Skeletal muscle fibers can be classified into different types based on their contractile and metabolic properties; slow-twitch fibers (type I) are resistant to fatigue and rely more on aerobic metabolism, while fast-twitch fibers (type II) fatigued more quickly and can rely more on anaerobic metabolism; the distribution and recruitment of different fiber types allows for a gradation of force during muscle contractions ranging from low-force sustained contractions to brief high-force bursts.

1. Lec # 2
Skeletal Muscle Contraction-1
Date: 17th January, 2012
Time : 9-00 AM – 10-00 AM

2. Objectives..
1. explain the process of muscle
contraction & relaxation
• Mechanism of
muscle 2. explain the characteristics of
contraction & muscle contraction-muscle
relaxation twitch, graded response,
summation, clonus, tetanus &
fatigue and associate them to
• Characteristics real conditions in health &
of whole muscle disease
contraction
3. explain the length- tension
relationship in whole muscle
• Remodelling of
muscle to match 4. describe remodelling of muscle to
function match function

3. 1. Muscle cells are excited by somatic
efferent neurons.
2. Muscle cell excitation (the muscle
cell action potential) triggers muscle
cell activity (contraction).
3. Calcium (Ca++) is the second
messenger that links excitation to
contraction

5. Excitation-Contraction
Coupling
A term coined in 1952 to describe the
physiological process of converting an electrical
stimulus to a mechanical response
This process is fundamental to muscle
physiology, whereby the electrical stimulus is
usually an action potential and the mechanical
response is contraction.
EC coupling can be dysregulated in
many disease conditions.

6. TRIAD
MITOCHONDRIA
TERMINAL T- TUBULE
CISTERNAE
THIN
MYOFILAMENT
THICK
MYOFILAMENT
MYO
FIBRIL Z M Z

7. Neuromuscular
Transmission
T-tubules
DIHYDROPYRIDINE RECEPTORS
Voltage dependent Ca+2 channels
In humans, the gene encoding RyR1 SR
is located on chromosome 19q13.2 RYANODINE RECEPTORS[RyR1]
and spans 104 exons.
Voltage dependent Ca+2 channels
Opening
Ca2+ released from the
sarcoplasmic reticulum binds causes flow of Ca2+ from the
sarcoplasmic reticulum, after its
to Troponin C on actin filaments, release from the Calsequestrin,
into the cytoplasm.

10. • Mutations in the RYR1 gene underlie
several debilitating and/or life-threatening
muscle diseases including
– malignant hyperthermia (MH) ,
– heat/exercise induced exertional
rhabdomyolysis ,
– atypical periodic paralyses (APP)

11. Nebulin
Dystrophin
Proteins Titin Desmin
Alpha- Vimentin
actinin
• Structural
proteins
• Regulatory
proteins
• Contractile
proteins

17. 1 - Calcium released from sarcoplasmic
reticulum
2 - Myosin head energized via myosin-
ATPase activity which converts the
bound ATP to ADP + Pi
3 - Calcium binds to troponin
4 - Tropomyosin translocates to
uncover the cross-bridge binding sites

18. 5 - The energized myosin binding sites
approach the binding sites
6 - The first myosin head binds to actin
7 - The bound myosin head releases
ADP + Pi, flips and the muscle shortens
8 - The second myosin head binds to
actin

19. 9 - The first myosin head binds ATP to allow
the actin and myosin to unbind
10 - The second myosin head releases its ADP
+ Pi, flips & the muscle shortens further
11 - The second myosin head binds to ATP to
allow the actin and myosin to unbind
12 - The second myosin head unbinds from the
actin, flips back and is ready for the next
cycle

20. 13 - The cross-bridge cycle is
terminated by the loss of calcium from
the troponin
14 - Tropomyosin translocates to cover
the cross-bridge binding sites
15 - The calcium returns to the
sarcoplasmic reticulum, the muscle
relaxes & returns to the resting state

21. As a muscle
shortens, the
following is
observed:
a) sarcomeres
shorten;
b) A band length
remains constant
c) I band length
becomes shorten
d) myofilament
lengths remain
constant

22. SOME FACTS……….
• A single cycle of attachment, swivel,
and detachment of the myosin head will
produce a linear translation of the
myofilaments of about 10 nm.
• If all cross-bridges in a myofibril cycle
once synchronously, a relative movement
equal to about 1% of the muscle length will
occur, but obviously muscles shorten by
more than 1%.

