MUSCLE

1. PHYSIOLOGY OF
MUSCLE
1

2. Objectives
At the end of this lesson, students are expected to:
1.Define characteristics of muscle.
2.Enumerate functions of muscle.
3.List and compare the 3 types of muscle cells.
4.Describe physiologic anatomy of skeletal muscle cells
5.Discuss on contraction and relaxation processes of Skeletal
and Smooth muscles
6.Identify disorders related to skeletal muscle cell
2
2

3.  It is the fleshy organ of the body that converts potential
energy of food into mechanical energy.
 Human body contains over 400 skeletal muscles
 Accounts 40% of the total BW.
 Skeletal muscle alone makes up about 40% of body
weight in men and 32% in women, with smooth and
cardiac muscle making up another 10% of the total
weight.
Introduction
3

4. Muscle Functions
1. Produces Movement
 Movement of body parts
 Movement of blood throughout the body
 Movement of lymph through the lymphatic
vessels
 Movement of food through the GI tract
 Movement of bile out of the gallbladder and
into the digestive tract
 Movement of urine through the urinary tract
 Movement of semen through the male and
female reproductive tracts
 Movement of a newborn through the birth
canal
4

5. Muscle Functions
2. Maintenance of posture
 Muscle contraction is constantly
allowing us to remain upright.
 The muscles of your neck are
keeping your head up right now.
 As you stand, your leg muscles
keep you on two feet.
3. Thermogenesis
 Generation of heat. Occurs via
shivering – an involuntary
contraction of skeletal muscle.
5

6. Muscle Functions
4. Stabilization of
joints
 Muscles keep the
tendons that cross the
joint nice and firm
 This does a wonderful
job of maintaining the
integrity of the joint.
All the things muscles do fall under one of these 4 categories.
6

7. 1.Skeletal/voluntary muscles
Located attached to bones & moves skeleton
They are elongated, cylindrical and multinucleated cells,
They are striated muscle
They are voluntary muscle, controlled by somatic NS (SNS)
2. Cardiac muscle:
Muscle of the heart
They are striated, branched and mononucleated
They are involuntary, controlled by autonomous NS (ANS),
drugs and hormones
Have the property of autorhythmicity and syncytium
Types of muscles: 3 types
7

8. Cardiac Muscle
 Striated, involuntary muscle
 Found in walls of the heart
 Consists of branching chains
of stocky muscle cells.
 Uni- or binucleate.
 Has sarcomeres & T-tubules
 Cardiac muscle cells are
joined by structures called
intercalated discs – which
consist of desmosomes and
gap junctions.
Notice the branching and
the intercalated disc,
indicated by the blue arrow.
8

9. 3. Smooth muscles
 Located in the wall of hallow organs (GIT, blood vessels,
uterus, urinary bladder, Iris)
 They have non-striated appearance, mononucleated cells
 involuntary muscle, controlled by ANS, drugs and hormones
 Have the property of autorhythmicity and syncytium
Types of muscles: 3 types
9

10. Types of muscle ….
10

11. Types of muscles
11

12. Characteristics of muscle:
 Excitability: Responds to stimuli (e.g. nervous impulses)
 Stimulus could be: neurotransmitter, hormone, stretch,
pH
 Contractility: Able to shorten forcefully in length
 Extensibility: Stretches when pulled
 Elasticity: Tends to return to original shape & length after
contraction or extension
12

13. Structure of Skeletal Muscle
 A single skeletal muscle cell, known as a muscle fiber, is
relatively large, elongated, and cylinder-shaped.
 A skeletal muscle consists of a number of muscle fibers lying
parallel to each other and bundled together by connective tissue
 The fibers usually extend the entire length of the muscle.
13

14. Skeletal Muscle
• Each muscle fiber in most skeletal
muscles:
– Extends the entire length of the muscle.
– Innervated by only one nerve ending,
located near the middle of fiber.
– Supplied by an artery & drained by one
or more veins.
14

15. 14
Physiologic-anatomy of skeletal muscle
15

16. Physiologic-Anatomy of skeletal
muscle
15
16

17. Structure of skeletal muscles: Connective Tissue Covering
 Epimysium
 Surrounds entire muscle
 Perimysium
 Surrounds bundles of muscle fibers (fascicles)
 Endomysium
 Surrounds individual muscle fibers
17

18. Components of a muscle fiber
18

19. Skeletal Muscle…physiologic anatomy
• Sarcolemma: plasma membrane of muscle fiber
• Sarcoplasm: cytoplasm of muscle fiber
– Sarcosome: mitochondria of muscle fiber
– Glycogen granules: provide glucose for energy needs
– Sarcoplasmic reticulum (SR): ER of muscle fiber
 functions as calcium storage depot in muscle cells.
• Transverse tubules (T-tubules):
 Invaginations on sarcolemma that penetrate through the
cell 16
19

20. Myofibrils
• Rod like specialized contractile elements of muscle fiber
• Constitute 80% of volume of muscle fiber .
• Compose d of thick & thin myofilaments.
 ~ 1500 myosin filaments and 3000 actin filaments
• A single muscle fiber may contain
• About 16 billion thick and 32 billion thin filaments
20

