Molecular mechanism of Muscle contraction

1. Molecular Mechanism of
Muscle Contraction
Dr. Sai Sailesh Kumar G
Associate Professor
Department of Physiology
NRIIMS
Email: dr.goothy@gmail.com

2. Explain
A dead body in a state of extreme rigidity and stiffness is found by
the police.
What is this condition called?
Give its physiological basis?
Comment on whether death had occurred within 24 hours or after
that?

3. Latent Period
A single action potential in a skeletal muscle fiber lasts only 1 to 2 msec.
The onset of the resulting contractile response lags behind the action potential
because the entire excitation–contraction coupling must occur before cross-bridge
activity begins.
In fact, the action potential is over before the contractile apparatus even becomes
operational.
This time delay of a few milliseconds between stimulation and onset of contraction
is called the latent period

5. Sequence of events
Nerve Action Potential
Muscle Action Potential
Muscle Contraction

6. Contraction time
The time from contraction onset until peak tension develops
contraction time—varies from 15 to 50 msec,
depending on muscle fiber type

7. Relaxation time
The time from peak tension until relaxation is complete—
relaxation time—varies from 15 to 50 msec,
again depending on muscle fiber type.

8. Simple muscle curve
What is the difference between AP and simple muscle curve?

9. Skeletal Muscle Mechanics
The about 600 skeletal muscles in the body range in size from delicate
external eye muscles that control eye movements and contain only a
few hundred fibers to large, powerful leg muscles that contain several
hundred thousand fibers.
Each muscle is sheathed by connective tissue

10. Skeletal Muscle Mechanics
The connective tissue extends beyond the ends of the muscle to form
tough, collagenous tendons that attach the muscle to bones.
Tension is produced internally within the sarcomeres,
considered the contractile component of the muscle,
as a result of cross-bridge activity
and the resulting sliding of filaments.

11. Skeletal Muscle Mechanics
However, the sarcomeres are not attached directly to the bones.
Instead, the tension generated by these contractile elements must be
transmitted to the bone via a tendon before the bone can be moved.
Tendons have a certain degree of passive elasticity.
This noncontractile elastic tissue is in series with the contractile
component is called the series-elastic component of the muscle

12. Skeletal Muscle Mechanics
Shortening of the sarcomeres
stretches the series-elastic component (tendon).
Muscle tension is transmitted to the bone by this tightening of the
series-elastic component.
This force applied to the bone moves the bone against a load.

13. Skeletal Muscle Mechanics
A muscle is typically attached to at least two bones across a joint by
means of tendons that extend from each end of the muscle.
The end of the muscle attached to the more stationary part of the
skeleton is called the origin,
and the end attached to the skeletal part that moves is the insertion.

14. Skeletal Muscle Mechanics
muscle contraction can only pull and not push bone
biceps can pull the joint in one direction (flexion)
and the triceps can pull the joint in the other direction (extension).

16. 16

17. Simple muscle twitch
The momentary contraction of
the muscle in response to electrical stimulation
is called simple muscle twitch. The contraction
recorded on a moving kymograph is known as a
simple muscle curve.
17

18. The latent period (0.01sec):
Is the period from the point of
stimulus to the point of onset of contraction.
18

19. The contraction period(0.04sec):
Beginning from the point of
contraction to the peak of contraction.
The relaxation period(0.05sec):
Is the period from the peak of
contraction to the end of relaxation.
19

20. Latent period (AB) = 0.01 sec
Contraction period (BC) = 0.04 sec
Relaxation period (CD) = 0.05 sec
Total twitch duration in the frog’s
gastropnemius muscle = 0.1 sec
20

21. Cause of latent period
The brief interval between the
moment of stimulation and the start of
contraction is called the latent period.
The latent period is due to:
1. The time taken by the APs to travel from the
point of stimulation to the motor endplates
21

22. 2. Time taken to release acetylcholine,
sodium influx, and generation of
muscle action potential which leads to
contraction.
3. Viscosity of the muscle.
4. Inertia of the lever system
22

23. The muscle contraction recorded
in this experiment is the isotonic type.
23

24. SMT
After complete
relaxation
Late relaxation
Early relaxation Contraction period Refractory period
24

25. Effect of two successive stimuli on muscle
contraction.
The 2nd stimuli is applied
successively in different stages of contraction:
25

26. 1. Simple muscle twitch
2. 2nd stimulus given in 1st half of latent period
– no change since it falls in the absolute
refractive period of the first stimulus.
26

27. 3. 2nd stimulus falls in contraction period or
second half of latent period, causing
increase in amplitude of the curve, this is
called summation.
27

28. 4. When the 2nd stimulus falls in the early
relaxation period of the first stimulus,
relaxation is arrested and the 2nd curve
recorded is higher in magnitude then the
first
28

