Muscle physiology

1. Muscle physiology
Dr. Dina Hamdy Merzeban
Lecturer of physiology Fayoum university
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‫تاني‬
http://slideshare.net/merzeban

2. MOTOR UNIT:
THE NERVE-MUSCLE FUNCTIONAL UNIT
• A motor unit is a motor neuron and all
the muscle fibers it supplies
• The number of muscle fibers per
motor unit can vary from a few (4-6)
to hundreds (1200-1500)
• Muscles that control fine movements
(fingers, eyes) have small motor units
• Large weight-bearing muscles
(thighs, hips) have large motor
units
• Stronger and stronger contractions
of a muscle require more and
more motor units being stimulated
(recruited)

3. • The skeletal muscle fibers are innervated
by large myelinated nerve fibers that
originate from large motor neurons in the
anterior horn of spinal cord
• Each nerve ending makes a junction called
neuromuscular junction with the muscle
fiber near its mid point
• Action potential initiated in the muscle fiber
by the nerve signal travels in both the
direction towards the muscle fiber length
• There is one such junction per muscle fiber
NEUROMUSCULAR
JUNCTION

4. NEUROMUSCULAR JUNCTION
(MOTOR END PLATE)
• Axons of these motor neurons travel in nerves to
muscle cells
• Axons of motor neurons branch profusely as they
enter muscles called axon terminal
• Each axon terminal forms a neuromuscular
junction with a single muscle fiber
• The motor end plate of a muscle, which is a specific
part of the sarcolemma that contains receptors and
helps form the neuromuscular junction
• Synaptic gutter or trough: the invaginated
membrane of muscle cell
• Synaptic cleft or synaptic space: the space b/w
axon terminal and fiber membrane
• Subneural clefts: at the bottom of gutter are
numerous folds of cell membrane to increase the
surface area at which neurotransmitter acts

5. AXON TERMINAL
• Numerous mitochondria which provide
energy for synthesis of neurotransmitter
which excite the muscle membrane
• Secretory vesicles store neurotransmitter
• Acetylcholine binds with receptors on
postsynaptic (motor end-plate) membrane
of muscle cell – activation of Na channel –
depolarization = End plate potential (graded
potential)
• when reaches a threshold action potential is
fired resulting in muscle contraction.

6. SUMMARY OF SEQUENCE OF EVENTS AT
NEUROMUSCULAR JUNCTION )
l i g a n d - g a t e d N a +
c h a n n e l
V o l t a g e - g a t e d
C a 2 + c h a n n e l
S y n a p t i c
v e s i c l e
P o s t s y n a p t i c
m e m b r a n e
A c e t y l c h o l i n e
S y n a p t i c c l e f t
A c t i o n p o t e n t i a l
C a 2 +
P r e s y n a p t i c
t e r m i n a l
N a +
A c e t y l c h o l i n e b o u n d
t o r e c e p t o r s i t e o p e n s
1
2
3
4

7. SYNTHESIS & DESTRUCTION OF ACETYLCHOLINE

8. 61
AGENTS &DISEASES THAT
ALTER THE FUNCTION OF
NEUROMUSCULAR
JUNCTION

9. Drugs that stimulate NMJ by acetylcholine like action
• Methacholin, carbachol, and nicotine small dose: not destroyed by
cholineestrase.
• Black widow spider venom: the venom of black widow spider exerts
its effect by triggering explosive release of Ach from the storage
vesicles, not only at Neuromuscular junction but all cholinergic sites.
All cholinergic sites undergoes prolonged depolarization so spasm of
muscles.
• The most harmful result is respiratory failure due to spasm
of respiratory muscles.
DRUGS THAT STIMULATE NMJ

10. Stimulate NMJ by inactivating acetylcholinesterase
• Drugs such as neostigmine and physostigmine inactivate the acetyl
cholinesterase reversibly in the synapse so that it no longer
hydrolyses acetylcholine so it accumulates leading to muscle spasm
and can cause death due to respiratory failure.
DRUGS THAT STIMULATE NMJ

11. Organophosphorus compounds
• Toxic agents are used in some pesticides and military nerve
gases
• Irreversibly inhibiting acetylcholinesterase
• Prevents the inactivation of released ACh.
• Spasm of diaphragm
• Respiratory failure
DRUGS THAT STIMULATE NMJ

