It includes the basic anatomy physiology of skeletal muscles, the thorough working of the muscles, at superficial level to molecular level, the energy input, smooth muscle-cardiac-skeletal muscles differences, smooth muscle anatomy physiology.

1. PRESENTED BY:
NIYAMAT M.A CHIMTHANAWALA
M.PH I (PHARMACOLOGY)
DEPT. OF PHARMACEUTICAL SCIENCES,
NAGPUR UNIVERSITY
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2. CONTENTS
 SKELETAL MUSCLES
A. Physiological anatomy
B. General Mechanism
C. Molecular Mechanism
D. Interaction of filaments and Calcium ions
E. Energetics
F. Characteristics of Whole Muscle Contraction
G. Specialties of contraction
H. The Neuromuscular junction
I. Molecular Biology of Ach Formation & Release
J. Muscle Action Potential
K. Contraction-Excitation Coupling
 SMOOTH MUSCLES
A. Types
B. Contractile mechanism of Smooth muscle
C. Nervous and Hormonal Control of Smooth Muscle Contraction
D. Effect of Local Tissue Factors and Hormones on Contraction
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3. PHYSIOLOGICAL ANATOMY OF SKELETAL MUSCLES
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a) Connective tissue
sheaths
b) Sarcolemma
c) Myofibrils- Actin
& Myosin
filaments
d) Sarcoplasm
e) Striations,
Sarcomeres
f) SR, T tubules
a) Connective Tissue sheaths
■ Epimysium- an “overcoat” of dense irregular connective tissue, surrounding the whole muscle.
Sometimes it blends with the deep fascia that lies between neighboring muscles or the superficial
fascia deep to the skin.
■ Perimysium and fascicles- (bundles of sticks), the grouped muscle fibers within each skeletal
muscle. Surrounding each fascicle is a layer of fibrous connective tissue called perimysium.
■ Endomysium (wispy sheath of areolar connective tissue) surrounding each individual muscle
fiber.
Bright Myomesin

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PHYSIOLOGICAL ANATOMY OF SKELETAL MUSCLES
STRIATED
APPEARANCE
Sarcomere-the functional unit
of skeletal muscle.

5. b) Sarcolemma (cell membrane of the muscle fiber)
Contains outer coat of numerous thin collagen fibrils. At each end of the muscle fiber, sarcolemma fuses with
tendon fiber, tendon fibers bundles form the muscle tendons that then insert into the bones.
c) Myofibrils (1–2 μm in diameter),
Thick filaments 16nm diameter .Each thick filament contains about 300 myosin molecules
bundled together. Each myosin molecule 4,80,000 MW ,consists of 2 heavy 200,000 MW each & 4 light
polypeptide chains 20,000 MW each, and has a rod like tail attached by a flexible hinge to two globular heads .The
tail consists of two intertwined helical polypeptide heavy chains.
Form cross bridges and swivel at point of attachment.
Thin filaments (7–8 nm thick) of actin mostly. Kidney shaped
polypeptide subunits-globular actin or G actin, (the active sites to attach
to during contraction; 42,000 MW each).
G actin subunits polymerized into long actin filaments called filamentous, or F,
actin. Two intertwined actin filaments, resembling a twisted double strand of pearls, form the backbone of each thin
filament.
Thin filaments also contain several regulatory proteins.
■ Tropomyosin a rod-shaped protein, spiral about actin core help
stiffen and stabilize it. Molecules arranged end to end along the actin filaments,
In relaxed muscle fiber, block myosin-binding sites on actin.
■ Troponin a globular three-polypeptide complex.
(TnI) inhibitory subunit binds to actin.
(TnT) binds to tropomyosin and helps position it on actin.
(TnC) binds calcium ions.
■ Titin elastic element;very springy filamentous molecules 30,00,000 MW hold the filaments in place. Extends
from Z attaches to M line.
d) Striations, Sarcomeres, and Myofilaments
Striations, a repeating series of dark A bands and light I bands.
■ A band has the H zone and M line.
■ I band has the Z disc (or Z line).
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6. e) Sarcoplasmic Reticulum is an elaborate ER.
Most SR tubules run longitudinally along the myofibril, communicating with each other at the H zone. Others
called terminal cisterns (“end sacs”) form larger, perpendicular cross channels at the A band–I band junctions
and they always occur in pairs.
CALSEQUESTRIN-a protein in SR which binds Ca2+ 40 times more.
f) T Tubules At each A band–I band junction, the sarcolemma of the muscle cell protrudes deep into the cell
interior, forming an elongated tube; increase the muscle fiber’s surface area. Fusing tubelike caveolae,
the lumen (cavity) is continuous with the extracellular space. Along its length, each T tubule runs between the
paired terminal cisterns of the SR, forming triads, successive groupings of the three membranous structures
(terminal cistern, T tubule, and terminal cistern). As they pass from one myofibril to the next, the T tubules
carry nerve impulses to deepest regions of cell.
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8. DIFFERENCES BETWEEN TYPES OF MUSCLES
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1 tubule/sarcomere
2 tubules/sarcomere