23. • The total shortening of a sarcomere
during contraction may exceed 1,000 nm;
therefore the relative movement of a thin
and thick filament would be half this
amount or 500 nm.
• To achieve this magnitude of change in
total length when each cross-bridge cycle
produces a 10-nm shortening, a minimum
of 50 cycles must occur.

24. • The flexor muscles of the human upper
arm can contract at the rate of 8 m/sec
(Wilkie DR: J Physiol (Lond) 110:249-280,
1949), during which they can shorten by
as much as 10 cm. This contraction rate
gives a contraction rate for the sarcomere
of 160 nm/msec. If a stroke of the cross-
bridge is taken to be 10 nm, then at this
rate there will be a minimum of 16
strokes/msec. Thus, the swivel time for the
cross-bridge must be of the order of 60
sec.

25. • In any case, it is clear that the swiveling
of the cross-bridge must be a fast
mechanical process.
• The cross-bridge theory says that sliding
is produced by physical attachment of
myosin heads to actin and by rotation
of the heads.

26. • Tension is developed by physical bonds
between thick and thin filaments.
• Tension depends upon the degree of
overlap between thick and thin filaments.
• The cross-bridge originates at the thick
filament and terminates at the thin
filament.

27. Malignant Hyperthermia
• MH is an autosomal dominant disease in which
genetically susceptible individuals respond to
inhalation anesthetics (e.g., halothane) and
muscle relaxants (e.g., succinylcholine) with
sustained muscle contractions.
• More than 150 different point mutations in the
RYR1 gene have been identified and linked to
MH .
• The majority of RyR1 mutations linked to MH
cluster in the cytoplasmic domains of RyR1
(amino acids 35 to 614 and 2129 to 2458).
• Another cluster of mutations is found near the
carboxyl terminus (4637 to 4973)

28. • MH is often a silent disorder that goes
undetected until the patient undergoes
surgery or is exposed to high ambient
temperatures (∼37° . The underlying
C)
physiological consequence of MH is abnormal
calcium homeostasis with increase sensitivity of
channel opening in response to activators .
• An MH episode is characterized by elevations in
body temperature, metabolic acidosis, hypoxia,
tachycardia, skeletal muscle rigidity, and
rhabdomyolysis and is life threatening if not
immediately treated with dantrolene

29. • HEAT RIGOR
• RIGOR MORTIS
http://cshperspectives.cshlp.org/content/2/11/a003996.full.pdf+html

30. Factors that Affect the Efficiency
of Muscle Contraction

31. Tension and Load
The force exerted on an object by a
contracting muscle is known as tension.
The force exerted on the muscle by an
object (usually its weight) is termed
load.
According to the time of effect exerted
by the loads on the muscle contraction
the load was divided into two forms,
preload and afterload.

32. Preload
Preload is a load on the muscle before
muscle contraction.
Determines the initial length of the muscle
before contraction.
Initial length is the length of the muscle
fiber before its contraction.
It is positively proportional to the preload.

33. Afterload
Afterload is a load on the muscle after the
beginning of muscle contraction.
The reverse force that oppose the contractile
force caused by muscle contraction.
The afterload does not change the initial
length of the muscle,
But it can prevent muscle from shortening
because a part of force developed by
contraction is used to overcome the afterload.

34. The Effect of Sarcomere Length on Tension
The Length – Tension Curve
Concept of optimal length

35. Types of Contractions I
Twitch: a brief mechanical contraction
of a single fiber produced by a single
action potential at low frequency
stimulation is known as single twitch.
Tetanus: It means a summation of
twitches that occurs at high frequency
stimulation

36. Effects of Repeated Stimulations
Figure 10.15

37. 1/sec 5/sec 10/sec 50/sec

38. Types of Contractions (II)
Afterload on muscle is resistance
Isometric
Length of muscle remains constant. Peak tension
produced. Does not involve movement
Isotonic
Length of muscle changes. Tension fairly constant.
Involves movement at joints
Resistance and speed of contraction inversely
related

39. Isotonic and Isometric Contractions

40. LECTURE# 3
MUSCLE CONTRACTION-2
DATE: 17TH JANUARY,2012
Time : 10-30 AM to 11-30 AM
Venue- LT @ level 1
Sarmishtha Ghosh
essjee63@gmail.com

41. LEARNING OBJECTIVES
Whole body contractions
Muscle fiber types
Muscle Tone- definition, basis and
importance in posture
Applied terms: atrophy,
hypertrophy,hypotonia, hypertonia,
denervation hypersensitivity
ALSO MAKE SURE YOU ARE AWARE OF
HYPOCALCEMIC TETANY
TETANUS
MALIGNANT HYPERTHERMIA