21. Myofibrils…
21

22. Thick Myofilaments
• Thick myofilament is made of contractile proteins called
myosin
• Single thick filament is made of ~ 300 myosin
molecules
• Myosin protein’s tails are intertwined each other and
the heads form crossbridge.
• Each crossbridge has two important sites crucial for
contraction:
1. Actin-binding site
2. Myosin ATPase (ATP-splitting) site 19
22

23. Figure. Structure of myosin molecules and their organization within a thick filam
20ent.
23

24. Thin Myofilaments
• Thin filament is made of 3 different types of proteins:
– Actin, tropomyosin and troponin.
Actin:
• Primary structural proteins of the thin filament
• Each actin molecule has special binding site, for attachment
with myosin crossbridge called myosin binding site
Tropomyosin
• Threadlike proteins those cover myosin binding site of actin
blocking interaction b/n actin and myosin at rest. 21
24

25. Troponin
• Trio (triad=three) of protein complex
• Made of three polypeptide units:
 Troponin-C (C- Calcium) = can bind with Ca2+
 Troponin- T (T= tropomyosin) = binds to tropomyosin
 Troponin-I (I- inhibitory) = binds to actin
• When troponin is not bound to Ca2+
– This protein stabilizes Tropomyosin in its blocking position
over actin’s crossbridges binding sites 22
Thin Myofilaments…
25

26. Thin Myofilaments…
• When Ca2+ binds to troponin,
– Shape of this protein is changed
Tropomyosin slips away from its blocking position.
– Hence, actin and myosin can bind and interact at the cross
bridges, resulting in muscle contraction.
• Tropomyosin and troponin are called regulatory proteins
– Because of their role in covering (preventing contraction) or
exposing (permitting contraction) the binding sites for cross-
bridge interaction between actin and myosin. 23
26

27. Thin Myofilaments
27

28. Thin Myofilaments…
24
28

29. Relation of thick and thin
myofilaments
26
29

30. Structural proteins
Titin:
–filamentous proteins connecting myosin to Z disc
–the largest proteins, being made up of nearly 30,000 AA.
Functions of Titin:
–Stabilize the position of the thick filaments
–By acting like a spring, it helps a muscle to passively recoil to its
resting length.
Nebulin:
– An inelastic giant protein
– Lies alongside thin filaments and attaches to the Z disk.
– Helps align the actin filaments
27
30

31. Sarcomeres
• Each myofibril is made up of 1000’s of repeating individual
units known as sarcomeres
• Each sarcomere is an ordered arrangement of thick and thin
filaments. It has:
– regions of thin filaments by themselves
– a region of thick filaments by themselves
– regions of thick filaments and thin filaments overlapping.
31

32. Sarcomeres…
• Myosin and actin filaments partially interdigitated and cause
myofibrils to have alternate light and dark bands
• Light or I bands contain only actin filaments
• One I band is actually part of 2 sarcomeres at once.
• Dark bands , contain zone of overlapping and H Zone (only
myosin region), are called A bands.
• M line is at the middle of H zone that helps to hold
thick filaments to one another
32

33. • Z disk ( line ) passes crosswise across the myofibril attaching
myofibrils to one another all the way across muscle fiber.
Key
• A = anisotropic meaning not light
• I = isotropic , meaning light
• Z = German word Zwischenscheibe, means “between
disc.”
• H= German word Hensen’s disc, meaning “bright” or clear.
• M= German word Mittelmembran, meaning middle
Sarcomere…
33

34. Sarcomeres…
34

35. Sarcomeres…
35

36. Sarcomeres…
Titin structure:
36

37. Sarcotubular System = T-Tubules + SR
• Each muscle fiber has many T-tubules
– Typically each myofibril has branch of T-tubule encircling
it
at each A-I junction
• At each A-I junction, SR will expand and form dilated sac
called terminal cisterna.
• Each T-tubule will be flanked by a terminal cisterna.
– This forms a triad consisting of 2 terminal cisternae and
one T-tubule branch.
37

38. Sarco-tubular System…
38

39. Molecular basis of skeletal Muscle Contraction
“Sliding filament hypothesis”
• Discovered by Hanson & Huxley in 1955
• Is the theory that states inward sliding of the thin
filaments, on each side of a sarcomere , over the stationary
thick filaments toward the A band’s center
• As they slide inward, the thin filaments pull the Z lines to
which they are attached closer together,
• So the sarcomere shortens.
• As all the sarcomeres throughout the muscle fiber’s length
shorten simultaneously, the entire fiber shortens
39

40. Sliding filament hypothesis…
38
Figure. Sliding of the thin filaments over thick filaments
40

41. Sliding filament hypothesis…
39
Figure. Structural changes during muscle contraction
41

42. Sliding filament hypothesis…
40
42

43. Sliding Filaments…
• All sarcomeres in a fiber will contract together which contracts
the fiber itself.
• Number of fibers contracting will determine force of contraction
of whole muscle.
• Whole process of muscle contraction can have 4 steps:
Step 1. Excitation
Step 2. Excitation-contraction coupling
Step 3. Contraction
Step 4. Relaxation
41
43

44. 1. Excitation
• All cells have voltage difference across their plasma
membrane.
– Causes?????
• The value for Vm in inactive muscle cells is typically
between
–80 and –90 millivolts.
• Generally each muscle is served by one nerve
• With muscle, each axon will go its own way and eventually
branch into multiple small extensions called telodendria.
44