12. DRUGS THAT BLOCK THE TRANSMISSION AT
NMJ
• Curare : curare competitively binds to Acetylcholine receptor sites
on motor end plate ,so Acetylcholine cannot combine with these sites
to open ion channels and muscles paralysis ensues .
• In severe poisoning person dies of respiratory failure

13. BOTULINUM TOXIN:
Botulinum toxin exerts its lethal effect by blocking the
release of Acetylcholine from the terminal button in
response to a motor neuron action potential .
• Clostridium botulinum poisoning most frequently result
from improperly canned food contaminated with
clostridia bacteria
• Death is due to respiratory failure caused by inability to
contract diaphragm .
66

14. THERAPEUTIC USE OF
BOTOX
• Botulinum toxin (Botox) is used by the
cosmetic surgeons to smoothen the
age related wrinkles.
• Wrinkles are formed by facial muscles
that have become over activated or
permanently contracted as a result of
years of performing certain repetitive
facial expressions
• So by relaxing these muscles it
temporarily smoothes out these age
related wrinkles.

15. DISEASE OF NMJ: MYASTHENIA GRAVIS
• A disease involving N.M junction is characterized by
the extreme muscular weakness
(myasthenia=muscular & gravis=severe)
• It is an auto immune condition in which the body
produces antibodies against its own motor end
plate acetylcholine receptors.
• Thus not all Acetylcholine molecules can find
functioning receptors site with which to bind.
• As a results ,Acetyl cholinesterase destroys much of
Acetylcholine before it ever has a chance to interact
with receptor site & contribute to End plate
potential.
• It is treated with long acting acetylcholinesterase
inhibitor pyridostigmine or neostigmine. Which
maintains the Ach levels at NMJ at high levels thus
prolonging the time available for Ach to activate its
receptors.
68

16. REGARDING ACETYLCHOLINE AT MOTOR
ENDPLATE THE FOLLOWING IS TRUE
a) Synthesized in post synaptic membrane
b) Stored in vesicles in presynaptic membrane
c) Enzyme for its synthesis is cholinesterase
d) Enzyme for its hydrolysis is choline acetylase

17. MUSCULAR SYSTEM

18. 1. Excitability
 the ability to receive and respond to stimuli for e.g. Can respond to chemical
neurotransmitters.
2. Contractility
 Contracts when it is excited
3. Extensibility
 The ability of muscles to be stretched
4. Elasticity
 The ability of muscle to resume a resting length after it has been stretched.
FUNCTIONAL CHARACTERISTICS OF MUSCLES

19. 1. Depending upon striations:
 Striated: e.g. cardiac muscle and skeletal muscle
 Non – striated: smooth muscle
2. Depending upon the control:
 Voluntary: Skeletal muscles
 Involuntary: Cardiac and smooth muscles
3. Depending upon situation:
 Cardiac: in heart
 Skeletal: attached to bones
 Smooth or visceral: present in viscera
CLASSIFICATIONOF MUSCLES

21. SKELETAL MUSCLE MICROSCOPIC STRUCTURE
• Composed of muscle cells (fibers),
• Fibers are long, cylindrical, and multinucleated
and abundant mitochondria
• Striated appearance. Nuclei are peripherally
located
• Cell membrane = sarcolemma. Cytoplasm =
sarcoplasm. SER = sarcoplasmic reticulum
 Each muscle fiber has several hundred to
several thousand myofibrils. (80% of cell
volume)
 Myofibrils are aligned to give distinct bands
 I band = light band & A band = dark band

23. A BAND (ANISOTROPIC TO POLARIZED LIGHT)
• With an electron microscope , a
myofibril displays alternating dark bands
(A band) and light band (I band) .
• A bands: a dark band; full length of thick
filament & the portions of thin
filaments that overlaps on both ends of
the thick filaments
• H zone - thick but NO thin filaments
• M line –system of supporting
proteins which hold the thick
filaments together vertically within
each stack (protein to which myosins
attach)

24. I BAND ( ISOTROPIC TO POLARIZED LIGHT)
• Having like properties in all directions
(singly refractive)
• I bands: a light band; it is made up of
the remaining part of actin filament on
the 2 adjoining sides of sarcomeres
• Only thin but NO thick filaments
• In the middle of I band is a Z line
• Z disk: filamentous network of protein.
Serves as attachment for actin filaments of
the two adjoining sarcomeres
• So I band extends from A band of one
sarcomere to A band of the next
sarcomere

25. TITIN
• Titin filaments: single strand of giant,
elastic protein called titin extend in
both direction from the M line along
the length of the thick filament to the
Z lines it is the largest protein in the
body with 30,000 amino acids
• It stabilizes the position of myosin
filament and increases muscle
elasticity

26. • The distance between two successive Z lines is called sarcomere
which is the functional unit of the skeletal muscle.
• Each relaxed sarcomere is 2.5 μm in width and consists of one
whole A band and half of each of the two I bands located on
either side.
SARCOMERE

27. MYOFIBRIL
• Each myofibril is composed of
contractile filaments: myosin
filaments and actin filaments
which are large polymerized
protein molecules made up of
polymerization of myosin and
actin protein molecules
respectively that are responsible
for the actual muscle contraction.

