Muscle Physiology PDF

The Physiology of Muscles
Part III
Introduction
1. Introduction
1.1. General Points
a. Can be excited chemically, electrically + mechanically.
b. Contractile mechanisms (actin + myosin) that can be activated by AP.
1.2. Mass
a. 45-50% of the total body mass ( 600 muscles)
b. 40% skeletal muscles + 10% cardiac and smooth muscles (45-50%).
12/16/2023 The Physiology of Muscles 1

Part III
Introduction
1.3. O2 consumption
a. 25% total bodily O2 consumption at rest is consumed by the

muscles.
b. During strenuous exercise this amount can increase as much as
10-20 times.
2. Types/Classification
2.1. Anatomical
2.1.1. Striations:
Presence of alternating light and dark bands on the sarcolemma.

Part III
Introduction
2.1.1.1. Skeletal muscle
i. Have well developed cross striations (interdigitating thick and thin filaments).
ii. Voluntary muscle tissue.
iii. Cells are long and multinucleated.
iv. Contract only in response to stimuli (no syncytial bridges between cells).

Part III
Introduction
2.1.1.2. Cardiac muscle
i. Have cross striation (banding pattern of thick and thin filaments).

ii. Involuntary muscle tissue.
iii. Cells are branched and mononucleated.
iv. Have intercalated disc with gap junctions.
2.1.2. Non-striations/Smooth Muscle
Alternating dark and light bands are absent.

Part III
Introduction
2.1.2.1. Single unit smooth muscle (Visceral smooth muscle)

i. Are large sheets of mononucleated small cells.
ii. Have low resistance bridge of gap junctions.
iii. Show synch ronous excitation and contractions.
(= functional syncytium)
iv. Have unstable resting membrane potential.
v. Found in gut, ureter, small blood vessels and uterus.
2.1.2.2. Multiunit smooth muscles

i. Found in iris, lungs, hair roots and large arteries.
ii. Have no gap junctions but each cell receive ANS nerve terminal.
Part III
Introduction
2.2. Physiological
2.2.1. Voluntary Muscle
• Skeletal muscle (CNS, somatic neurons).
2.2.2. Involuntary muscle
• Cardiac muscle (Intrinsic + Extrinsic factors, ANS + Hormonal)

• Smooth muscle (Intrinsic + Extrinsic factors, ANS + Hormonal)

Part III
Skeletal Muscle
3.0. Skeletal Muscle

• Interactions between the body and the external environment
(maintenance of posture and movement, speech, respiration…).
3.1. Physiological classifications
3.1.1. Type I: Slow twitch oxidative fibers (red muscle)
i. Have slow myosin ATPase activity.
ii. High myoglobin content
iii. Many mitochondria and capillary
iv. Resistant to fatigue, high oxidative capacity
v. Muscles of the back and neck (strong gross sustained movt.)

Part III
Skeletal Muscle
3.1.2. Type IIA: Fast oxidative-glycolytic fibers (red fibers)

i. Fast myosin ATPase activity
ii. Fatigable fibers
iii. Use glycolytic and oxidative ATP sources
3.1.3. Type IIB: Fast glycolytic fibers (white muscles)

i. Fast velocity of contraction
ii. Fast myosin ATPase activity
iii. Glycolysis is the main ATP source
iv. Few myoglobin, mitochondria and blood vessels are present.
v. Muscles of the hand extraocular muscles (fine, rapid, precise movt.)

Structural arrangement and contractile unit
9
Structural arrangement and contractile unit
10
Part III
Skeletal Muscles
3.2. Structural arrangement and contractile unit

Muscle
↓ epimysium
Fasciculus (20 muscle fibers)
↓ perimysium
Muscle fiber (ɵ=10-100 µm, L=30cm, multinucleated)
↓ endomysium (Sarcolemma, sarcoplasm/myoplasm
Sarcoplasm reticulum
Myofibril (ɵ= 1-2µm, longitudinal, Sarcomere,
75% muscle vol., Z-line, α-actinin, desmin)
Myofilaments
Thick filaments Thin filaments

1500 molecules, myosin 3000 molecules, actin

Part III
Skeletal Muscles
Terms
1. Epimysium: a connective tissue which ensheaths the entire muscle.