45. • Each telodendria ends in a bulbous swelling known as the synaptic
end bulb
• The site of interaction b/n a neuron and any other cell is known as a
synapse.
• The synapse b/n a neuron and a muscle is known as the
neuromuscular junction
• Minute space b/n synaptic end bulb & sarcolemma is called
synaptic cleft.
Excitation…
45

46. • Motor end plate: depression in sarcolemma at synaptic cleft
• The synaptic end bulb is filled with vesicles that contain the
neurotransmitter, acetylcholine
• Motor end plate is chock full of acetylcholine receptors (Ach-R).
Excitation…
46

47. Excitation…
Characteristics of neuromuscular junction
1. Transmission is unidirectional
2. There is a single NMJ per muscle fiber
3. The neurotransmitter is always acetylcholine (Ach)
4. The post junctional receptor is always nicotinic receptor
5. The effect of Ach on NR is always excitatory producing
EPSP/EPP
6. There is a synaptic delay (0.2 – 0.3 ms)
7. It is fatigable due to depletion of ATP and NT storage
46
47

48. NMJ
48
48

49. Excitation…
Factors affecting the NMJ:
NMJ an be affected by various factors
• Calcium level:
– Hypercalcemia inhibits membrane excitability
– Hypocalcaemia increases membrane excitability
• Hypoxia: inhibits membrane excitability
50
49

50. Excitation…
Factors affecting the NMJ…
3.Drugs:
I. Ach- release inhibitors: Botulin toxin extracted from
Clostridium botulinum- inhibits membrane excitability
II. Nicotinic receptor (cholinergic) blockers: d-tubocurarine, α-
cobratoxin - inhibits membrane excitability
III. Cholinergic stimulants: nicotine, metacholine, carbacholine
- increases membrane excitability
IV. Anti-cholinstrase drugs: Physiostegmin, neostegmin
- increases membrane excitability 51
50

51. Factors affecting the NMJ…
•Hemicholinium-3 (hemi-choline)--drug
– Blocks choline transporter protein on neuron cell
membrane
•Vesamicol (drug)
– Blocks acetylcholine transporter protein on the vesicle
•Succinylcholine --drug for general anesthesia
– Continuous stimulation of EPP then decrease
responsiveness of V. gated Na channel – no AP
•Tubocurarine (toxin)
– Blocks nicotinic receptors on motor end plate –paralyzing
muscles of the body 52
Excitation…
51

52. How Excitation Occurs?
1. Nerve signal arriving at synaptic end bulb will cause
– Ach-containing vesicles to undergo exocytosis.
2. Ach will diffuse across synaptic cleft & bind to Ach receptors
which are ligand-gated Na+ channels.
– Binding of Ach causes opening of Na+ channels.
3. Na+ will rush into cell:
– Making local cell interior more positive (depolarization) but
it is a local event (local potential)= EPP
52

53. 4. Adjacent to motor end plate, sarcolemma contains voltage-
gated ion channels(Na+ channels)
– In order for these channels to open,
– Vm must depolarize from its resting value of –90mV to
nearly –50mV,
– this is threshold potential.
– This local potential or end plate potential cause action
potential.
How Excitation Occurs ...
53

54. STEP1: Action Potential
 STEP 1: ACTION POTENTIAL reaches the muscle
cell membrane
– The action potential comes from the motor neuron,
which contacts the muscle at the Neuromuscular
Junction
– Acetylcholine is released, and the muscle membrane
in depolarized
54

55. STEP1: Action Potential
55

56. How Excitation Occurs…
• Degree of depolarization depends on amount of Na+ influx
• Na+ influx
depends on how many Na+ channels were opened by binding
ACh.
• If Vm fails to
depolarize to threshold, nothing will happen. – Vm
will soon return to normal & no muscle contraction
• If Vm does reach threshold, 2 types of voltage-gated ion
channels will open:
56

57. How Excitation Occurs…
• If Vm reaches threshold, fast Na+ channels open and Na+
rushes in causing the Vm to depolarize to +30mV.
• Depolarization stops when Na+ channels become inactivated.
• At this point, slow K+ channels have opened & K+ efflux occurs.
• This returns Vm back to its resting level. This is
repolarization.
57

58. 2. Excitation-Contraction Coupling
• It is the process by which depolarization of muscle fiber
initiates contraction.
• AP travels along sarcolemma going in both directions and
spread down the T- tubules .
• Since T-tubules are simply invaginations of the sarcolemma,
– AP will spread down them
• It is electromechanical mechanism
58

59. STEP2: Calcium is Released
STEP 2: the depolarization of the muscle cell
membrane causes calcium release
Depolarization spreads into membrane regions
called Transverse Tubules (Ttubules)
T-tubules contact the Sarcoplasmic Reticulum
The sarcoplasmic reticulum is a modified
endoplasmic reticulum that stores Ca2+ and
contains Ca2+ channels
Calcium is released from the sarcoplasmic
reticulum into the cytosol of the muscle cell
59

60. STEP3: Calcium Activates Troponin
STEP 3: Calcium activates troponin
 Troponin normally holds tropomyosin onto actin
Troponin responds to Ca2+ entry and releases from
tropomyosin and actin
60