42. Skeletal muscle Specialized
contractile
elements, 80%
of the muscle
fiber,
Dm= 1µm
40% of the ,L=2.5 ft Highly
organized
body weight cytoskeletal
elements
Single muscle cell SINGLE
: multiple nuclei
Abundant Large,
mitochondria elongated
cylinder shaped
Dm= 10-100 µm
L=2.5 ft

43. Muscle is a chemomechanical
transducer.
It has the ability to convert chemical energy,
stored in the terminal phosphate group of ATP,
into mechanical work.
• The myosin crossbridge, or myosin molecular
motor, is the site for this energy conversion.
• Thus in addition to generating force and
shortening, myosin is an enzyme that
hydrolyzes ATP (i.e. ATPase).

44. Muscle metabolism-
production of energy
Three ways • Short duration
Creatine-Phosphate
exercises system
– From Creatine – Sprint <= 10
Phosphate sec.
– By Anerobic Anerobic
Cellular • Activities lasting pyruvate- lactate
Respiration < 10 mins system
– By Aerobic
Cellular • Activities lasting
Respiration > 10 mins Aerobic
system

45. IN THE BODY…..
• GROUPS OF MUSCLE FIBERS ARE
ORGANIZED AS WHOLE MUSCLES
• BUNDLED TOGETHER AND ATTACHED
TO BONES
• TENDONS- tough collagenous structures
CONNECT MUSCLES TO BONES
• MUSCLES, BONES & TENDONS
– SERVE AS A UNIT

46. SKELETAL MUSCLE
MECHANICS

47. • Contraction of whole muscles can be of varying
strength
– Number of muscle fibers contracting within a
muscle
• Motor units and their recruitment
– Tension developed by each contracting fiber
• Frequency of stimulation
• Length of fiber at onset of contraction
• Extent of fatigue
• Thickness of fiber

48. • When a weak signal is sent by the CNS to
contract a muscle,
– the smaller motor units, being more excitable than
the larger ones, are stimulated first.
• As the strength of the signal increases,
– more motor units are excited in addition to larger
ones, with the largest motor units having as much as
50 times the contractile strength as the smaller ones.
– As more and larger motor units are activated, the
force of muscle contraction becomes
progressively stronger.
• 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.

50. Classification of voluntary
muscular contractions
• Voluntary muscular contractions can be classified according to either length changes
or force levels.
• In concentric contraction, the force generated is sufficient to overcome the resistance,
and the muscle shortens as it contracts. This is what most people think of as a
muscle contraction.
• In eccentric contraction, the force generated is insufficient to overcome the external
load on the muscle and the muscle fibers lengthen as they contract. An eccentric
contraction is used as a means of decelerating a body part or object, or lowering a
load gently rather than letting it drop.
• In isometric contraction, the muscle remains the same length. An example would be
holding an object up without moving it; the muscular force precisely matches the load,
and no movement results.
• In isotonic contraction, the tension in the muscle remains constant despite a change
in muscle length. This can occur only when a muscle's maximal force of contraction
exceeds the total load on the muscle.
• In isovelocity contraction, the muscle contraction velocity remains constant, while
force is allowed to vary. True isovelocity contractions are rare in the body, and are
primarily an analysis method used in experiments on isolated muscles which have
been dissected out of the organism.

51. Types of Contraction
• ISOTONIC
– Muscle tension remains constant while muscle changes length
– Body movements, moving external objects
• ISOMETRIC
– Length remains same while tension increases
– Lifting objects heavier than one’s capacity
• Shift between isometric and isotonic contractions
YOU PICK UP A BOOK TO READ
Lifting the book – biceps : isotonic contraction
Hold the book in front of you : isometric
contraction

52. ISOTONIC
CONCENTRIC ECCENTRIC
TENSION REMAINS SAME TENSION REMAINS SAME
LENGTH SHORTENS LENGTH INCREASES
LOWERING THE LOAD
TO THE GROUND

53. OTHERS…….
• Not limited to pure
Isotonic & pure
Isometric
Contractions
• Muscle length & Stretch the Bow
tension can vary Tension of Biceps
throughout a range continuously increases,
of motion Bow is drawn further back
Length shortens
simultaneously