2. Perimysium: a connective tissue that ensheaths the fascicles
3. Endomysium: a sheath that covers each muscle fiber.
• Each one is the continuation of the other.
4. Sarcoplasmic Reticulum: a tubular network that divides the individual
skeletal muscle fiber into myofibrils.
5. Sarcolemma: a true plasma membrane of skeletal muscle fiber.
6. α-actinin: a protein that connects actin to the z-line.
7. Myoplasm/sarcoplsam: cytoplasm of the muscle cell.

Part III
Skeletal Muscles
8. Desmin: a protein that links adjacent myofibrils, binding z

lines to plm
9. Myosin: the thick contractile protein.
10. Actin: the thin contractile protein.
11. Dystropin: actin binding protein linking transmembrane
protein, β-dystroglycan, in the sarcolemma with cytoplasmic
protein syntrophins (α-dystroglycan, (sarcoglycan, α, β, γ, δ))
12. Titin: Keeps the myosin and actin molecules in place
(prevents overstretching of sarcomere,)
13. Nebulin: a template protein which determines the precise

size of actin
Part III
Skeletal Muscles
3.3. Functional unit (Sarcomere)

a. It is the distance between two z-lines.
b. Responsible for the striated appearance.
3.3.1. Dimensions
a. The resting length of a sarcomere is 2µm-2.2µm.

b. At this length it generates the greatest force of contraction.

Part III
Skeletal Muscles
3.3.2. Molecular geometry

• Differences in Refractive indices when viewed under polarized
light.
A-Band (A= Anisotropisch)*
a. The darker area in the centre of the sarcomere.
b. It is due to the orderly arrangement of thick filaments.
c. Thin filaments may extend into the A-band.
H-Band(H = Hensen’s disc)
a. It contains only myosin tails (no myosin heads/no cross-bridges)
b. There are no thin filaments.
c. When the muscle is relaxed
* Germanic
12/16/2023 words The Physiology of Muscles 15
Part III
Skeletal Muscles
M-line (M= Mittelmembran)
a. Site of the reversal polarity of the myosin molecules in each of
the thick filaments.
b. It vertically bisects the H-Band
c. It contains 2 important proteins:
• Myomesin: a structural protein that links neighboring thick filaments
• Creatinine Phosphokinase: an enzyme that maintains adequate

ATP conc. in working muscle fibers.

Part III
Skeletal Muscles
I-Band (I= Isotropisch)

a. The lighter area on either side of the z-lines.
b. Each sarcomere contain half of the two I-bands.
Z-Line/Disc (Z = Zwischenscheibe)
a. Dense line in the center of each light band.

b. Separates one sarcomere from the next.
c. It is the attachment site for the thin filaments.

Geometrical orientation of the contractile elements
18
Geometrical orientation of the contractile elements
19
Myosin Actin
M line
Myofibril
The light and dark bands give skeletal and cardiac muscle their striated appearance.
Part III
Skeletal Muscles
NB
1. During muscular contraction:
a. There is NO CHANGE in length of either the thick or the thin
filaments.
b. H-zone disappears and Z-line gets considerably darker.
c. There is shortening of the sarcomere
(↓ I-band and H zone, and A-band remains κ)
2. a. When a muscle increases its length → ↑ in the No of sarcomeres
(NOT the length of each sarcomere)
b. The length of thick & thin filaments of sarcomeres is identical
in a neonate & in the adult muscle.

Part III
Skeletal Muscles
3.4. Molecular Basis of Contraction
3.4.1. Sliding-Filament Model (Hanson & Huxley, 1955)
This model theorizes that sliding in of the filaments (thick &

thin) toward the center of muscle and sarcomere is responsible
for the shortening and force of contraction.

Part III
Skeletal Muscles
3.4.2 Thick Filament

a. It is called myosin (an actin-binding protein).
b. Dimensions: ɵ = 11-18 nm, L = 1.6 µm
c. Composition of Myosin:
2 heavy chains = 200,000 x 2 = 400kd
4 light chains = 20,000 x 4 = 80kd
480kd
2 heads → Myosin head (cross-bridge) → Actin-binding site
→ ATP-binding site (ATPase) → Hydrolyzes ATP
1 long tail → form core of the thick filament
d. 1 thick filament has 300 myosin heads (294 in frog muscle).