61. STEP4: Tropomyosin moves out of the
way
 Tropomyosin is released from myosin binding sites,
freeing the actin
61

62. 3. Contraction
• Once actin’s myosin binding site is exposed,
– myosin will attach to actin.
– myosin has just hydrolyzed ATP into ADP and Pi –
– both molecules are still bound to the myosin.
– The ATP hydrolysis provides energy for “cocking” of myosin
head.
• Once myosin is bound to actin,
– myosin head will release the ADP and Pi which will cause it
change of conformation. 61
62

63. STEP5: Myosin binds to Actin
 Myosin heads bind to actin, forming a
CROSSBRIDGE
63

64. STEP6: Myosin moves actin
 Myosin heads move actin inward toward the M
 Line, a movement called the POWERSTROKE –
requires ATP
64

65. Contraction…
• A common analogy is climbing a rope hand over hand.
65

66. 4. Relaxation
• Ca2+ pumps in SR membrane work constantly to get calcium
out of sarcoplasm and back into SR.
• They are unable to do this as long as muscle is still binding
ACh.
• ACh is released by the motor neuron as long as it keeps
being
stimulated.
– ACh does not remain bound to Ach-R for very long.
• It quickly releases and either binds again or
• hydrolyzed by the enzyme acetyl cholinesterase
66

67. Relaxation…
• When the muscle ceases being stimulated,
– the calcium pumps “win” and sarcoplasmic [Ca2+] drops.
– Calcium stops being available for troponin and then
– tropomyosin shifts back into its inhibitory position.
• Muscle then
– returns back to its original length via elasticity of connective
tissue elements,
– And the contraction of antagonistic muscles
67

68. STEP7: Myosin releases actin
 Myosin detaches from actin and resets for the next
contraction
 Requires ATP
68

69. STEP8: Calcium is returned to SR
 Calcium pumps return calcium to SR to stop the
signal, reset calcium and prepare for next contraction
69

70. Mechanism of muscle contraction (Excitation-
contraction coupling)-summary
• The process by which depolarization initiates
• Contraction is called excitation contraction coupling.
• It has several steps as follow:
1. Action potential initiated & propagated along the motor nerve fibre
and arrives at the end feet.
2. Opening of VG-Ca-channels and influx of Ca2+ to trigger the release
of Ach.
3. Ach released by Ca-dependent exocytosis and diffuse through the
synaptic cleft and binds to NR on post junctional membrane. 73
70

71. Mechanism of muscle contraction…
4. Opening of ligand gated Na-channels and influx of Na+ to
produce EPP.
5. Spread of depolarization through the sarcolemma
6. Spread of depolarization through the T-tubules
7. Depolarization of T-tubules stimulate SR to release Ca2+ into
sarcoplasm
8. Ca2+ binds to troponin-C
9. Ca2+ and troponin-C combination detaches troponin-I from the
active sites of actin
74
71

72. Mechanism of muscle contraction…
10. The detachment of troponin-I from actin displaces
tropomyosin, uncovering the active sites of actin filaments.
11. When the active site of actin exposed, the heads of myosin
connect to them, making cross-bridges b/n myosin and actin.
12. The ATPase enzyme on the myosin heads hydrolyze ATP into
ADP + -P plus energy.
13. The released energy causes the movement of the head
(power
stroke) towards the centre.
14. The head of myosin is charged with a new molecule of ATP
and then detached from actin leading to relaxation.
75
72

73. Mechanism of muscle relaxation
It has the following steps
1.Following muscle contraction, Ca2+ is re-uptaken back into SR
by Ca-pump, this requires ATP.
2.Decreased Ca2+ in the sarcoplasm→ Ca2+ detaches from
troponin-C →Tropomyosin covers the active sites of actin.
3.Head of myosin charged with ATP, and detached from actin –
Therefore, muscle relaxation is an active process requiring
energy.
73

74. Importance of ATP
• Large amount of energy (ATP) is consumed during muscular
performance for the following activities:
– To move the head of myosin (power stroke)
– Active Ca2+ pump from sarcoplasm to SR
– For Na-K-pump in the membrane
– For muscle relaxation
74

75. Motor unit
• Composed of a group of muscle fibers that function together
and the somatic motor neuron that controls them
• When this neuron is stimulated, all the muscle fibers it
synapses upon will be stimulated and will contract as a unit
• The number of muscle fibers per motor unit may be as high
as several hundred or as few as four.
– The smaller the motor unit, the finer and more delicate the
movements.
– Extraocular muscles typically have small motor units while
large postural muscles have large motor units
78
75

76. Motor unit..
80
76

77. • Twitch → contractile response of a muscle to a single action
potential
A sub-threshold stimulus would not cause contraction because no
AP would be produced
•1 stimulation → 1 twitch
• The muscle quickly contracts and then relaxes
•A single muscle twitch produces only a very
small force, Thus incapable of doing anything
Muscle Twitch
77

78. Phases of muscle twitch
A. Latent phase
• Time between stimulus application and generation of tension
• Includes all the time required for
excitation, E-C coupling, and activation of muscle
proteins
• Myosin binding to actin active site
B. Contraction phase
• Beginning to end of muscle tension → myosin heads slide along
the actin filaments
78