28. MOLECULAR CHARACTERISTICS OF THE
CONTRACTILE FILAMENTS

29. THE THICK OR MYOSIN FILAMENT
• Myosin forms the thick or myosin filament
• Each thick filament is formed by the polymerization of 200 or more
myosin molecules

30. A SINGLE MYOSIN MOLECULE
• It is a protein containing 2 identical
subunits , each shaped like a golf club.
• The tails or 2 heavy chains of myosin
molecules wound together to form a rod
portion lying parallel to the myosin
filament and two heads projecting out at
one end.

31. • The tails of the myosin molecules
bundled together to form the
body of myosin filament
heads of the molecules
while
hang
outward to the sides of the body
• Mirror image of each other
• Also part of the body of each
myosin molecule hangs to the side
along with the head thus providing
an arm

32. BINDING SITES
1. Actin binding site : Can bind to
active sites on the actin
molecules
2. ATP binding site which has
ATPase activity that breaks down
ATP,releasing energy.

33. ULTRASTRUCTURE OF THIN FILAMENTS
ACTIN FILAMENT
Thin filaments = actin filaments
 Composed of 3 proteins
• The backbone of thin filaments are
chiefly composed of the actin
• Each actin molecule is a helical
polymer of globular or spherical
subunits called G actin which are
linked to create the F actin filaments
• It contains the active sites to which
myosin cross bridge attach during
contraction
• Tropomyosin and troponin are
regulatory subunits bound to actin

34. TROPONIN COMPLEX
• TnI – bound to the actin fiber and is
inhibitory, by blocking the binding site
• TnT – bound to the tropomyosin fiber holding
it in place
• TnC – will bind to Ca++ ions
• When no Ca bound to troponin , it stabilizes
tropomyosin in its blocking position over
active sites of actin filament.
• But when Ca binds to troponin, the shape of
this protein is changed in such a way that
tropomyosin slips away from its blocking
position so now actin and myosin filament
can bind with each other and result in muscle
contraction.

35. • SR has Ca released channel called
ryanodine receptor & when
stimulated, calcium released into
sarcoplasm
• Depolarization of the T tubules causes
a conformational change in the
dihydropyridine receptor.
• This conformation opens the
ryanodine receptors (Ca release
channels) on the nearby SR and Ca is
released in the sarcoplasm and cause
muscle contraction

36. • Activation by nerve causes myosin
heads (cross bridges) to attach to
binding sites on the thin filament
• Myosin heads then bind to the next
site of the thin filament
• This continued action causes a sliding
of the actin filament along the myosin
filament.
• The result is that the muscle is
shortened (contracted)
CROSS BRIDGE
CYCLING

37. CROSS BRIDGE CYCLING

38. MUSCULAR SYSTEM

39. CHANGES FOLLOWING SKELETAL MUSCLE
STIMULATION
A. ELECTRICAL CHANGES
B. EXCITABILITY CHANGES
C. MECHANICAL CHANGES
D. METABOLIC CHANGES

40. A. ELECTRICAL CHANGES
– Excitation : electrical event
– Contraction : mechanical event
Mechanical event follows electrical event

41. • Electrical event in a skeletal muscle membrane
is exactly similar to nerve action potential
•Differences:
• Same duration = 2 msec
• RMP=-90 mv
• voltage difference = from -90 to +30 mV
• AP is conducted along the muscle fiber at
5 m/sec
• AP precedes contraction by about 2 msec.
ELECTRICAL CHANGES

42. B. EXCITABILITY CHANGES
• SK. m. Action potential has the same refratory periods as in nerve.
• AP precedes contraction by about 2 msec, that is equal to the latent period of muscle
contraction.
• AP precedes contraction by about 2 msec.
• So, by the time the muscle begins to contract , it has already regained its excitability.