29. 5. When the 2nd stimulus is applied after the
relaxation is complete 2nd twitch is recorded
which is higher in magnitude than the first
one. The increase in magnitude of the
second twitch is also due to the beneficial
effect.
29

30. Causes for beneficial effect
1. Decreased viscosity as a result of 1st curve
2. Increased temperature of muscle
3. Increased calcium content
All these factors facilitate 2nd contraction hence
more force of contraction -beneficial effect.
30

31. 31

32. Effect of Temperature variation on simple
muscle twitch.
Normal – room temperature
1. Warm ringer – all phases shortened
amplitude of the curve increases
2. Cold ringer – all phases prolonged amplitude
decreased.
32

33. Effects of Hot Ringer
1. Do not raise temperature above 40o C-
coagulation of enzyme occurs
2. Increase temperature with in physiological
limits.
3. Decreased viscosity increases conduction
impulse in muscle.
33

34. Effects of Cold ringer
1. Depresses muscle activity,
2. Slows enzyme reactions,
3. General slowing effect on contraction and
relaxation.
34

35. Clonus Tetanus
Single
contraction
35
Lever touches
base line
Contraction powerful start
immediately
Treppe (stair
case effect)

36. Genesis of tetanus
State of sustained tonic
contraction of the muscle without
relaxation due to rapid repeated
stimulation.
36

37. Set up a nerve – muscle
preparation and stimulate it with gradually
increasing frequencies.
37

38. a. 5 stimuli per second:
Each contraction starts after
complete relaxation of the previous twitch,
with brief intervals between them.
Contraction show a progressive
increase in force. This phenomenon is
called the ‘staircase effect’
38

39. b. 10 stimuli per second:
Successive contractions
begin immediately after the lever
touches the base line. The contractions
are also more forceful due to beneficial
effect.
39

40. c. 15-25 stimuli per second:
Since the interval
between the stimuli is less than 0.1 sec,
successive contractions begin before the
relaxations are completed.
40

41. The graph shows a progressive
increase in amplitude up to a certain level
beyond which there is no further increase a
phenomenon called ‘treppe’ or staircase
effect is seen.
41

42. 42
Clonus: if the muscle is stimulated below the
tetanizing frequency incomplete tetanus occurs.

43. d. More than 30-40 stimuli per second:
With such high rates,
successive stimuli arrive before the muscle
begins to relax, so that it remains in a state
of sustained, smooth, and forceful
contraction called tetanus.
43

44. 44

45. 45

46. 46

47. Effect of load on Muscle contraction
After – load
Load acts on the muscle only when
muscle begins to contract i.e. muscle is not
stretched, initial length of the muscle is not
altered.
47

48. Free load
Load acts on the muscle both at rest and
during contraction initial length of the muscle
is increased.
Force of contraction is greater in free
load when compared to after load. At any
given weight greater degree of contraction
occurs in free – load than after load.
48

49. 49
Starling’s Law
Upto a limit, greater the initial length,
greater is the force of contraction.
There is an optimal length, at which
the force generated by the muscle is
maximal.

50. 50

51. 51
Fatigue
When a muscle is stimulated repeatedly
for a prolonged period of time, it loses its
physiological property of contraction – a
phenomenon called fatigue develops.
It regains its properties after some rest,
hence it is a reversible phenomenon.

52. 52
The first few contractions increase in
amplitude due to beneficial effect. As
stimulation is continued, there is a
progressive increase in latent period, and a
decrease in amplitude. The rise of tension is
slower, and relaxation is more gradual and
incomplete.

53. 53
Finally, the muscle fails to contract
altogether and the lever does not return to the
base line.

54. 54
The cause of fatigue
1. Depletion of acetylcholine from the motor
nerve endings
2. Interference with neuromuscular
transmission by substances like pyruvic and
lactic acids, and breakdown products of ATP

55. 55
3. Too rapid contractions cause too little time
available for resynthesis of Ach.
4. Fall of pH
5. exhaustion of glycogen
6. Exhaustion of ATP (ATP molecules are
required for detachment of myosin heads
from actin)

56. 56
Causes of Beneficial Effects of First Few
Contractions
1. Increase in temperature
2. Increase in enzymatic activity
3. Reduction in viscosity in intracellular matter.
4. Increased calcium concentration within the
muscle fiber.

57. 57
Seat of Fatigue
1. In an isolated muscle:
(a) After the muscle undergoes fatigue
it responds briskly to direct stimulation of
its nerve.

58. 58
(b) Direct stimulation of muscle also causes
contraction
This clearly shows that seat of
fatigue is neuromuscular junction.

59. 59
Seat of fatigue in an intact body
CNS is the main seat of fatigue.
The muscles develop fatigue latter

60. 60
Delay in relaxation period is an
early sign of fatigue. When fatigue sets in,
the muscles is unable to relax fully and
remains in a state of partial contraction
called contraction remainder.

61. THANK YOU