1 cross-bridge has 2 identical heads
3 pairs of cross-bridge can bind 6 thin filaments
Myosin Filament
24
Part III
Skeletal Muscles
e. Orientation:
i. Head projects out on either side of the H-zone to rotate in

opposite directions to shorten the sarcomere.
ii. During rapid contraction each head form 5 cycles/sec, thus sliding
myosin & actin filaments by about 5µm/sec.
iii. In a resting muscle the cross-bridge is not attached to the thin

filaments & is oriented perpendicularly to the myosin filaments.
f. The thick filaments are suspended or assumed their central position

in the sarcomere because of their attachments to the z-disc by titin.

Part III
Skeletal Muscles
Geometrical orientation of myosin and actin

Geometrical orientation of myosin and actin
27
Part III
Skeletal Muscles
3.4.3. Thin Filaments

a. They are called actins.
b. Dimensions : ɵ = 5nm, L = 1 µm
c. Components :
1. Globular proteins
i. Actin (300-400 molecules, and molecular weight of 45kd)
Globular -Actin (G-actin) or
Fibrillar- Actin (F-actin, a polymer of G-actins)
ii. Troponin (50 molecules)
2. Non-Globular proteins: tropomyosin (40-60 molecules, 70kD)

Actin Filaments
29
Part III
Skeletal Muscles
3.4.4 Regulatory proteins

A. Tropomyosin
a. A rod-shaped molecule stretched along each strand of thin filament.
b. 1 tropomyosin molecule covers seven actin monomers in an actin filament.
c. It blocks the binding sites of myosin on actin.
B. Troponins
~ Small globular units located at intervals along the tropomyosin molecules.
a. Troponin T: it binds other troponin components to tropomyosin (37kD).
b. Troponin I: inhibits the interaction of myosin with actin (24kD)
c. Troponin C: it has the binding site for Ca2+ that initiates contraction (18kD)

Actins, Troponins and Tropomyosin Filaments
31
Part III
Skeletal Muscles
3.5. Molecular mechanisms of regulating muscle contraction
3.5.1. Regulatory Role of Troponin-Tropomyosin System
a. Resting state: Troponin I and Tropomyosin covers the sites where

myosin heads bind to actin.
(At rest: interaction of thick and thin filaments is inhibited).
• Troponin-Tropomyosin complex is called “Relaxing-Protein”

because it inhibits the interaction between myosin and actin.

Part III
Skeletal Muscles
b. Contractile state:
• The invading action potential to T-Tubule → Ca2+ released from

SR → binds to troponin C → binding of troponin I to actin is
weakened → tropomyosin moves laterally → uncovers binding
sites for myosin heads → contraction (in the presence of ATP).
• Seven myosin-binding sites are uncovered for each molecule of

troponin that binds a Ca2+.

Part III
Skeletal Muscles
3.5.2. Regulatory action of calcium

2 tubular networks (Sarcotubular system) that are involved with
Ca2+:
3.5.2.1. Transverse Tubule (T-tube)
a. It is an invagination of the surface of the muscle membrane
(sarcolemma).
b. It is found at the junction of A-band and I-band (at z-line in frog).

c. One end of the tube is open to the extracellular space, but its
other end is closed.
d. Function: Rapid transmission of the action potential from the
cell membrane to all the fibers on the muscle.

Part III
Skeletal Muscles
3.5.2.2. Sarcoplasm Reticulum (SR)

a. It is an internal tubular structure that runs between the myofibrils.
b. It is closed at both ends.
c. It is not continuous with the sarcolemma.
d. Functions:
i. Stores Ca2+ in the terminal cisternae
(lateral sacs, 1calsequestrin = 43 Ca2+ )
ii. Uptake and release of Ca2+
• Triad: 2 lateral sacs + 1 transverse tubule

Part III
Skeletal Muscles
3.5.3. Regulation of ATP

a. Actin + myosin + ATP + Ca2+ → CONRACTION
b. Actin + myosin + ATP - Ca2+ → RELAXATION
c. ATP is needed for relaxation
d. In the absence of Ca2+ ATP is not hydrolyzed.
e. 3 ATP molecules are needed:
i. For the formation of the actin-myosin complex
ii. For the initiation of relaxation.
iii. To pump out Ca2+ from the sarcoplasm to sequester it
into the SR (Ca2+ - Mg2+ pump)

Part III
Skeletal Muscles: ECC
3.6.1. Excitation-Contraction Coupling/

Electromechanical Coupling
Def. ~ is the process of linking ∆Em/AP to muscle contraction.