43. MECHANICAL CHANGES
EXCITATION – CONTRACTION COUPLING
•Excitation-contraction (EC) coupling is the
physiological process of converting an electrical
stimulus into mechanical response.
•Electrical stimulus is an action potential
•Mechanical response is contraction

44. SUMMARY OF SEQUENCE OF EVENTS AT NEUROMUSCULAR
JUNCTION )
l i g a n d - g a t e d N a +
c h a n n e l
V o l t a g e - g a t e d
C a 2 + c h a n n e l
S y n a p t i c
v e s i c l e
P o s t s y n a p t i c
m e m b r a n e
A c e t y l c h o l i n e
S y n a p t i c c l e f t
A c t i o n p o t e n t i a l
C a 2 +
P r e s y n a p t i c
t e r m i n a l
N a +
A c e t y l c h o l i n e b o u n d
t o r e c e p t o r s i t e o p e n s
1
2
3
4

45. TRANSVERSE TUBULES
• These are invaginations of
sarcolemmal membrane deep
into the muscle fiber
• They carry the action potential
from the muscle membrane
deep into the muscle fiber
• T tubule make contact with the
terminal cisternae of the
sarcoplasmic reticulum and
contain voltage sensitive
dihydropyridine receptor

46. • SR is an elaborate, smooth
endoplasmic reticulum surrounding
each myofibril. It consists of 2 parts
• terminal cisternae on either side of
the T-tubules
• Longitudinal tubules
• A single T-tubule and the 2
terminal cisternae form a triad
• Ca is accumulated in the SR by Ca
ATPase pump in its membrane
when contraction is over
• Within the SR Ca is bound to
calsequestrin, a Ca binding protein
SARCOPLASMIC RETICULUM (SR)

47. • SR has Ca released channel called
ryanodine receptor & when
stimulated, calcium released into
sarcoplasm
• Depolarization of the T tubules causes
a conformational change in the
dihydropyridine receptor.
• This conformation opens the
ryanodine receptors (Ca release
channels) on the nearby SR and Ca is
released in the sarcoplasm and cause
muscle contraction

48. TROPONIN COMPLEX
• TnI – bound to the actin fiber and is
inhibitory, by blocking the binding site
• TnT – bound to the tropomyosin fiber holding
it in place
• TnC – will bind to Ca++ ions
• When no Ca bound to troponin , it stabilizes
tropomyosin in its blocking position over
active sites of actin filament.
• But when Ca binds to troponin, the shape of
this protein is changed in such a way that
tropomyosin slips away from its blocking
position so now actin and myosin filament
can bind with each other and result in muscle
contraction.

49. • Activation by nerve causes myosin
heads (cross bridges) to attach to
binding sites on the thin filament
• Myosin heads then bind to the next
site of the thin filament
• This continued action causes a sliding
of the actin filament along the myosin
filament.
• The result is that the muscle is
shortened (contracted)
CROSS BRIDGE
CYCLING

50. CROSS BRIDGE CYCLING

51. Summary –
Muscle Contraction & RELAXATION
1.Acetylcholine is released at
neuromuscular junction
2.AP is propagated along membrane
& down T-tubule
3.Ca released from SR via a voltage
gated Ca channel
4.Ca binds to Troponin-C -
conformation changes favor
tropomyosin opening actin myosin
binding sites.
5.myosin cross-bridges attach-detach
from actins... pulls actin filament
toward M-line.
6.Ca is removed by Ca-pump (uptake
by SR)
7.tropomyosin blocks actin sites and
muscle relaxes.

52. Actin filaments slide over myosin to shorten sarcomeres
Actin and myosin do not change in length
Shortening of sarcomeres responsible for skeletal muscle contraction
During relaxation, sarcomeres lengthen

53. MECHANISM OF MUSCLE
CONTRACTION
• The above micrographs show that the sarcomere gets
shorter when the muscle contracts
• The light (I) bands become shorter
• The dark bands (A) bands stay the same length
• The H zone shortens
Relaxed
muscle
Contracted
muscle
relaxed sarcomere
contracted sarcomere

54. Relaxation of the skeletal muscle
•When no stimulus Ca ions are pumped back into the
SR since non availability of Ca so no muscle
contraction and muscle relaxed
•ATP is needed for myosin head to release actin

55. RIGOR MORTIS
• Rigor mortis is the stiffening of
muscles once a person dies.
• ATP is needed for myosin head to
release actin; in absence of ATP,the
muscle is unable to detach.
• With the lack of oxygen and
circulation, ATP production quickly
stops.
• It takes ~ 48-60 hours for muscle
proteins to breakdown & for the
muscle to “relax”.