79. C. Relaxation phase
• From peak tension to no tension
• Ca2+ moved back into the cisternae
• Tropomyosin moves back over actin
• Myosin head release actin and the filaments move back into
resting position
79

80. Twitch Contraction
48
82
80

81. measurement of a neuron’s AP, a muscle fiber’s AP, and the tension developed by that
musc8l3e fiber.
81

82. Strength of muscle contraction
• This depends on the
– number of muscle fibers contracting within a muscle
– extent of motor unit recruitment
– tension developed by each contracting fiber
• To prevent fatigue the body alternates motor unit activity, like
shift s at a factory, to give motor units that have been active
an opportunity to rest while others take over.
• Changing of the shift is carefully coordinated,
– so the sustained contraction is smooth rather than jerky.84
82

83. Factors determining Whole-muscle
tension
1. Frequency of stimulation
2. Length of the fiber at the onset of contraction
3. Extent of fatigue
4. Thickness of the fiber
83

84. 1. Frequency of stimulation…
• If the muscle fiber has completely relaxed before the next action
potential takes place, a second twitch of the same magnitude as
the first occurs (see Fig below) results in identical twitch
responses.
• If, however, the muscle fiber is stimulated a second time before it
has completely relaxed from the first twitch, a second action
potential causes a second contractile response, which is added
“piggyback” on top of the first twitch.
• The two twitches from the two action potentials add together,
or sum, to produce greater tension in the fiber than that
produced by a single action potential. This is called twitch
summation
84

85. 1. Frequency of stimulation…
• Twitch summation is possible only because the duration of
the action potential (1 to 2 msec) is much shorter than the
duration of the resulting twitch (100 msec)
• If the muscle fiber is stimulated so rapidly that it does not
have a chance to relax at all between stimuli, a smooth,
sustained contraction of maximal strength known as tetanus
occurs.
• A tetanic contraction is usually three to four times stronger
than a single twitch. (Don’t confuse this normal physiologic
tetanus with the disease tetanus
85

86. 86

87. 1. Frequency of stimulation…
• If the stimuli are of moderate frequency just below the
minimum tetanic frequency, and each stimulus falls in the
relaxation phase, the result is a series of contraction with
incomplete relaxation.
• This type of contraction is called clonic contraction, clonus
or incomplete tetanus
• Twitch summation results from a sustained elevation in
cytosolic calcium permitting greater cross-bridge cycling
and from increased time to stretch the series-elastic
component.
87

88. • There is an optimal muscle length at which maximal tension
can be developed.
• AT OPTIMAL LENGTH (lo) At lo, when maximum tension can be
developed (point A in ● Fig below), the thin filaments optimally
overlap the regions of the thick filaments from which the cross
bridges project.
• At this length, a maximal number of cross bridges and actin
molecules are accessible to each other for cyles of binding and
bending
• The central region of thick filaments, where the thin filaments do
not
overlap at lo, lacks cross bridges; only myosin tails are found here
90
88

89. 2. Length of the fiber at the onset of contraction…
89

90. Types of Contractions
• Contractions can be:
– Isometric
• Iso= same,
metr=measure
– Isotonic
• Iso=same, ton=tension
90

91. Isotonic Contraction
• It is the type of contraction with no change in muscle tension
• There is shortening of the total Length of the muscle
• Occurs when contraction moves an object of moderate Weight
• Work is done in this type of contraction
91

92. 70
Generates
movement
Concentric:
flexion
(muscle shortens)
Eccentric:
extension
94
Concentri
c: flexion
(muscle
shortens)
92

93. Isometric Contractions
 It is the type of contraction with out change in
Length
 Occurs when muscle contraction fails to move
heavy objects
 No work is done in this type of contraction
95
93

94. 71
No
movement
Maintains posture
Maintains objects
in
fixed position
96
94

95. Skeletal Muscle Metabolism and Fiber
Types
• Three different steps in the contraction–relaxation process
require ATP
1. Splitting of ATP by myosin ATPase provides the
energy for the power stroke of the cross bridge.
2. Binding of a fresh molecule of ATP to myosin lets the
bridge detach from the actin filament at the end of a power
stroke so that the cycle can be repeated.
– This ATP is later split to provide energy for the next stroke of
the cross bridge.
95

96. Skeletal Muscle Metabolism…
3. Active transport of Ca2+ back into the sarcoplasmic reticulum
during relaxation depends on energy derived from the
breakdown of ATP.
• At rest ATP is also utilized by sodium potassium pump to
maintain resting membrane potential
96

97. 97

98. Muscle fibers have alternate pathways for
forming ATP.
• Only limited stores of ATP are immediately available in muscle
tissue,
• But three pathways supply additional ATPase needed during
muscle contraction:
1. Transfer of a high-energy phosphate from creatine
phosphate to ADP
2. Oxidative phosphorylation and
3. Glycolysis
98

99. 99

100. 1. Creatine phosphate
• Creatine phosphate is the first energy storehouse tapped at
the onset of contractile activity
• Just as energy is released when the terminal phosphate bond
in ATP is split, similarly energy is released when the bond b/n
phosphate and creatine is broken.
• The energy released from the hydrolysis of creatine
phosphate, along with the phosphate, can be donated directly
to ADP to form ATP.
• This reaction is catalyzed by the muscle cell enzyme creatine
kinase
102
100