• Electrical events precedes mechanical events (2ms, 100ms)
• Twitch

Muscle Twitch
• Muscle contraction in
response to a
stimulus that causes
action potential in
one or more muscle
fibers
• Phases
– Lag or latent
– Contraction
– Relaxation
All skeletal muscles are composed of numerous fibres
ranging from 10-80um in diameter.
In most skeletal muscles each fibre extends the entire

length of muscle and each fibre is innervated by one
nerve ending located near the middle of the fibre.
The nerve cells whose axons innervate skeletal muscle

fibre are known as motor neurons(somatic efferent
neurons).
As the axon supplying a muscle fibre approaches its
termination it loses its myelin sheath and devides into a
number of terminal bouttons or end feet.
A motor neuron plus the muscle fibre it innervates is called

a motor unit
The end feet contain many small clear vesicles that contain
Ach.
The region of the muscle fibre plasma membrane that lies

directly under the terminal portion of the axon has special
properties and is called motor end plate
Skeletal Muscles: ECC Part III
Motor Unit
41
Propagation of AP into the T-tubule
Release of Ca from terminal cisternae of sarcoplasmic

reticulum and diffusion to thick and thin filaments
Binding of calcium to troponin C, uncovering myosin

binding site on actin
Formation of cross linkage between actin and myosin and

sliding of thin on thick filaments producing movement
43
Part III
Skeletal Muscles

Part III
3.6.4. The Activation of Muscle Proteins
3.6.4.1. Thick Filaments
a. Myosin (an actin binding protein)

b. 2 distinct structures:
• Myosin head (cross bridge): actin-binding site
• ATP binding site (ATPase): hydrolyzes ATP

Part III
Myosin and actin
46
47
Part III

Part III
3.6.4.2. Thin Filaments

a. Actins
b. Troponins:
Small globular units located at intervals along tropomyosin molecules.
i. Troponin T: it binds other troponin components to tropomyosin
ii. Troponin I: inhibits the interaction of myosin with actin
iii. Troponin C: it has the binding site for Ca2+ that initiates contraction
c. Tropomysoin
i. A rod-shaped molecule stretched along each strand of thin filament.
ii.1 tropomyosin molecule covers seven actin monomers
iii. It blocks the binding sites of myosin on actin.
50
Part III
Skeletal Muscles
51
Part III
Skeletal Muscles:ECC
Resting state
i. Interaction of thick and thin filaments is inhibited
ii. Troponin I & tropomyosin covers the sites where myosin heads bind to actin
Activated States:
Influx of Ca2+
↓
Binds to Troponin C (4 Ca2+)
↓
Conformational change in troponin
↓
Tropomyosin moves aside
↓
Exposes the myosin-binding sites on actin
↓
Myosin cross-bridge on the thick filament is exposed to actin filaments
52
Part III
3.6.5. Generation of Tension

Cross-bridge cycle: 4 steps
1. Binding of the cross-bridge to actin
A+M* . ADP. Pi A.M* + ADP + Pi
Actin binding
2. Bending of the cross-bridge producing movement of thin filament.
A. M*. ADP. Pi A.M*.+ ADP + Pi
Cross-bridge movement
3. Detachment of the cross-bridge from the thin filament

A.M+ ATP A+ M.ATP
Cross-bridge dissociation from actin
4. The cross-bridge returns to its original upright position to repeat the cycle.
M.ATP M*. ADP. Pi
ATP hydrolysis
NB. Tension is generated by repetitive cross-bridge cycling. 53
54
Part III
Relaxation of Muscle.
a. Removal of Ca2+ from the Myoplasm (<0.1µmol/l) into the SR.