56. Summary –
Muscle Contraction & RELAXATION
1.Acetylcholine is released at
neuromuscular junction
2.AP is propagated along membrane
& down T-tubule
3.Ca released from SR via a voltage
gated Ca channel
4.Ca binds to Troponin-C -
conformation changes favor
tropomyosin opening actin myosin
binding sites.
5.myosin cross-bridges attach-detach
from actins... pulls actin filament
toward M-line.
6.Ca is removed by Ca-pump (uptake
by SR)
7.tropomyosin blocks actin sites and
muscle relaxes.

57. MUSCLE TWITCH
A muscle twitch is the response of
a muscle to a single, brief threshold
stimulus or response to a single
action potential.
It is too short or too weak to be
useful
E. g. blinking of the eye
There are three phases of muscle
twitch
Latent period
Period of contraction
Period of relaxation

58. TYPES OF CONTRACTION

59. • Isometric (same length)
• Muscle does not shorten
• Does not require much sliding of
filaments, but force is developed
• No external work done
as W = F X D
• Eg. Sitting, standing, maintaining
posture, pushing against the wall
• Isotonic (same tension)
• Muscle shortens
• Sliding of filaments occurs, load
is moved
• External work is done
• Eg. Walking, moving any part of
body

60. MUSCLE TWITCH
ALL OR NON LAW
• The muscle fiber contracts maximally or doesnot contract at all.
• A single skeletal muscle fiber obeys the all or non law provided that all other
conditions remain constant.

61. PHASES OF A MUSCLE TWITCH
 Latent period – first few msecafter
stimulus; excitation Contraction
coupling taking place
Period of contraction – muscle
tension develops; muscle shortens
Period of relaxation – Ca2+
reabsorbed; muscle tension goes to
zero
The entire contractile response to
a single AP last for about 100msec

62. FACTORS AFFECTING SKELETAL MUSCLE
CONTRACTION
1. TYPE OF MUSCLE FIBER
2. STIMULUS FACTORS
• STRENGHT OF STIMULUS
• FREGUENCY OF CONTRACTION
3. LENGTH-TENSION RELATIONSHIP
4. LOAD-VELOCITY RELATIONSHIP
5. MUSCLE FATIGUE

63. MAJOR TYPES OF MUSCLE FIBERS
• Every muscle of the body is composed of a mixture of fast and
slow fibers and other fibers gradated b/w these two extremes
• Two major types
• Slow-oxidative (type I) fibers (Slowly acting muscles but with
prolonged contraction are composed of mainly slow fibers
(soleus muscle)
• Fast-glycolytic (type II) fibers (Rapidly acting muscles are
composed of fast fibers mainly)

64. RED MUSCLE - TYPE I
SLOW OXIDATIVE TYPE
• RICH IN MYOGLOBIN  RED IN COLOR
• NUMEROUS MITOCHONDRIA
• DEPEND ON CELLULAR RESPIRATION
FOR ATP PRODUCTION
• RESISTANT TO FATIGUE
• SLOW CONTRACTION (SLOW-TWITCH
FIBERS)
• DOMINANT IN MUSCLES USED
FOR POSTURE
WHITE MUSCLE - TYPE II
FAST GLYCOLYTIC
• LOW IN MYOGLOBIN WHITISH IN COLOR
• FEW MITOCHONDRIA
• RICH IN GLYCOGEN AND DEPEND ON
GLYCOLYSIS FOR ATP PRODUCTION
• FATIGUE EASILY
• FAST CONTRACTION (FAST-TWITCH FIBERS)
• DOMINANT IN MUSCLES USED FOR RAPID
MOVEMENT

65. STIMULUS FACTORS
GRADING OF MUSCLE CONTRACTION

66. MOTOR UNIT
• Motor unit - all muscle cells
innervated by the same
motoneuron – they will contract at
the same time
• Motor units vary in size - mostly
mixture of motor units of different
sizes
large motor units >100 cells
(typically slow postural muscles)
small motor units about 10
cells (precise control fast acting
muscles – those moving the eye)

67. SUMMATION
Adding together individual twitch contractions to increase the
intensity of overall muscle contraction.
Summation occur in 2 ways:
1.By increasing the number of motor units contracting simultaneously
(multiple fiber summation or motor unit recruitment)
2.By increasing the frequency of contraction which can lead to
tetanization. (frequency summation)

68. Motor Unit Recruitment
For stronger & stronger contractions, more &more
motor units are recruited or stimulated to contract

69. STIMULUS INTENSITY AND
MUSCLE TENSION
Figure 9.16

70. SIZE PRINCIPLE
A concept known as the size principle,
allows for a gradation of muscle force
during weak contraction to occur in small
steps, which then become progressively
larger when greater amounts of force are
required.
Cause of size principle:
Smaller motor units are driven by small
motor nerve fibers and the small motor
units are more excitable than the larger
ones so they naturally are excited first.