101. 2. Oxidative phosphorylation
• If the energy-dependent contractile activity is to continue
• takes place within the muscle mitochondria if sufficient O2 is
present.
• This pathway is fueled by glucose or fatty acids, depending on
the intensity and duration of the activity
• yield of 32 ATP molecules for each glucose but slow process.
• muscle cells can form enough ATP through oxidative
phosphorylation during light exercise (such as walking) to
moderate exertion such as jogging or swimming
101

102. 3. Glycolysis
• There are respiratory and cardiovascular limits to how much O2
can be delivered to a muscle.
– That is, the lungs and heart can pick up and deliver just so much
O2 to exercising muscles.
• Furthermore, in near-maximal contractions, the powerful
contraction compresses almost closed the blood vessels that
course through the muscle,
– severely limiting the O2 avail able to the muscle fibers.
102

103. 3. Glycolysis…
• Even when O2 is available, the relatively slow oxidative-
phosphorylation system may not be able to produce ATP
rapidly enough to meet the muscle’s needs during intense
activity.
• A skeletal muscle’s energy consumption may increase up to
100-fold when going from rest to high intensity exercise
• Glycolysis alone has two advantages over the oxidative
phosphorylation pathway:
1. Operates anaerobically
2. proceed more rapidly than oxidative phosphorylation.
105
103

104. 3. Glycolysis…
• Lactate production
– when the end product of an aerobic glycolysis, pyruvate,
cannot be further processed by the oxidative
phosphorylation pathway, it is converted to lactate.
– Lactate accumulation has been implicated in the muscle
soreness that occurs during the time that intense exercise is
actually taking place.
• The delayed-onset pain and stiff ness that begin the
day after unaccustomed muscular exertion, however, are
probably caused by reversible structural damage.
106
104

105. Muscle Fatigue
• Occurs when an exercising muscle can no longer respond
to stimulation.
• Physiological inability to contract
• Possible causes of muscle fatigue
– Local increase in ADP and Pi
– Accumulation of lactate
– Accumulation of extracellular K+
– Depletion of glycogen energy reserves
107
105

106. • Physiological inability to contract. Types:
– Psychological (central) fatigue
• Feeling of tiredness and a desire to stop
• Depends on emotional state of individual
– Muscular
• Depletion of glycogen energy reserve
– Synaptic
• Occurs in NMJ due to lack of acetylcholine
108
Muscle Fatigue…
106

107. • Refers to the fact that post-exercise breathing rate > resting
breathing rate.
• This excess oxygen intake serves many tasks:
– Replenish the oxygen stored by myoglobin and hemoglobin
– Convert remaining lactic acid back into glucose
– Used for aerobic metabolism to make ATP which is used to:
• Replenish the phosphagen system
• Replenish the glycogen stores
• Power the Na+/K+ pump so as to maintain RMP 109
Oxygen Debts
107

108. Types of Skeletal Muscle Fibers
• Based on major pathways used to form ATP and
fatigability,
– Oxidative fibers – use aerobic pathways
– Glycolytic fibers – use anaerobic glycolysis
• Muscle fibers are classified into 3 types as
– Type-I: Slow, fatigue-resistant, oxidative fibers.
– Type-II a: fast, fatigue-resistant, oxidative fibers.
– Type-IIx: fast, fatigable, glycolytic fibers. 110
108

109. Types of Skeletal Muscle
Fibers...
• Fast/glycolytic fibers have:
– Myosin with high ATPase activities
– High content of glycolytic enzymes
– Large storage of glycogen
– Little myoglobin contents
– Few mitochondria
• Slow oxidative fibers have:
– Myosin with low ATPase activities
– Numerous mitochondria
– High capacity of oxidative phosphorylation
– Rich in arterial blood supply, high BF
– Large amount of myoglobin contents
111
109

110. Characteristics of Skeletal Muscle Fibers
112
110

111. Smallest,
weakest,
slowest (slow-
twitch)
Red muscle:
lots of mito,
myo, & blood
Aerobic cellular
respiration 
113
74
111

112. Sustained
contractions
High fatigue
resistance
Maintains
posture,
Aerobic
endurance
activities (marathon
running)
114
75
112

113. sprinting 115
77
Aerobic &
anaerobic
respiration 
ATP (store
glycogen)
Moderate fatigue
resistance
Walking,
113

114. 116
78
Largest,
strongest, fast
twitch
High glycogen
storage
White muscle: less
mito, myo, blood
114

115. INFLUENCE OF
TESTOSTERONE
• Men’s muscle fibers are thicker, and accordingly, their
muscles are larger and stronger than those of women, even
without weight training,
– because of the actions of testosterone, a steroid hormone
secreted primarily in males.
• Testosterone promotes the synthesis and assembly of myosin
and actin.
• This fact has led some athletes, both males and females, to the
dangerous practice of taking this or closely related steroids to
increase their athletic performance. 117
115

116. Hypertrophy: Increase in size of a cell, tissue or an organ.
•Muscle hypertrophy occurs due to the synthesis of more
myofibrils and synthesis of larger myofibrils.
•Resulting from very forceful, repetitive muscular activity.
 More capillaries
 More mitochondria
Caused by:
 Strenuous exercise
 Steroid hormones such as testosterone
 stimulate muscle growth and hypertrophy
118
Muscular Adaptation
116