54. Still More…..
• Muscles of tongue
– Not attached at the free end
– Isotonic contractions :
facilitate speech and eating
• External eye muscles
– Skull @ origin, eye @
insertion
– Isotonic : Eye movements
• Sphincters :
– Unattached to bone
– Actually prevents movement
– Prevents exit of urine and
feces by isotonic contraction

55. • Velocity of shortening is related to the load
• Greater the load, lower is the velocity
• Muscles do work in physical sense when it
moves an object
Work= Force x Distance
Muscle tension reqd Through which the
To overcome Object is moved
The weight of object
To be moved
Isometric: Isotonic:
no object is moved object is moved
Mechanical Mechanical
Efficiency=0 Efficiency=25%
Maintain
Body Temperature Heat=100% Heat= 75%

56. TYPES OF SKELETAL MUSCLE
FIBERS
• SLOW OXIDATIVE TYPE- I
• FAST OXIDATIVE- TYPE-IIa
GLYCOLYTIC
• FAST GLYCOLYTIC TYPE- IIb

57. Characteristics
• Myosin ATPase activity
• Speed of contraction
• Resistance to fatigue
• Capacity for oxidative phosphorylation
• Enzymes for Anerobic Glycolysis
• Mitochondria
• Capillaries
• Myoglobin content
• Glycogen content
• Content of Sarcoplasmic Reticulum
• Fiber diameter
• Color of fiber

58. Type I fibers -also called slow
oxidative (SO) fibers
Postural
muscles

59. Type IIa or fast oxidative-glycolytic
(FOG) :a hybrid of FG and SO fibers

60. Type IIb: fast-twitch glycolytic fibers, also called
FG or : most common fast-twitch fibers in
humans [ white fibers]

61. SKELETAL MUSCLE
FIBERS
SLOW FIBERS FAST FIBERS
PROLONGED TENSION RAPID TENSION
GENERATOR GENERATOR
Large fCSA
Small fCSA
High inn. ratio
Low inn. ratio Can generate small Can generate larger
forces@ low metabolic forces@ high metabolic
cost cost
Aerobic +
Mitochondria Anerobic
Fatigue
Myoglobin Fatigability
Resistant
Intermediate- Low
Tonic Slow twitch
multiterminal Single terminal 2A 2B 2X
Extraocular m. Postural m. Arm muscles/ other sites.

62. • Majority of muscles are of mixed fiber type
composition being a combination of fast and
slow fibers occurring in two arrangements
– 1) mosaic - fast and slow fibers uniformly
distributed
– 2) compartmentalized - fiber types non-
uniformly distributed into intramuscular
compartments
• Some muscles which are used for repetitive or
constant tasks (e.g., posture) can be comprised
nearly entirely of slow fibers
– - e.g., soleus

63. • Genetic Endowment of muscle fiber types
• Adaptation to demands placed on them
– Changes in their ATP synthesizing machinery
– Changes in their diameter

64. • Anerobic, short duration,high intensity
resistance training
– Weight lifting
– Muscle enlargement
• Actual increase in diameter of fast glycolytic fibers
• Increased synthesis of Actin and Myosin filaments
– Hypertrophy –
• Actions of Testosterone – the male sex
hormone
• Interconversion between fast muscle fiber
types
– No conversion between fast and slow fibers
• Limited repair system available
– No mitosis
– Some myoblasts may fuse and cause a muscle fiber
– Extensive injury- not adequate

65. MUSCLE INJURY & REPAIR
Triggers a sequence of events that begin with
a host inflammatory response that is followed by muscle fiber
regeneration and new collagen synthesis.
The inflammatory response involves at least three types of cells,
including neutrophils,
ED1+ macrophages, and
ED2+ macrophages.
Growth factors and cytokines appear to play a role in the inflammatory process
and repair of the damaged tissue..
Satellite cells play an integral role in normal development of skeletal muscle by
providing a source for postmitotic myonuclei. In addition, the satellite cell is
essential to the repair of injured muscle by serving as a source of
myoblasts for fiber regeneration
At the same time muscle fiber regeneration is occurring, there is expression of types I and
III collagen that under certain circumstances can lead to scarring and fibrosis.