b. For Ca2+ removal from the sarcoplasm the third ATP is consumed by
Ca2+-Mg2+ -ATPase
c. After removal of Ca2+ :
i. Troponin returns to its original conformational state.
ii. Tropomyosin inhibition of Myosin-Actin interaction is
restored.
iii. Cross-bridge cycling stops and the muscle is returned
to its resting state.
d. Breakdown of Ach by AchE.
Part III
Regulatory function of ATP
i. Actin + Myosin +ATP + Ca2+ Contraction
ii. Actin+ Myosin + ATP – Ca2+ Relaxation
iii. In the absence of Ca2+ ATP is not hydrolyzed.
iv. 3 ATP molecules are needed:
a. For energizing the myosin cross-bridges
b. For dissociation of actinmyosin complex and initiation of relaxation
c. To pump out Ca2+ from the sacroplasm to sequester it into the SR

(Ca2+-Mg2+ - pump)
Part III
Changes
a. Banding
• H-zone: Disappears
• Z-line: Gets considerably darker
• I-band: Narrower/smaller
• A-band: κ
b. Contractile proteins: NO CHANGE in length of myosin or actin
c. Sarcomere: Shortens

Changes in banding pattern
58
Part III
Changes in banding pattern

Part III
Summary
Discharge of motor neuron
↓
Release of Ach at motor endplate
↓
Binding of Ach to nAchR
↓
↑gNa+ and gK + in endplate membrane
↓
Generation of EPP
↓
Generation of AP in muscle fibers

Part III
Generation of AP in muscle fibers

↓
Inward spread of depolarization along T-tubules
↓
Release of Ca2+ from terminal cisterns of SR and diffusion to
thick and thin filaments
↓
Binding of Ca2+ to troponin C, uncovering myosin-binding
sites on actin
↓
Formation of cross-linkages between actin and myosin and
sliding of thin on thick filaments, producing movement

Part III
Steps in relaxation
Ca2+ pumped back into SR

↓
Release of Ca2+ from troponin
↓
Cessation of interaction between actin and myosin

The Physiology of Synaptic Transmission
Neurotransmitters Part II
Clinical Correlates
1. Lambert-Eaton Syndrome
a. ↑Abs against Ca2+ channels in the presynaptic nerve endings at
NMJ →  density of VG Ca2+ channels.
b.  Ca2+ influx →  Ach release → muscle weakness
2. Myasthenia gravis :
An autoimmune disorder of NMJ caused by:
a. Abs against nAchR →  nAchR on the postjunctional membrane →
EPP.
b. Weakness and inability to sustain muscle contraction.
12/16/2023 The Physiology of Synaptic Transmission 63

Part III
Skeletal Muscles: Clinical correlates
Rigor Mortis
a. It is a state of muscle contracture, ie., contraction produced without

AP and not followed by relaxation.
b. It is a contracture which occurs in the muscles after death. It starts in

small muscles (2-3hrs) after death and involves all muscles in 12 hrs.
c. The rigidity is due to depletion of ATP from the muscle. Calcium

diffuses out of the SR & can not be recollected by the calcium pump.
d. Calcium initiates muscle contraction using the remaining ATP

molecules, relaxation does not occur because calcium is not
recollected back into the SR, and no ATP is available to disconnect
the myosin heads from actin.
Part III
Skeletal Muscles: Clinical correlates
e. It disappears when muscle fibers are autolysed by lysosomal

enzymes released after death.
f. It starts to disappear 14hrs after death and completed in 24hrs.
The extent of rigor mortis is used medically to determine the time

of death.

Part III
Cardiac Muscle
CARDIAC MUSCLE
Introduction
a. The physiological basis of heart pumping (contracting of the heart) is
to propel blood through the circulatory system.
b. It has SAME contractile machinery with some degree of modification.
(Actins, myosin, meromyosin, c-protein, nebulin, α-actinin, tropomodulin…)
c. REGULATION is done by intrinsic and extrinsic factors: neuronal

(ANS) + hormonal.