9. 1. ACTION POTENTIAL TRAVELS FROM NERVE ENDINGS
TO MUSCLE FIBERS
2. RELEASE OF NEUROTRANSMITTER ACH
3. DENSE BARS (Ca2+ RELEASE) ACH ACTS ON
RECEPTOR (Ach gated cation channel)
4. ACH BINDS; LARGE INFLUX OF Na+ IONS
5. A.P TRAVELS ALONG MUSCLE FIBER SIMILAR TO NERVE
6. A.P TRAVELS DEEP TO S.R; Ca2+ RELEASE
7. Ca2+ INITIATES CONTRACTILE PROCESS (actin-myosin
slide along each other)
8. Ca2+ PUMPS BACK INTO S.R; CONTRACTION CEASES
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AFTER ACTION
POTENTIAL,FORMATION
OF ACH AND ITS
RELEASE

11. MOLECULAR MECHANISM
Sliding filament mechanism of muscle contraction
 Molecular Characteristics of the Contractile
Filaments
A. Myosin filament 1.6 micrometres, crossbridges
(axially displaced at 120 degrees) -2 pts of
attachment (hinges)
B. ATPase Activity of the Myosin Head-head acts as
an ATPase enzyme
C. Actin filament 1 micrometre; 2.7nm dist. Between
2 active sites.
D. Tropomyosin molecules MW 70,000; 40nm length
E. Troponin: role in muscle contraction; 3 subunits
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14. Interactionof One Myosin Filament,
Two Actin Filaments, and CalciumIons
to Cause Contraction
 Presence of Mg2+ and ATP –binding occurs instantly.
 Presence of Troponin-Tropomyosin complex on Active
sites of actin inhibits binding.
 Ca2+ inhibits the complex; facilitates binding and
contraction.
 Walk-along “ratchet theory” of contraction-tilt of the head
(power stroke) -- two ends of actin filament towards
centre of myosin filament.
 No. of cross bridges proportional to force of contraction.
 Fenn effect- amt of ATP cleaved proportional to the work
done.
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15. ATP as the Source of Energyfor Contraction—Chemical Events in the Motionof
the MyosinHeads.
 ATP cleavage- ADP + iP; the head is
perpendicular but not attached to actin
 Ca2+ complex binding reveals active sites;
myosin binds
 Head conformational change; tilt called
power stroke
 Tilt releases ADP; new ATP replaces it
 Binding of ATP leads to detachment of head
from actin
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16. Work Output During Muscle Contraction
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W = L x D
 Efficiency of contraction is best when velocity is moderate about 30%
 Sources of Energy for Muscle Contraction
a. ATP 4mM –duration of full muscle contraction 1-2 sec
b. Phosphocreatine approx 20mM –duration of 5-8 sec
c. Glycogen breakdown, even in absence of O2 –few sec to a min
formation of ATP 2.5times faster
d. Oxidative metabolism of fats,proteins, carbohydrates –duration 2-4
hrs
Relation of load to velocity of contraction in skeletal muscle with a
cross section of 1 sq cm and a length of 8 cm.