71. FREQUENCY SUMMATION OR
TETANIZATION
• Tetanization:
• Occurs if muscle fiber is
stimulated so rapidly that
it does not have a chance
to relax between stimuli
• Contraction is usually
three to four times
stronger than a single
twitch
• Results from sustained
elevation of cytosolic
calcium

72. TREPPE (STAIR CASE PHENOMENON)

73. TETANY
• Medical sign, involuntary
contraction of muscles, due to
increased AP frequency
• Low calcium  neurons
depolarize easily
Tetanus
• Medical condition caused by
prolonged contraction of skeletal
muscles
• Wound – spores of bacteria
Clostridium Tetani enter –
germinate – produce neurotoxin
• Cause muscle spasm

75. LENGTH AND TENSION RELATIONSHIP
• EXTENT TO WHICH TENSION CAN BE
DEVELOPED IN A MUSCLE
• MUSCLES OPERATE WITH GREATEST ACTIVE
FORCE WHEN CLOSE TO RESTING LENGTH
2.5ΜM. WHEN
• Length of fiber at onset of
contraction
important
is a very
factor influencing
stretched
beyond this,
active force
or shortened
the maximum
generated
decreases

76. FATIGUE
•Decreased capacity to work and reduced
efficiency of performance
•Types:
• Psychological
• Depends on emotional state of individual
• Muscular
• Results from ATP depletion
• Synaptic or fatigue of NMJ
• Occurs in neuromuscular junction due to lack of
acetylcholine. In intact organism it is unlikely to be
the site of fatigue

77. CAUSES OF MUSCLE FATIGUE
Lack of oxygen causes ATP deficit
Lactic acid builds up from anaerobic glycolysis
A local increase in ADP and inorganic phosphate from
ATP breakdown which will interfere with cross bridge
cycling
Accumulation of ECF K+ when Na K pump cannot
transport K back into muscle so decrease in
membrane potential so decrease excitability
Depletion of glycogen energy reserves

78. METABOLIC CHANGES AFTER MUSCLE
STIMULATION
ENERGETIC OF MUSCLE CONTRACTION
•When the muscle contract against the load it
perform the work and the energy required to
perform the work is derived from the chemical
reaction in the muscle cells during contraction
 Most of the energy is required for:
1. Cross bridge cycling
2. Ca pump
3. Na K pump

79. ENERGY SOURCES FOR CONTRACTION
Muscle contraction depends on the energy supplied by the
ATP
Since ATP is the only source of energy that directly be
used for contractile activity to continue, so ATP must be
constantly supplied
Only limited stores of ATP are immediately available in
muscle tissue which produces muscle contraction for 1-2
seconds
 3 pathways supply additional ATP as needed during
muscle contraction

80. Skeletal Muscle Energy Metabolism
3 ways to form ATP in a Muscle fiber

81. IMPORTANCE OF
GLYCOLYSIS
• Glycolytic reaction can occur even in
the absence of oxygen so muscle
contraction can be sustained up to a
minute when oxygen delivery from
blood is not available
• Rate of formation of ATP by glycolysis
is 2.5 times faster as compared to
oxidative phosphorylation

82. CONSEQUENCES OF GLYCOLYSIS
Large amount of nutrient fuel is used giving less
amount of energy so glycolysis rapidly depletes the
storage pool of glycogen
Lactic acid production may cause pain and stiffness
in the muscle
So both factors play a role in the onset of muscle
fatigue

83. OXIDATIVE
PHOSPHORYLATION
 More than95% of all energy used by
muscles for sustained long term
contraction is derived from this source
 The food stuffs consumed during this
process are :
 Carbohydrates
 Fats
 Proteins
For long term maximal contraction
(period of hours) greatest energy
production from fats

