2 – 10m diameter; several hundred m length
● Each smooth muscle cell has a single nucleus.
● Lack the coarse connective tissue sheaths of skeletal muscle, but have fine endomysium
● Essentially have the same contractile mechanisms as skeletal muscle
● Slow, sustained contraction
● Found in the walls of hollow (tube-like) visceral organs: Stomach / urinary bladder / respiratory
passages / walls of blood vessels
o Except: HEART – cardiac muscle
Smooth Muscle Fibers

● Organized into two layers of closely apposed fibers – contraction alternately constricts (making cavity
smaller / bigger (enlarge/dilates/opens):
o Outer longitudinal layer – muscle fibers run parallel to the long axis of the organ
▪ Contraction of the organ, muscle layer dilates & shortens
o Inner circular layer – muscle fibers run around the circumference of the organ
▪ Contraction of this layer constricts the lumen (cavity) of the organ & the organ elongates.
● Contraction changes the shape of the organ & generates force to mix substances & move/propel food
& other substances through specific pathways along the internal body channels
● Peristalsis – “around contraction”
o alternating contraction and relaxation of the two opposing layers mixes substances in the lumen &
squeezes them through the lumen of the hollow organs
o wavelike motion that keeps food moving through the small intestine
Physiologic Anatomy of the Neuromuscular Junction in Smooth Muscles

● Absent neuromuscular junctions
o Diffuse junctions/contact junctions – junction with a wide synaptic cleft between axonal innervations
of nerve fiber from autonomic nervous system & smooth muscle fiber cell membrane
o Varicosities – bulbous swellings at axonal nerve endings that branch diffusely on top of the sheet of
smooth muscle fibers
▪ Contains vesicles with neurotransmitter (acetylcholine & norepinephrine)
● Not secreted by the same nerve
▪ Absent Schwann cells – allow diffusion of neurotransmitter substance through the walls
o Contact junctions – in multi-unit smooth muscles
▪ Same as synaptic cleft in skeletal muscle neuromuscular junction
▪ A narrow space separating varicosity from the muscle cell membrane
▪ More rapid contraction vs. with diffuse junctions
● Nerve fibers (ANS) branch diffusely & only innervates the outer layer (top sheet) of smooth muscle
fibers
● Nerve fibers do not make direct contact with the smooth muscle fiber cell membranes
● Muscle excitation travels into the inner layer by action potentials or diffusion of transmitter
substances
32
● Axons that innervate smooth muscle fibers do not have typical branching end feet of the type in the
motor end plate on skeletal muscle fibers
Intracellular Organization in Smooth Muscles

● Less developed sarcoplasmic reticulum
o Tubular structures near sarcolemma
● Absent T tubules
● Caveoli – multiple, pouch-like infoldings in the sarcolemma that abuts the SR
o Allows sequestration of high concentration of Ca2+ from ECF
Organization of Myofilaments in Smooth Muscles

● Lacks a specific pattern relative to myofilaments
● Longer thick filaments
● Different proportion & organization of myofilaments
● Absent striations
● Absent sarcomeres
Proportion and Organization of Myofilaments in Smooth Muscles

● Lower ratio of thick to thin actin filaments (1:13)
● Actin-gripping heads found along the entire length of thick filaments
● Tropomyosin associated with thin filaments
● Absent troponin complex
● Thick & thin filaments arranged “on the bias” (diagonal/spiral down the long axis)
● Contain longitudinal bundles of non-contractile intermediate filaments attached to dense bodies
● Dense bodies – attached to sarcolemma
o act as anchoring points for thin filaments (like Z discs)
o intracellular cytoskeleton that harnesses the pull of the sliding myofilaments during a contraction
● Intermediate filaments – non-contractile filaments resist tension
Smooth Muscle Contraction: Excitation-Contraction Coupling
Contractile Mechanism of Smooth Muscle

● Major differences exist:
o Physical organization of smooth muscle
o Excitation-contraction coupling
o Control of contractile process by calcium ions
o Duration of contraction
o Amount of energy required for the contractile process
● Chemical Basis for Smooth Muscle Contraction
● Physical Basis for Smooth Muscle Contraction
● Electrical Basis for Smooth Muscle Contraction
● Characteristics of Smooth Muscle Contraction
Chemical Basis for Smooth Muscle Contraction