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Characteristicsof Whole Muscle Contraction

19. 1.Isometric Versus Isotonic Contraction.
2.Characteristics of Isometric Twitches Recorded from Different Muscles.
3.Fast Versus Slow Muscle Fibers.
4.Mechanics of Skeletal Muscle Contraction
5.Muscle Contractions of Different Force—Force Summation. Multiple fiber
summation vs Frequency summation.
6.Maximum Strength of Contraction.
7.Changes in Muscle Strength at the Onset of Contraction—The
8.Staircase Effect (Treppe).
9.Skeletal muscle tone.
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Duration of isometric contractions for different types of mammalian
skeletal muscles, showing a latent period between the action
potential (depolarization) and muscle contraction.

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21. MUSCLE SPECIALTIES
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HYPERTROPHY –Total mass enlarges
Either due to exertion or muscle stretched greater than normal
Remodeling of muscles can occur within 2 weeks.
ATROPHY-Muscle mass decreases, rate of decay of proteins high,
unused for long
DENERVATION ATROPHY-Complete loss of function within 2yrs
HYPERPLASIA- Extreme muscle force generation
POLIOMYELITIS- Some nerve fibers destroyed
RIGOR MORTIS-Contracture; loss of ATP
MYASTHENIA GRAVIS-autoimmune disease; patients develop
anitbodies against Ach activated ion channels. Death might occur
due to paralysis of respiratory muscles.
CONDITION NERVE FIBERS SKELETAL MUSCLE
RESTING MEMBRANE
POTENTIAL
-80 TO -90 mv -80 TO -90 mv
DURATION OF A.P 5 TIMES FASTER 1-5 msec
VELOCITY OF
CONDUCTION
MUCH FASTER 1/13TH THAT OF
MYELINATED NERVE
FIBERS

22. THE NEUROMUSCULAR TRANSMISSION
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IN RELAXED STATE Ca2+ CONC 10^-7 M; CONTRACTED STATE 10^ -4 M;
500 FOLD MORE
Ca2+ PULSE LASTS 1/20TH OF A SEC IN SKELETAL MUSCLES

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NM
JUNCTION
• NERVE FIBER INNERVATION TO MUSCLE FIBER; MOTOR END PLATE
• SYNAPTIC GUTTER SYNAPTIC CLEFT (30nm)
NM
JUNCION
• SMALLER FOLDS AROUND MUSCLE MEMBRANE (SUB NEURAL CLEFTS)
• 3,00,000 VESICLES (40 nm)AT A TIME AT SINGLE TERMINAL END PLATE
• 10,000 MOLECULES OF ACH IN EACH VESICLE
ACH
SECRETIO
N
• 125 VESICLES RELEASE UPON STIMULUS
• DENSE BARS ON INSIDE OF NERVE MEMBRANE CONTAIN VOLTAGE GATED Ca2+
CHANNELS
• Ca2+ ENTRY 100 FOLD; ACH 10,000 FOLD ENTRY
• Ca2+ ENTRY PROMOTES EXOCYTOSIS
ACH GATED
ION
CHANNELS
• 2,75,000 MW PROTEIN COMPLEX, 5 SUBUNITS 2a,B,g,d
• 2 ACH MOLECULES BIND; CONF CHANGE
• 0.65 nm DIAMETER OF OPEN ACH CHANNEL
• LARGE QUTY Na+ FUSE INSIDE DUE TO -VEITY
MEMBRAN
E
• ACH FEW MSEC IN SYNAPSE BEFORE DEGRADATION BY ACHE
• ACTION POTENTIAL GENERATED AT LOCAL AREA OF END PLATE +50 TO +75 mV
MUSCLE
• HIGH SAFETY FACTOR OF MUSCLE-3 TIMES THE AMT OF END PLATE POTENTIAL
REQD
• FATIGUE DUE TO STIMUALTION GREATER THAN 100 TIMES/SEC
NM
JUNCTION
• NO. OF VESICLES SUFFICIENT FOR THOUSANDS OF IMPULSES
• CLATHRIN COATED PITS FORM NEW VESICLES
• ENTIRE PROCESS OCCURS IN 5-10 MSEC.