84. OXYGEN SUPPLY AND
CELLULAR RESPIRATION
• The early phase of cellular respiration yields few molecules
of ATP,so muscle has a high requirement for oxygen, which
enables the complete breakdown of glucose in the
mitochondria
• Hemoglobin in RBCs carries oxygen to muscles
• The pigment myoglobin stores oxygen in muscle tissue

85. OXYGEN DEBT
• During rest or moderate activity, there is enough oxygen to support
aerobic respiration.
• Oxygen deficiency may develop during strenuous exercise, and lactic
acid accumulates as an end product of anaerobic respiration.
• Lactic acid diffuses out of muscle cells and is carried in the bloodstream to the liver.
• Oxygen debt refers to the amount of oxygen that liver cells require to
convert the accumulated lactic acid into glucose, plus the amount that
muscle cells need to resynthesize ATP and creatine phosphate to their
original concentrations.
• Repaying oxygen debt may take several hours.

86. SMOOTH MUSCLE OR PLAIN MUSCLE
Smooth muscle fibers - a fusiform
shape –
- a spindle-like shape with single
nucleus (wide in the middle and tapers
at both ends)
- small diameter and length of fibers
• Group of muscle cells are arranged in
sheets
• No striations
• Filaments do not form myofibrils
• Not arranged in sarcomere & banding
pattern as found in skeletal muscle

87. SMOOTH MUSCLE
• Cell has three types of filaments
arranged diagonally
• Have dense bodies containing same
protein found in Z lines
• Thick myosin filaments
• Longer than those in skeletal muscle
• Thin actin filaments
• Contain tropomyosin but lack troponin
• Filaments of intermediate size
• Do not directly participate in contraction
• Form part of cytoskeletal framework
that supports cell shape

88. TYPES OF SMOOTH MUSCLES
• Single unit smooth muscle (unitary
smooth muscle or visceral smooth
muscle)
• Mass of hundreds or thousands of
smooth muscle fibers that contract as
a single unit
• Arranged in sheets or bundles
• Fibers become excited and contract as
single unit
• Cells electrically linked by gap
junctions
• Can also be described as a functional
syncytium

89. SINGLE-UNIT SMOOTH MUSCLE
• it is myogenic (via ionic channel dynamics or special pacemakers cells
- interstitial cells of Cajal e.g. in the gastrointestinal tract)
• Self-excitable (does not require nervous stimulation for contraction)
• So don’t have constant RMP
• Their RMP fluctuates without any influence by factors external to the
cell
• Well suited for forming walls of distensible, hollow organs e.g. gut,
bile ducts, ureters , uterus , and blood vessels

90. MULTIUNIT SMOOTH MUSCLE
• Its properties are partway b/w skeletal
muscle & single unit smooth muscle
• Neurogenic (innervated by a single nerve
ending like skeletal muscle)
• Consists of multiple discrete units that
function independently of one another
• Units must be separately stimulated by
nerves to contract
• Found
• In muscle of eye that adjusts lens for
near or far vision(ciliary muscle)
• In iris of eye
• At base of hair follicles (pilo erector
muscle)

91. CONTRACTILE MECHANISM IN SMOOTH
MUSCLE
• Similarities to skeletal muscle:
Actin and myosin interact with each other
Contraction activated by Ca ions
ATP is degraded to ADP
Differences:
Physical organization
In excitation contraction coupling
Control of contraction by Ca ions
Duration of contraction
Amount of energy required

92. SMOOTH MUSCLE
DIFFERENCES IN PHYSICAL ORGANIZATION
• No T-tubules, SR is poorly developed
• So Calcium comes from 2 sources
Mainly from ECF
Some from sparse SR stores
• Excitation-contraction coupling-
• Calcium binds to calmodulin
• Causes phosphorylation of myosin light chain kinase

93. NO T-TUBULES
• Because the diameter of smooth muscle
cells are so small most of the Ca entering
from ECF can influence cross bridge
activity even in the central region of the
cell without requiring an elaborate T –
Tubule - Sarcoplasmic reticulum
mechanism
• Plasma membranes have pouch like
infoldings called caveoli . Ca2+ is
sequestered in the extracellular space
near the caveoli, allowing rapid influx
when channels are opened

94. Calcium Activation of Myosin Cross Bridge in Smooth Muscle

95. Role of calcium in contraction in smooth muscle and skeletal
muscle

96. RELAXATION OF SMOOTH MUSCLE
•It is brought about by removal of Ca
•They are actively pumped out across the plasma
membrane and also back in Sarcoplasmic
reticulum
•When no Ca myosin is dephosphorylated and
no longer can interact with actin relaxing the
muscle

97. Comparison of smooth and skeletal muscle
contraction
•Most skeletal muscle contract and relax
rapidly and most smooth muscle
contraction is prolonged tonic contraction
lasting for hours or days .
•What causes this differences?