Part III
Cardiac Muscle
Cardiac Muscle Vs Skeletal Muscle

Cardiac Muscle.
1. A cardiac myocyte has a single nucleus which is smaller (ɵ = 15-20
µm, L = 100µm)
2. Has abundant amount of mitochondria (30%) + myoglobin which
makes it fatigue resistant (myoglobin facilitates the transport of
oxygen from the sarcolemma to the mitochondria)
3. A cardiac cells are joined end-to-end by intercalated discs:
i. Attach one cell to the next by means of desmosomes
ii. Connect the thin filament of the myofibrils of adjacent cells.
(Mechanical + electrical coupling)

Combines properties of both skeletal and smooth muscle
Cells are striated

Arrangement of thin and thick filaments is similar to that
of skeletal muscle,
Cardiac muscle cell are shorter than skeletal muscle fibres
Adjacent cells are joined end to end at intercalated disk

within which are desmosomes that hold the cells together
and to which the myofibrils are attached.
Adjacent to intercalated disks are gap junctions

69
Part III
Cardiac Muscle

The Physiology of Nerve Cells
Neuronal Signaling Part I
12/16/2023 The Physiology of Nerve Cells 71

The Physiology of Nerve Cells
Neuronal Signaling Part I
4. Action Potentials with Plateau

Plateau prolongs the period of depolarization
Reasons :
i. Fast channels: Voltage-gated Na+ channels → spike portion of AP
Slow channels: Voltage-gated Ca2+ channels (L-type) →

Ca2+-Na+ channels→ ↑ gCa2+ → plateau
ii. Voltage-gated K+ channels: slow/delayed opening.
iii. Gap junctions synchronizes the contractions of heart muscle cells.
12/16/2023 The Physiology of Nerve Cells 72

Part III
Cardiac Muscle
5. The T-tubule is larger and it is found at z-line. Inside T tubules there

are large quantities of negatively charged much polysacharides which
bind to Store Calcium.
6. The SR - makes contact with T-tubule and the cell membrane. The SR
of cardiac muscle is less well developed than skeletal muscle and does
not store enough Ca to provide full contraction.
The strength of contraction of cardiac muscle depends to a great

extent on the concentration of Ca ions in the ECF.

Cardiac Muscle Part III
4.3. Excitation-Contraction Coupling/Electrochemical Coupling
4.3.1. Cardiac Muscle.

1. Ca2+- release from the SR is triggered by Ca2+ (not by membrane
depolarization; extracellular Ca2+ →SR (is responsible for
prolonged plateau phase). Ca induced Ca release
2. T-Tubule contains Ca2+ channel (through which Ca2+ enters
the cell during the AP).
3. SR containing Ca2+- release channel is opened by influx of Ca2+

from the T-Tubule.
The Ca combines with the regulator protein troponin and the cross bridge
formation between actin and myosin is initiated.

Part III
Smooth Muscles
5.0. SMOOTH MUSCLE
5.1. Introduction
a. It is important in regulation of the airways, blood vessels, GIT, and

hollow organs (bladder, uterus...)
b. It is controlled by intrinsic factors (inherent rhythmicity): ANS +

HORMONES.
c. It produces slower and longer-lasting contractions (slow and

sustained) (↓rates of cross-bridge cycling → LATCH STATE →
maintain TONE and little energy consumed)

Part III
Smooth Muscles
5.2. Smooth Muscle Vs Striated Muscle.
5.2.1. Smooth Muscle.
1. It has NO STRIATIONS (sparse thick filaments and absence of

transverse registration).
2. Has elongated spindle shaped cells with a single nucleus

(L = variable size, attached in series to bear equal stress).
3. Sarcomeres are absent.
4. T tubules are absent and the SR is rudimentary

Part III
Smooth Muscles
4. The myofilaments are :

a. Thick filaments: myosin
b. Thin filaments: actin and tropomyosin (No troponin)
c. Thick and thin filaments are dispersed through out the cell.
They are not arranged in strictly ordered pattern.
d. Thin filaments are attached to dense bodies
(functional equivalents of Z)

Part III
Smooth Muscles
80
81
82
Part III
Smooth Muscles
5.3. Excitation - Contraction Coupling (Smooth M.Vs Striated M.)