● Contains both actin & myosin filaments
● Absent troponin complex in the actin filament
● Actin & myosin interact according to the sliding filament mechanism
● Contractile process is activated by intracellular calcium ions
● ATP is also degraded to ADP+Pi to provide energy for contraction
33
Physical Basis for Smooth Muscle Contraction
● Contractile fibers are not arranged in sarcomeres
● Longer actin and myosin filaments
● Actin and myosin filaments are not arranged in striations
o Arranged in long bundles that extend diagonally around the cell periphery, forming a lattice around
the central nucleus
● Actin filaments are attached to dense bodies at regular intervals
● Dense bodies analogous to Z discs
● Ratio of thick to thin filaments is much lower than in skeletal muscle
● Contractile Unit – similar to contractile unit of skeletal muscle without the regularity of the contractile
unit of the skeletal muscle
o Large numbers of actin filaments radiate from two dense bodies
o the ends of actin filaments overlap a myosin filament midway between the dense bodies
o Dense bodies – same role as Z disc
● Myosin filament is a different isoform
o Slower Myosin ATPase activity
▪ Decreased rate of cross-bridge cycling and lengthening the contraction phase
o Myosin light chains – regulatory protein in the myosin head which controls contraction and relaxation
▪ Portion in the heads of the light chains of the myosin head in which myosin light chain kinase enzyme
can bind with to activate it
o Myosin filaments are bundled between the long actin filaments
o Entire surface is covered by myosin heads
o Continuous line of the myosin heads allows actin to slide along the myosin for longer distances
o Thick & thin filaments arranged diagonally, causing smooth muscle to contract in a corkscrew manner
o Myosin filaments have “side-polar” cross-bridges
▪ Cross-bridges on one side hinge in one direction & those on the other side hinge in the opposite
direction
● Allows myosin to pull an actin filament in one direction on one side while simultaneously pulling
another actin filament in the opposite direction on the other side
▪ Importance:
● Smooth muscle cells contract X 80% of their length
Electrical Basis for Smooth Muscle Contraction

● Adjacent smooth muscle cells exhibit slow, synchronized contractions
● Whole muscle sheet contracts as one
● Gap junctions transmit action potentials from cell to cell
● “pacemaker cells” found in smooth muscle cells of stomach & small intestines, act as “drummers” to
set the contractile pace for the whole muscle sheet
o Self-excitatory & depolarize without stimulus
Excitation-Contraction Coupling in Smooth Muscle

● Ca2+ sources: from SR & ECF
● 2+
Intracellular Ca interacts with regulatory molecules – calmodulin & myosin light chain kinase (MLCK)
o Calmodulin – Ca2+–binding protein
o Myosin light chain kinase – part of thick filament
● Absence of troponin complex in the actin filament makes the myofilaments ready for contraction
34
Sequence of Events in the Excitation-Contraction Coupling of Smooth Muscle
1. Ionic calcium (from ECF & SR) binds to calmodulin & activating it
2. Activated calcium-calmodulin activates the myosin light chain kinase (MLCK) enzyme
3. Activated myosin light chain kinase catalyzes phosphorylation – transfer of phosphate from ATP
(ADP+Pi) to myosin cross-bridges
4. Phosphorylated myosin cross-bridges interact with actin of the thin filaments, sliding of the
myofilaments creates muscle tension & produces shortening
5. Smooth muscle relaxation occurs when intracellular Ca2+ levels drops (calcium goes out of the cell back
to the ECF & back to the SR)
● Smooth muscle relaxation is a reverse process, except for the enzyme – phosphatase found abundant
in the sarcoplasm which splits phosphate from myosin light chain
Smooth Muscle Contraction vs. Skeletal Muscle Contraction

● Slow, prolonged & sustained contraction
● Slow cycling of myosin cross-bridges
● Energy required to sustain smooth muscle contraction
● Slowness of contraction & relaxation of the total smooth muscle tissue
● Force of muscle contraction
● Latch mechanism
Characteristic of Smooth Muscle Contraction

● Slow, prolonged & sustained contraction
● Resistant to fatigue
● Saves more energy used
o Sluggish ATPases (myosin light chain kinase)
o Latch mechanism of myofilaments during prolonged contraction
● Maintain smooth muscle tone (moderate degree of contraction in small blood vessels)
Slow Cycling of Myosin Cross-Bridges