98. 1) SLOW CYCLING OF MYOSIN CROSS BRIDGE
CYCLING
•The attachment of cross bridges to actin then
release from actin and reattachment for the next
cycle is much slower in smooth muscle than
skeletal muscle
•It is due to less ATPase activity of myosin cross
bridge than skeletal muscle

99. 2) ENERGY REQUIRED TO SUSTAIN MUSCLE
CONTRACTION
•Very less energy is required to sustain the same
tension of contraction in smooth muscle as in
skeletal muscle. It is due to slow attachment and
detachment cycling of cross bridges and
because one molecule of ATP is required for
each cycle regardless of its duration

100. 3) SLOWNESS OF ONSET OF CONTRACTION &
RELAXATION
•The duration of contraction is much prolong in
smooth muscle as compared to skeletal muscle
•It is 30 times as long as skeletal muscle
•The slow onset and prolong contraction is due to
slow cycling of myosin cross bridge cycle

101. 4) Force of muscle contraction
•The maximum force of contraction of
smooth muscle is greater than that of
skeletal muscle due to prolong attachment
of myosin cross bridges to the actin
filaments

102. Latch phenomenon for prolongedholding of smooth
muscle contractions
•“Latch Mechanism - prolonged holding in
smooth muscle
a.After contraction is initiated, less stimulus and
energy are needed to maintain the contraction
(Energy conservation)
b.Can maintain prolonged tonic contractions for
hours with little energy and little excitatory signal
from nerves or hormones

103. SMOOTH MUSCLE STIMULATION
•Smooth muscle responds to stimulation from a
number of different physiological systems.
1. Nerves
2. Hormones
3. Mechanical manipulation (stretch)
4. Self stimulation (Automaticity)

104. A COMPARISON OF THE PROPERTIES
OF SKELETAL, CARDIAC, AND
VISCERAL MUSCLE
Property
Skeletal
Muscle
Cardiac
Muscle
Smooth
Muscle
Striations? Yes Yes No
Relative Speed
of Contraction
Fast Intermediate Slow
Voluntary Control? Yes No No
Membrane
Refractory Period
Short Long
Nuclei per Cell Many Single Single
Control of
Contraction
Nerves
Beats
spontaneously
but modulated by
nerves
Nerves
Hormones
Stretch
Cells Connected by
Intercalated Discs or
Gap Junctions?
No Yes Yes

105. SMOOTH
MUSCLE
• eg. gut wall, bronchi, uterus
• Controlled by nerve supply (autonomic nerves)
or hormonal control

106. SMOOTH
MUSCLE
• Resting membrane potential may be about -55mV
• There are different types of action potentials
• Spikes
– Slow waves -
– Plateau waves -
duration 10-50 ms
voltage from -55 to 0 mV
similar to cardiac muscles
• Ca2+ influx is more important that Na+ influx

107. EFFECT OF SERUM
HYPOCALCAEMIA
• Concentration of calcium in ECF has a
profound effect on voltage level at which Na+
channels activated
• Hypocalcaemia causes hyperexcitability of the
membrane
• When there is a deficit of Ca2+ (50% below
normal) sodium channels open (activated) by a
small increase in the membrane potential from
its normal level
– Ca2+ ions binds to the Na+ channel and alters the
voltage sensor

108. EFFECT OF SERUM
HYPOCALCAEMIA
• Therefore membrane becomes hyperexcitable
• Sometimes discharging spontaneously
repetitively
– tetanyoccurs
• This is the reason for hypocalcaemia causing
tetany

109. CARPOPEDAL SPASMS

110. MEMBRANE
STABILISERS
• Membrane stabilisers (these decrease
excitability)
• Increased serum Ca++
– Hypocalcaemia causes membrane instability and
spontaneous activation of nerve membrane
– Reduced Ca level facilitates Na entry
– Spontaneous activation
• Decreased serum K+
• Local anaesthetics
• Acidosis
• Hypoxia

111. MEMBRANE
STABILISERS
• Membrane destabilisers (these increase
excitability)
•Decreased serum Ca++
•Increased serum K+
•Alkalosis