117. Muscular Adaptation…
• Atrophy : Reduction in size of a cell, tissue, or
organ
• In muscles, its often caused by disuse.
119
117

118. Muscular Disorders
• Rigor Mortis
– Upon death, muscle cells are unable to prevent Ca2+ entry.
• This allows myosin to bind to actin.
– Since there is no ATP made postmortem,
• the myosin cannot unbind and the body remains in a
state of muscular rigidity for almost the next couple
days.
• Cramp: prolonged spasm that causes muscle to become taut
and painful
• Fibrosis : Replacement of normal tissue with heavy fibrous
120
118

119. • Myasthenia Gravis:
– My=muscle, asthen=weakness, gravi=heavy
– Autoimmune disease where antibodies attack the ACh
receptors on neuromuscular junctions.
– Results in progressive weakening of skeletal muscles.
– Treated by Anticholinesterase agents such as
neostigmine
Inhibits AChE temporarily and
 Prolongs the action of ACh at the NMJ to initiate an
AP and subsequent contraction in the muscle fibe1
r21
Muscular Disorders…
119

120. Myasthenia Gravis
Muscular Disorders…
120

121. Eaton Lambert syndrome
–Auto immune destruction of Ca2+ channel on pre-SM
Organophosphate poisoning
–OPs are Chemicals that irreversibly inhibit AChE.
• Prevent the inactivation of ACh.
• Normally ACh rapidly hydrolyze in to inactive
fragments of
choline and acetic acid.
–Death occurs due to respiratory failure
• b/c the diaphragm cannot repolarize and return to
resting conditions, then contract again
Muscular Disorders…
121

122. Botulism:
•Caused by Clostridium botulinum found in improperly canned
food
•When the toxin of the bacteria is consumed,
– blocks release of Ach at the NMJ by inhibiting the action
of proteins (synaptobrevin & syntaxin) on presynaptic
membrane.
– It prevents muscles from responding to nerve impulses.
– Muscle contraction can not occur.
•Death is due to respiratory failure caused by inability to
contract the diaphragm(paralysis of the diaphragm)
124
Muscular Disorders…
122

123. Smooth muscle
• Involuntary, non-striated muscle tissue
• Occurs within almost every organ, forming sheets,
bundles,
• In Cardiovascular system:
– Smooth muscle in blood vessels regulates blood flow
through vital organs.
– Smooth muscle also helps regulate blood pressure.
123

124. Smooth muscle…
• Digestive systems:
– Rings of smooth muscle, called sphincters, regulate mov’t
along internal passageways.
– Smooth muscle lining passageways alternates contraction
and relaxation to propel matter through alimentary canal.
• Integumentary system:
– Regulates blood flow to the superficial dermis
– Allows for piloerection
124

125. Smooth muscle …
• Respiratory system
– Alters the diameter of the airways and changes the
resistance to airflow
• Urinary system
– Sphincters regulate the passage of urine
– Move urine into and out of the urinary bladder
125

126. Smooth muscle…
Reproductive system
Females
–Assists in mov’t of the egg (and of sperm) through the female
reproductive tract
–Plays a large role in childbirth
Males
–Allows for mov’t of sperm along reproductive tract
–Allows for secretion of non-cellular parts of semen
– Allows for erection and ejaculation. 128
126

127. Smooth muscle cells
• Are uninucleate: contain 1 centrally placed nucleus
• Lack T-tubules
• Have a scanty sarcoplasmic reticulum
• Smooth muscle tissue is innervated by the autonomic
nervous system
• Myosin and actin are present and crossbridges formation
powers contraction,
• but the thick and thin filaments do not have the strict
repeating arrangement like that found in skeletal muscle
127

128. • No Z discs, instead thin filaments are attached to protein
structures called dense bodies which attach to the
sarcolemma.
Smooth muscle cells
128

129. Types of Smooth Muscle
• Smooth muscle varies widely from organ to organ in terms of:
– Fiber arrangement
– Responsiveness to certain stimuli
• Broad types of smooth muscle:
– Single unit
– Multi unit
129

130. Single Unit Smooth Muscle
(SUSM)
• More common
• Cells contract as a unit b/c all connected by gap junctions.
• AP can propagate through neighboring muscle cells due to
gap junctions.
• Due to this property, SUSM bundles form a syncytium that
contracts in a coordinated fashion
– such as uterine muscles contraction during childbirth
• Commonly found in the walls of the digestive tract, urinary
bladder, and uterus
130

131. Single Unit Smooth Muscle
(SUSM)…
131

132. Characteristics of Single Unit
Smooth Muscles
• Innervated by an autonomic nerve fiber.
• SUSM is myogenic;
– it can contract regularly without input from a motor
neuron
• A few of the cells in a given SUSM unit may behave
– pacemaker cells, generating rhythmic action potentials
due to their intrinsic electrical activity.
132

133. Multi-Unit Smooth Muscle
• No gap junctions.
• Contraction of each fiber is independent of all the others.
• Responsible to neural & hormonal controls
• Less common and have no pacemaker cells
• It is neurogenic
– its contraction must be initiated by motor neuron.
• Found in
– large airways (lungs), large arteries, arrector pili,
internal eye muscles
135
133