• Cross-bridge cycling is regulated by Ca2+- induced phosphorylation of myosin.
1. Myosin cross-bridge has 4 light chain
2. Myosin can not bind to actin unless one of these light chains
(LC20) is phosphorylated.
a. Phosphorylation of LC20 is by Myosin Light Chain
Kinase (activated by Calmodulin, calmodulin - Ca2+-
complex)
b. Ca2+ can enter the cell in a variety of ways:
i. Stimulation by a neurotransmitter
ii. Voltage-operated Ca2+channels
iii. Release from SR (SR-IP3R)
3. The light chains are dephosphorylated by the enzyme Myosin Light
Chain Phosphorylase.
EXCITATION-CONTRACTION COUPLING OF SMOOTH MUSCLE
FIBERS
Contraction-Relaxation – myosin based regulation
Ca2+
Ca2+
calmodulin
Relaxation
MLC inactive
(dephosphorylated)
MLCP MLCK
MLC active
(phosphorylated)
Contraction
MLCK, myosin light chain kinase
MLCP, myosin light chain phosphatase
Comparison of Smooth muscle contraction and
Skeletal muscle contraction
• Slow cycling of the myosin cross-bridges
– as little as 1/10 to 1/300 that in skeletal muscle
– less ATPase activity than in skeletal muscle
• Low energy requirement to sustain smooth muscle
contraction
– one molecule of ATP is required for each cycle.
• Slowness of onset of contraction and relaxation of smooth
muscle contraction
– about 30 times as long as a single contraction of an average
skeletal muscle fiber’.
– is caused by the slowness of attachment and detachment of the
cross-bridges with the actin filaments
• Maximum force of contraction is often greater in smooth
muscle than in skeletal muscle
– results from the prolonged period of attachment of the myosin
cross-bridges to the actin filaments.
• “LATCH” Mechanism facilitates prolonged
holding of contractions of smooth muscle
– Little continued excitatory signal is required from
nerve fibers or hormonal sources.
– with little use of energy.
• Stress-Relaxation of smooth muscle
– is its ability to return to nearly its original force of
contraction seconds or minutes after it has been
elongated or shortened.
Summary ECC smooth muscle
Binding of Ach to mAchR

↓
Increased Ca2+ influx into the cell
↓
Activation of calmodulin-dependent myosin light chain kinase
↓
Phosphorylation of myosin
↓
Increased myosin ATPase activity and binding of myosin to actin
↓
Contraction
↓
Dephosphorylation of myosin by myosin light chain phosphatase
↓
Relaxation, or sustained contraction due to the latch bridge and other
mechanisms 93
Mechanics of contraction
The force exerted on an object by a contracting muscle is

muscle tension
The force exerted on the muscle by an object is the load
Types of Contraction
Isometric contraction
When the muscle does not shorten but develops
tension.
Occur when the muscle supports a load in a constant
position or attempts to move a load that is greater than
the tension developed by a muscle.
Isotonic contraction: the muscle contracts but the tension on the

muscle remains constant eg lifting weight
Muscle Contraction Types
Isotonic contraction
Tension
Isotonic Contraction
Skeletal muscle changes length:
resulting in motion
If muscle tension > load (resistance):
muscle shortens (concentric contraction)
If muscle tension < load (resistance):
muscle lengthens (eccentric contraction)
Muscle Contraction Types
Skeletal muscle develops tension,
but is prevented from changing
length
Note: iso- = same, metric = measure
Produces no movement
Used in
Standing
Sitting
Posture
Summation of muscle contraction
The increase in muscle tension from successive APs

occurring during the phases of mechanical activity is
known as summation.
Occurs if a second stimuli is applied during

contraction period, the two contractions are summed
up a single curve is obtained.
Amplitude of summation curve is greater than that of
simple muscle curve
Tetanus
A maintained contraction in response to repetitive
stimulation of high frequency. Multiple stimuli at higher
frequency and succesive stimuli fall during contraction
period of previous twitch, the muscle remains in stae of
tetanus.
Fatigue
The decrease in muscular activity due to repeated
stimuli.
Cause
1. Exhaustion of Ach in motor end plate
2. Accumulation of metabolites like lactic acid
3. Lack of nutriens
4. Lack of oxygen
Muscle Fatigue
Tetanus
Length Tension Relationship
Stretching a relaxed muscle
Length–tension relationship
fibre pulls the thin filaments
past the thick filament. No -Number of pivoting cross-bridges
overlap
depends on:
As more filaments overlap the amount of overlap between thick and thin
tension developed increases in fibers
proportion to the increased -Optimum overlap produces greatest
number of cross bridges in the
amount of tension:
overlapped region
too much or too little reduces efficiency
Filament ovelap is greater at -Normal resting sarcomere length:
2um allowing the maximum No is 75% to 130% of optimal length
of cross bridge to bind to thin
filament thereby producing
maximal tension
Tension declines at length less than 2 bcs
1. The overlapping sets of thin filaments from opposite