● 1/10 to 1/300 frequency vs. skeletal muscle the frequency
● fraction of time that the cross-bridges remain attached to the actin filaments – increased
o major factor that determines the force of contraction in smooth muscles
● Myosin cross-bridge heads with less ATPase activity
o Degradation of ATP that energizes the movements of the cross-bridge heads is greatly reduced  slow
cycling of myosin cross-bridges
● Less energy used
Energy Requirement
● Less energy to sustain muscle tension during contraction
o Slow cycling of myosin cross-bridges
● Importance – saves overall energy of the body
o Intestines, urinary bladder, gallbladder & other viscera maintain indefinite tonic muscle contraction
Slow Onset of Smooth Muscle Tissue Contraction & Relaxation

● 30X longer vs. skeletal muscle fiber
35
● Slow onset & prolonged contraction due to:
o the slowness of attachment & detachment of the cross-bridges with the actin filaments
o Slower response to initiation of contraction by calcium ions
Force of Smooth Muscle Contraction

● Greater vs. skeletal muscle (despite few myosin filaments)
● Due to – prolonged period of attachment of the myosin cross-bridges to the actin filaments
Latch Mechanism
● Prolonged period of attachment of myosin cross-bridges with actin filaments
● Once smooth muscle has developed full contraction, the amount of continuing excitation usually can be
reduced to far less than the initial level, yet the muscle maintains its full force of contraction with less amount
of energy consumed to maintain contraction
● Maintains prolonged tonic contraction & tension in smooth muscles with less ATP use
● Sustains contraction without developing muscle fatigue
● Requires little continued excitatory neural or hormonal signals
Regulation of the Latch Mechanism

● Activated myosin light chain kinase (MLCK) & phosphatase enzymes increases the cycling frequency of
the myosin heads & the velocity of contraction
● Decrease activation of the enzymes, decreases the cycling frequency, but allows the myosin heads to
remain attached to the actin filament for a longer & longer proportion of the cycling period
● The number of myosin heads attached to the actin filament at any given time remains large.
● The number of myosin heads attached to the actin determines the static force of contraction, tension
is maintained, or “latched”
● Less energy used as ATP is not degraded to ADP +Pi
Regulation of Smooth Muscle Contraction
Neural Regulation
● In some, same with skeletal muscles
o AP is generated by neurotransmitter (ACh) binding
o Increase in intracellular Ca2+ in the sarcoplasm
● In some, responds with graded potentials (local electrical signals)
● Not all smooth muscle activation results from neural signals
● Different autonomic nerves release different specific neurotransmitters
o May either be excitatory or inhibitory to a particular group of smooth muscle cells in visceral organs
o Effects depends on the type of receptor molecules on the sarcolemma of smooth muscle cells
Acetylcholine/Norepinephrine – Excitatory neurotransmitter substances for smooth muscle fibers in some

organs but an inhibitory transmitter for smooth muscle in other organs
● When acetylcholine excites a muscle fiber norepinephrine ordinarily inhibits it
● Conversely, when acetylcholine inhibits a fiber, norepinephrine usually excites it
o ACh binds to receptors in smooth muscles in respiratory bronchioles causes bronchoconstriction,
narrowing the respiratory passages
o Norepinephrine (NE) released by a different type of autonomic fiber, binds to NE receptors on the same
smooth muscle cells, gives off inhibitory effect, causes relaxation of the respiratory bronchioles, dilating the air
passageways.
o NE binds to smooth muscles in the walls of most blood vessels; it stimulates the smooth muscle cells to
contract and causes vasoconstriction.
● Type of receptor determines whether the smooth muscle is inhibited or excited & determines which of
36
the two transmitters, acetylcholine or norepinephrine is effective in causing the excitation or inhibition
o ACh & norepinephrine both excite or inhibit smooth muscle by first binding with a receptor protein on
the surface of the muscle cell membrane – excitatory receptors/inhibitory receptors
Local Factors
● Some smooth muscle layers have no nerve supply & depolarizes spontaneously or in response to
chemical stimuli
● Chemical factors stimulate or inhibit smooth muscle contraction without an action potential by
enhancing or inhibiting calcium entry into the sarcoplasm
o Hormones/Lack of O2/Excess CO2 /Low pH
Local Tissue Factors