134. Smooth Muscle Contraction
• Begins with opening of membrane channels.
• Channels may be ligand (NTs, hormones ), voltage, or
mechanically-gated (stretch).
• Channels will allow significant calcium entry from ECF. –
Smooth muscle has little SR.
• Ca2+ binds to regulatory molecule called calmodulin and
activates it.
• Activated calmodulin activates an enzyme called Myosin
Light Chain Kinase (MLCK).
134

135. Smooth Muscle Contraction…
• Activated MLCK will add a phosphate group to the myosin
of thick filament.
• This enables myosin to interact with actin.
• Tropomyosin is present but not blocking actin’s myosin
binding sites
• Troponin is absent
135

136. Smooth Muscle Contraction…
136

137. 137

138. • For smooth muscle to relax
– Ca++ ions must be removed from the intracellular fluids by a
calcium pump back into the
A. ECF, or
B. Into sarcoplasmic reticulum
– This pump is slow-acting
• Accounts for prolonged contraction 143
Smooth Muscle Relaxation
138

139. Smooth Muscle Relaxation
139

140. Cardiac Muscle
• Provides the motive power for blood circulation
• Striated, involuntary muscle
• Found in walls of the heart
• Consists of branching chains of stocky muscle cells.
• Uni- or binucleate.
• Has sarcomeres & T-tubules
• Are joined by structures called intercalated discs
– which consist of desmosomes and gap
junctions.
140

141. Cardiac Muscle…
141

142. Cardiac Muscle
Intercalated disc
142

143. Cardiac Muscle…
• Intercalated discs have 2 components.
– Gap junctions (which provide an electrical link between all
cardiac myocytes) and
– Desmosomes (which provide a mechanical link between
all cardiac myocytes).
• The electrical & mechanical connections created by the
intercalated discs allow the thousands of cardiac muscle cells
to behave as if they were one giant cell.
• Multiple cells that function as one entity are often referred to
as
a functional syncytium. 148
143

144. Cardiac Muscle…
144

145. Cardiac Muscle…
• All cardiac myocytes are not identical.
• 99% of cardiac wall is composed of the contractile cardiac
muscle cells.
– they generate the force that pumps blood through the
systemic and pulmonary circuits.
• 1% are the autorhythmic cells (pacemakers) of the heart.
• lack the elaborate sarcomeres & other contractile
machinery.
– specialized to generate action potential spontaneously
and
without nervous system input.
145

146. Cardiac muscle…
• Do not contract unless stimulated electrically by pacemaker
tissue
• Less abundant but larger size T tubules
• Less developed SR
– Smaller intracellular reserve of Ca++, cardiac muscle cells
need additional Ca from ECF for contraction
– 90% of calcium source for contraction is from SR and
10% is from ECF
146

147. Excitation-contraction coupling in cardiac
muscle
• Mechanism by which AP causes contraction of myocardium
• Calcium ions provide the link b/n electrical excitation &
muscle contraction
• Influx of Ca2+ from ECF during excitation (plateau) triggers
release of Ca2+ from SR.
• Free cytosolic Ca2+ activates contraction of myofilaments
(systole)
147

148. Excitation-contraction coupling in
cardiac muscle
• Relaxation (diastole) occurs as result of uptake of Ca2+ by SR &
extrusion of intracellular Ca2+ by Na+-Ca2+ exchange
• Sequences
– Auto-rhythmicity → Membrane depolarization →T-tubule
depolarization→ Release of Ca2+ from SR + from T-tubule
(ECF)→ Ca2+ activates contractile molecules →Sliding of
filaments→ Contraction
148

149. Excitation-contraction coupling:
cardiac muscle
149

150. 155
Fig: EC coupling and relaxation in cardiac muscle cells
Excitation-contraction coupling:
cardiac muscle…
150

151. Cardiac muscle syncytium
• B/c cardiac cells are joined by gap junctions, AP propagates
from cell to cell
• Muscle cells contract as unit ( syncytium)
• Atrial syncytium: All atrial cells excite and contract together
as a unit
• Ventricular syncytium: All ventricular cells excite and contract
together as a unit
151

152. Electromechanical Properties of Heart
• Heart continues to beat after full denervation b/c of intrinsic
properties it has:
A. Automaticity : start pacemaking
B. Conductivity: highly developed in PNW
C. Contractility: Atrial & ventricular muscles are specialized for
contraction
C. Refractoriness :
– Cardiac cell is unresponsive to further stimuli
– The AP of cardiac muscle has a prolonged refractory period
152

153. Electrical activity of cardiac cells…
• Ionic basis of cardiac AP is associated with changes in
– permeability of cell membrane to: Na+, K+, and Ca2+
• Ionic basis of myocardial AP has 5-phases.
ions.
 Phase-0: Rapid depolarization caused by rapid Na-
influx
 Phase-1: initial repolarization caused by fast K+ channel
opening
 Phase-2: plateau caused by Ca2+ influx
 Phase-3: rapid Repolarization caused by slow
potassium
channel opening K+ efflux
 Phase-4: resting state
• RMP is re-established by Na-K-ATPase.
NB- RMP = -90 mv 158
153

154. 154

155. 161
Comparison of 3 muscle types
155