ends of the sarcomere may interfere with the cross
bridges’s ability to bind and exert force
2. The affinity of troponin for Ca decrease at short fibre
length

Muscle Physiology PDF

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Muscle Physiology PDF

Uploaded by

Copyright:

Available Formats

The Physiology of Muscles

a. 45-50% of the total body mass ( 600 muscles)

b. 40% skeletal muscles + 10% cardiac and smooth muscles (45-50%).

12/16/2023 The Physiology of Muscles 1

a. 25% total bodily O2 consumption at rest is consumed by the

12/16/2023 The Physiology of Muscles 2

2.1.1.1. Skeletal muscle

ii. Voluntary muscle tissue.

iii. Cells are long and multinucleated.

12/16/2023 The Physiology of Muscles 3

2.1.1.2. Cardiac muscle

i. Have cross striation (banding pattern of thick and thin filaments).

2.1.2. Non-striations/Smooth Muscle

Alternating dark and light bands are absent.

12/16/2023 The Physiology of Muscles 4

2.1.2.1. Single unit smooth muscle (Visceral smooth muscle)

2.1.2.2. Multiunit smooth muscles

2.2.1. Voluntary Muscle

• Skeletal muscle (CNS, somatic neurons).

2.2.2. Involuntary muscle

• Cardiac muscle (Intrinsic + Extrinsic factors, ANS + Hormonal)

12/16/2023 The Physiology of Muscles 6

3.0. Skeletal Muscle

12/16/2023 The Physiology of Muscles 7

3.1.2. Type IIA: Fast oxidative-glycolytic fibers (red fibers)

3.1.3. Type IIB: Fast glycolytic fibers (white muscles)

12/16/2023 The Physiology of Muscles 8

3.2. Structural arrangement and contractile unit

Thick filaments Thin filaments

12/16/2023 The Physiology of Muscles 11

1. Epimysium: a connective tissue which ensheaths the entire muscle.

12/16/2023 The Physiology of Muscles 12

8. Desmin: a protein that links adjacent myofibrils, binding z

13. Nebulin: a template protein which determines the precise

3.3. Functional unit (Sarcomere)

a. The resting length of a sarcomere is 2µm-2.2µm.

12/16/2023 The Physiology of Muscles 14

3.3.2. Molecular geometry

• Myomesin: a structural protein that links neighboring thick filaments

• Creatinine Phosphokinase: an enzyme that maintains adequate

12/16/2023 The Physiology of Muscles 16

I-Band (I= Isotropisch)

a. Dense line in the center of each light band.

12/16/2023 The Physiology of Muscles 17

12/16/2023 The Physiology of Muscles 21

3.4. Molecular Basis of Contraction

3.4.1. Sliding-Filament Model (Hanson & Huxley, 1955)

This model theorizes that sliding in of the filaments (thick &

12/16/2023 The Physiology of Muscles 22

3.4.2 Thick Filament

d. 1 thick filament has 300 myosin heads (294 in frog muscle).

i. Head projects out on either side of the H-zone to rotate in

iii. In a resting muscle the cross-bridge is not attached to the thin

f. The thick filaments are suspended or assumed their central position

12/16/2023 The Physiology of Muscles 25

Geometrical orientation of myosin and actin

12/16/2023 The Physiology of Muscles 26

3.4.3. Thin Filaments

12/16/2023 The Physiology of Muscles 28

3.4.4 Regulatory proteins

12/16/2023 The Physiology of Muscles 30

3.5. Molecular mechanisms of regulating muscle contraction

3.5.1. Regulatory Role of Troponin-Tropomyosin System