● Lack of O2 – causes smooth muscle relaxation  vasodilatation
● Excess CO2 – vasodilatation
● Increased H+ ion concentration – vasodilatation
● Adenosine, lactic acid,  K+ ions,  Ca2+,  body temperature – local vasodilatation
Effects of Hormones
● A hormone causes contraction of a smooth muscle when the muscle cell membrane contains
hormone-gated excitatory receptors for the respective hormone.
● A hormone causes inhibition if the membrane contains inhibitory receptors for the hormone
o Norepinephrine, epinephrine, acetylcholine, angiotensin, endothelin, vasopressin, oxytocin, serotonin,
histamine
● Direct response of smooth muscle to chemical stimuli alters muscle activity according to local tissue
needs
o Gastrin – stimulate smooth muscle in the stomach causes efficient digestion of foods
Special Types of Smooth Muscle Contraction
Special Features of Smooth Muscle Contraction

● Unique characteristics of smooth muscle include:
o Smooth muscle tone
o Slow, prolonged contractile activity
o Low energy requirements
o Response to stretch
Response to Stretch
● Cardiac muscle – vigorous contraction
● Skeletal muscle – contract by shortening (120% of resting length)
● Smooth muscle – contracts & moves substances along internal passageways
o Increased tension persists only briefly, & muscle adapts to its new length & relaxes, but retains ability
to contract on demand
Stress-Relaxation Response of Smooth Muscle

● Response to stretch
● Ability to return to nearly its original force of contraction after it has been elongated or stretched
● a phenomenon in which smooth muscle responds to stretch only briefly, & then adapts to its new
length which retains its ability to contract
● A hollow organ fills or expand slowly (within certain limits) to accommodate a greater volume without
promoting contractions that would expel the contents before proper functions takes effect
● enables organs such as the stomach & bladder to temporarily store contents
37
● Importance:
o Allow hollow organs to maintain the same amount of pressure inside its lumen despite long-term, large
changes in the length of muscle fibers.
Length and Tension Changes

● Smooth muscle stretches more & generates more tension than skeletal muscles
o Highly organized sarcomeres (skeletal muscles) limit how far can a muscle be stretched before it is
unable to generate force
o Lack of sarcomeres & irregular, overlapping arrangement of smooth muscle filaments generate
stronger force of contraction despite being stretched
● Degree of muscle stretch – muscles contract strongest when muscle fibers are 80-120% of their normal
resting length
● Skeletal muscle total length change is 60% (30% shorter to 30% longer than resting length) to function
effectively & efficiently
● Smooth muscle contract 2X its normal length to half its normal resting length (150%)
o Allow hollow organs to tolerate tremendous changes in volume without losing its tone when empty
Types of Smooth Muscles
● The smooth muscle of each organ is distinctive from that of most other organs in several ways:
o physical dimensions
o organization into bundles or sheets
o response to different types of stimuli
o characteristics of innervations
o function
Major Types of Smooth Muscle:

o Single-unit (unitary)
o multi-unit smooth muscle
Single-Unit Smooth Muscle

● UNITARY smooth muscle/Visceral smooth muscle/Syncytial smooth muscle
● mass of hundreds to thousands of smooth muscle fibers that contract together as a single unit
● Fibers are arranged in opposing sheets or bundles with their cell membranes adherent to one another
at multiple points
o Force generated in one muscle fiber can be transmitted to the next
● Cells of single-unit smooth muscle:
o Contract rhythmically as a single unit
o Electrically coupled to one another via gap junctions
▪ Ions moves freely from one cell to the other
o Often exhibit spontaneous action potentials from one cell to the other to make entire sheet of tissue
contract
Multi-Unit Smooth Muscle – are found:

o In large airways to the lungs
o In large arteries
o In arrector pili muscles
o Attached to hair follicles
o In the internal eye muscles (adjust pupil size & allow to visually focus)
● Characteristics of Multi-Unit Smooth Muscle

o Rare gap junctions
o Infrequent spontaneous & synchronous depolarizations
o Structurally independent muscle fibers
o Richly supplied with nerve endings, each of which forms a motor unit with a number of muscle fibers
38
o Responds to neural stimulation with graded contractions
o Autonomic (involuntary) nervous system innervations
o Responds to hormonal stimuli
MUSCLE PHYSIOLOGY: Cardiac Muscle
Cardiac Muscle vs. Skeletal Muscle