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25. Contraction and Excitation
of Smooth Muscle
1. 1-5 micrometres diameter and 20-500 micrometres length
2. Diffusion occurs at 200-300 msec rate of Ca2+ inside along the conc
gradient.
3. Types-
a) Multi unit smooth muscle discrete (separate fibers covered by collagen like glycoprotein)
ex:ciliiary muscles, iris muscles, piloerector muscles. Nervous stimuli
b) Single unit smooth muscle (hundred thousands of muscle fibers contract together) . Non-
nervous stimuli
Also called syncytial smooth muscle because of its syncytial interconnections among fibers.
Also called visceral smooth muscle because it is found in the walls of most viscera of the
body, including the gut, bile ducts, ureters, uterus, and many blood vessels.
4. The dense bodies of smooth muscle serve the same role as the Z discs in
skeletal muscle.
5. Most myosin filaments have “sidepolar” cross-bridges; the bridges on one
side hinge in one direction and the other side hinge in the opposite direction.
80% length contracted.
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26. COMPARISON OF SMOOTH MUSCLE CONTRACTION
AND SKELETAL MUSCLE CONTRACTION
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27. 5. “Latch” mechanism for prolonged holding of contractions of
smooth muscle-
 Even after deactivation of enzymes ,Myosin kinase and Myosin
phosphatase, myosin heads remain attached for prolonged period
(few hrs) creating “static” force of contraction utilizing minimal
energy ATP
6. The phenomena of stress relaxation and reverse stress-relaxation
Ex.urinary bladder
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30. REGULATION OF CONTRACTION BY CALCIUM IONS
 Increase in Ca2+ due to:- Nervous or Hormonal Stimulation, stretch
of the fiber or change in chemical environment.
 Combination of Calcium Ions with Calmodulin—causes activation of
Myosin Kinase , Phosphorylation of 1 light chain of each Myosin
head, cause intermittent pulls.
 Cessation of Contraction—Role of Myosin Phosphatase, splits
phosphate group from head, level of Ca2+ very low.
 Neuromuscular Junctions of Smooth Muscle- different from skeletal,
autonomic nerve fibers innervate-secrete Ach and NA, penetration in
diffuse junctions.
 Ach and NA secrete from different fibers always and can be
excitatory/inhibitory as per receptor protein.
 Fine terminal axons have multiple varicosities ,secretion of transmitter
through walls.
 Contact junctions 20-30 nm wide act as the NM junction space
between muscle membrane and varicosities.
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NERVOUS AND HORMONAL CONTROL OF SMOOTH
MUSCLE CONTRACTION

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MECHANISM OF ACTION

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33. MEMBRANE POTENTIALS AND
ACTION
POTENTIALS IN SMOOTH MUSCLE
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In unitary smooth muscle-
A. Spike Potential 10-50 msec
B. Slow wave rhythm of smooth muscle
fibers, not self regenerating, but localized,
pacemaker waves in gut.
C. It has plateau phase which can account
for prolonged contraction, large no.
voltage gated Ca2+ ch. more 1000
msec.(cardiac,uterus,vascular muscles)
D. Muscle stretch causes automatic
generation of muscle A.P
In multi unit smooth muscle-
A. The local depolarization (the junctional
potential) by nerve fibers on small muscle
fibers

34. EFFECT OF LOCAL TISSUE FACTORS AND
HORMONES TO CAUSE SMOOTH MUSCLE
CONTRACTION WITHOUT ACTION
POTENTIALS
 Hormones norepinephrine, epinephrine,
acetylcholine,angiotensin, endothelin,
vasopressin, oxytocin, serotonin, and
histamine.
 Lack of O2, Excess CO2, Increased H+,
Adenosine, lactic acid, increased K+,
diminished Ca2+, and increased body
temperature can all cause local
vasodilatation.
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35. REFERENCES
 GUYTON TEXTBOOK OF MEDICAL
PHYSIOLOGY,11TH ED.
 MARIEB HUMAN ANATOMY AND
PHYSIOLOGY,10TH ED.
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36. “THE ONLY PERSON YOU SHOULD TRY TO
BE BETTER THAN, IS THE PERSON YOU
WERE YESTERDAY.”
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