66. HEPATOCYTE
GROWTH FACTOR
CAVEOLIN-1
EXPRESSION
DOWN REGULATED

67. skeletal-muscle pump
• The is the pumping effect of skeletal muscle on
veins to increase blood flow. During exercise,
muscles squeeze veins, effectively pumping
blood back to the heart. This is a significant
factor affecting venous return which is the
amount of blood that returns to the heart via the
veins.
• Skeletal muscle surrounding a vein is relaxed,
– the upper and lower vein valves are closed
– backflow of the blood inside the vein prevented

68. MUSCLE TONE
• Residual muscle tension or tonus
• is the continuous and passive
partial contraction of the muscles.
• helps maintain posture, and it declines
during REM sleep.

69. • Unconscious nerve impulses maintain the muscles in a
partially contracted state. If a sudden pull or stretch
occurs, the body responds by automatically increasing the
muscle's tension, a reflex which helps guard against
danger as well as helping to maintain balance.
• The presence of near-continuous innervation makes it
clear that tonus describes a "default" or "steady state"
condition. There is, for the most part, no actual "rest state"
insofar as activation is concerned.
• In terms of skeletal muscle, both
the extensor and flexor muscles, under
normal innervation, maintain a constant tone while "at
rest" that maintains a normal posture.

70. Pathological tonus
• Physical disorders can result in
– abnormally low (hypotonia) or
– high (hypertonia) muscle tone.
• Another form of hypertonia is paratonia, which is
associated with dementia. Hypotonia is caused by lower
motor neuron disease like poliomyelitis. Hypertonia is
caused in upper motor neuron disease like lesion in
pyramidal tract and extrapyramidal tract. Hypertonia can
be of clasp knife variety, in which there is increased
resistance only at the beginning or at the end of the
movement, or lead pipe variety, in which there is
resistance throughout to passive movement, or it may be
of cog wheel type, in which the resistance to passive
movement is in jerky manner.
•

71. http://faculty.pasadena.edu

74. alpha-gamma
coactivation;
when we actively contract
extrafusal fibers (muscle),
the contractile portion of
intrafusal fibers contract
as well; this stretches the
spindles causing them to
fire. Alpha motor neurons
fire to contract extrafusal
fibers and gamma motor
neurons are
COACTIVATED to fire
with alpha's to contract
intrafusal fibers
simultaneousely

78. Activation of
Stretching of muscles Sensory Neuron
Stimulation of
MUSCLE SPINDLE
MUSCLE
OPPOSES
Information
Processing
Contraction
At
Of
Activation of Motor neuron
Muscle
Motor neuron
extrafusal
fibers, rich in
contractile
proteins,

79. TERMS……..
• ATROPHY HYPOTONIA
• HYPERTROPHY HYPERTONIA
• HYPERPLASIA ATONIA
RIGOR MORTIS
TETANUS
TETANY

80. DENERVATION HYPERSENSITIVITY
• Innervated adult skeletal muscle is sensitive to acetylcholine at the
end-plate region only. After denervation the entire muscle
membrane becomes chemosensitive..
• The motor nerve to skeletal muscle is cut and allowed to degenerate
--------the muscle gradually becomes extremely sensitive to
acetylcholine.
• This denervation hypersensitivity or supersensitivity is also seen
in smooth muscle. Smooth muscle, unlike skeletal muscle, does not
atrophy when denervated, but it becomes hyperresponsive to the
chemical mediator that normally activates it
• It appears that the new receptors are released into the muscle
surface from post-Golgi vesicles, giving rise to local ‘hot spots’ in A
Ch sensitivity. Their generation appears to be triggered by the
absence of a neural factor controlling genetic expression in the
muscle cell — this factor may be A Ch itself.

81. ELECTROMYOGRAM
• Diagnose conditions that damage
muscle tissue, nerves, or the
junctions between nerve and
muscle (neuromuscular junctions),
for example, a herniated disc.
• Evaluate the cause of weakness,
paralysis, involuntary muscle
twitching, or other symptoms.
• Problems in a muscle, the nerves
supplying a muscle, the spinal
cord, or the area of the brain that
controls a muscle can all cause
these kinds of symptoms.

82. • Nerve conduction velocity is often used
along with an EMG to differentiate a
nerve disorder from a muscle disorder.
• NCV detects a problem with the nerve
whereas an EMG detects whether the
muscle is functioning properly in
response to the nerve's stimulus.
• Nerve conduction studies are done to…
– Detect and evaluate damage to the
peripheral nervous system, which includes
all the nerves that lead away from the brain
and spinal cord and the smaller nerves that
branch out from those nerves.
– Nerve conduction studies are often used to
help diagnose nerve disorders, such as
carpal tunnel syndrome.
– Identify the location of abnormal sensations,
such as numbness, tingling, or pain