● Short branched fibers
● Single nucleus
● Intercalated discs
● Gap junctions
● Stimulation
o Pacemaker
o Autonomic
o Hormonal
    End of Unit 2 [Muscle Physiology]    

      
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Updated Notes On Physiology

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UNIT II: MUSCLE PHYSIOLOGY

Skeletal Muscle Tissue: striated, skeletal, & voluntary

Cardiac Muscle Tissue: cardiac, striated, involuntary

Smooth Muscle Tissue: visceral, non-striated, & involuntary

COMPARISON OF SKELETAL, CARDIAC, SMOOTH MUSCLE

CHARACTERISTICS SKELETAL CARDIAC SMOOTH

Voluntary; Involuntary, Involuntary;

Speed of contraction Slow to fast Slow Very slow

Rhythmic contraction No Yes Yes, in single-unit muscle

Contractile strength Contractile strength

MUSCLE PHYSIOLOGY: SKELETAL MUSCLE

Physical Structure and Function

Nerve and Blood Supply

Microscopic Anatomy of a Skeletal Muscle Fiber/Cell

SARCOLEMMA – cell membrane / plasma membrane surface

SARCOPLASM – cytoplasm with little cytosol

SPECIALIZED STRUCTURES in the Sarcoplasm:

SARCOMERE – “muscle segment”; smallest contractile unit of a muscle

Z disc – “Z” zwischen (German – between); coin-shaped sheet of proteins (connectins)

H zone – “H” helles (German – clear); “bare region”

M line – “M” mittel (German – middle)

ACCESSORY ELASTIC PROTEINS: Titin & Nebulin Molecules

TITIN molecules – huge, giant, filamentous proteins

NEBULIN molecules – inelastic giant protein

Ultrastructure & Molecular Composition of Myofilaments: MYOSIN & ACTIN FILAMENTS

Thick Filaments – composed of the bundled protein MYOSIN

Thin Filaments – chiefly composed of the contractile protein ACTIN

TROPONIN – attached along the sides of tropomyosin molecule

SARCOPLASMIC RETICULUM (SR) – Elaborate, highly specialized smooth endoplasmic reticulum

T Tubules (transverse tubules) – continuous with the sarcolemma

MUSCLE PHYSIOLOGY: Skeletal Muscle

STIMULATION & CONTRACTION OF SINGLE SKELETAL MUSCLE FIBERS

SKELETAL MUSCLE CONTRACTION

Functional Characteristics of Muscle Tissue

Major Steps in Skeletal Muscle Contraction:

The General Mechanism of Skeletal Muscle Contraction:

SLIDING FILAMENT THEORY OF SKELETAL MUSCLE CONTRACTION

Molecular Mechanism of Skeletal Muscle Contraction

MYOSIN FILAMENT: The Mechanism of Myosin Cross-Bridge Formation

ATP – Providing The Energy for Skeletal Muscle Contraction

MUSCLE METABOLISM: ATP – Energy for Contraction

Sources of ATP – Three (3) Pathways for ATP (re) generation:

1. Direct phosphorylation of ADP with creatine phosphate

Direct Phosphorylation of ADP by Creatine Phosphate:

Anaerobic Glycolysis & Lactic Acid Formation:

Sources of ATP: Aerobic Respiration – mitochondria

o Glucose + O2  CO2 + H2O + ATP

Energy Used During Sports Activities

Anaerobic + Aerobic – pathways intertwined

MUSCLE FATIGUE & OXYGEN DEBT

Muscle Fatigue – the muscle is in a state of physiological inability to contract

Muscle Fatigue: Factors / Causes – not fully known

Muscle Fatigue – occurs when:

Oxygen Debt / Oxygen Deficit

Heat Production during Muscle Activity

Axon – long threadlike extension of the neuron

Physiologic Anatomy of the Neuromuscular Junction

Secretion & Release of Acetylcholine:

Acetylcholine-Receptor Channel (refer to figure below)

Role of Acetylcholine (ACh)

Muscle Action Potential

Generation of MUSCLE Action Potential

Three Phases of an Action Potential across Sarcolemma