Physiology of Smooth Muscle

1. Contractile Mechanism of Smooth muscle
Prof. Dr. Rashid Mahmood

2. 2
Surah: 33 Al Ahzab Aya: 21
06:35 AM
Prof. Dr. Rashid Mahmood
Contractile Mechanism of
Smooth muscle

3. Objectives (SEQs)
 Goal /Aim
By the end of this session students should be able to
understand the Basic Concepts regarding Functional
characteristics of Smooth Muscle
 Specific objectives:
At the end of the lecture students should be able to
Explain the Molecular and Chemical basis of contraction smooth
muscle cells .
Describe Latch Phenomenon.
Identify mechanisms regulating the smooth muscle contraction.
Describe the mechanism of smooth muscle Contraction and Relaxation.
Describe the effect of Local Tissue Factors and Hormones to cause
Smooth Muscle Contraction
Compare the Contraction of Smooth and Skeletal Muscle
Describe the physiological anatomy of smooth muscle neuromuscular
junction.
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4. 4
Contractile Mechanism
in Smooth Muscle
06:35 AM Prof. Dr. Rashid Mahmood

5. Innervation of smooth muscle
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6. Gap junctions

7. 7
Physical Basis for Smooth
Muscle Contraction
06:35 AM Prof. Dr. Rashid Mahmood

8. 8
Physical Basis for Smooth
Muscle Contraction
• No striated arrangement of actin and myosin filaments
• actin filaments attached to so-called dense bodies
– Some attached to the cell membrane
– Others dispersed inside the cell.
– Some of the membrane dense bodies of adjacent cells bonded together by
intercellular protein bridges.
• the force of contraction is transmitted from one cell to the next through
these bonds
• myosin filaments: Interspersed among the actin filaments
– diameter : more than twice that of the actin filaments.
– Number: 5 to 10 times as many actin filaments as myosin filaments
• Arrangement:
– actin filaments radiating from two dense bodies; the ends of these filaments
overlap a myosin filament located midway between the dense bodies.
• This contractile unit is similar to the contractile unit of skeletal muscle, but without the
regularity of the skeletal muscle structure
– (dense bodies of smooth muscle serve the same role as the Z discs in skeletal
muscle)
• smooth muscle cells can contract as much as 80 per cent of their length ( less
than 30 per cent in skeletal muscle)
06:35 AM Prof. Dr. Rashid Mahmood

9. 9
Chemical Basis for Smooth
Muscle Contraction
• actin and myosin filaments
• chemical characteristics similar to those of the actin and myosin
filaments in skeletal muscle
• no troponin complex
• actin and myosin filaments interact with each other in much the
same way
• contractile process is activated by calcium ions, and ATP is
degraded to ADP to provide the energy for contraction.
• major differences
– physical organization
– excitation-contraction coupling
– control of the contractile process by calcium ions
– duration of contraction
– amount of energy required for contraction.
06:35 AM Prof. Dr. Rashid Mahmood

10. Assessment Q.1
1.There are ________ times as many
actin filaments as myosin filaments in
smooth
A.1
B.2
C.5 to 10
D.6
E.10 to 20
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Energetics of muscle
contraction | © Prof. Dr.
Rashid Mahmood
Jan 6, 2018
C

11. Arrangement of myofilaments in smooth muscle
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12. Comparison of role
of Ca++ in skeletal
and smooth muscle
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13. Mechanism of
skeletal
muscle
contraction
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14. 06:35 AM Prof. Dr. Rashid Mahmood 14

15. 06:35 AM Prof. Dr. Rashid Mahmood 15
Mechanism of
skeletal
muscle
Relaxation

16. Assessment Q.2
1.Which one of the flowing is not present
in smooth muscle
A.Myosin kinase
B.Myosin phosphatase
C.Calmodulin
D.Troponin
E.Tropomyosin
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Energet
ics ofJan 6, 2018
C

17. 17
Comparison of Smooth Muscle Contraction and
Skeletal Muscle Contraction
• most smooth muscle contraction is prolonged
tonic contraction, sometimes lasting hours or
even days
– most skeletal muscles contract and relax rapidly
• physical and the chemical characteristics of
smooth muscle versus skeletal muscle contraction
are different
• Differences:
06:35 AM Prof. Dr. Rashid Mahmood

18. 18
Differences between Smooth
Muscle Contraction and Skeletal
Muscle Contraction
1. Slow Cycling of the Myosin Cross-Bridges
2. Energy Required to Sustain Smooth Muscle
Contraction
3. Slowness of Onset of Contraction and
Relaxation
4. Force of Muscle Contraction
5. "Latch" Mechanism for Prolonged Holding
of Contractions of Smooth Muscle
6. Stress-Relaxation of Smooth Muscle
06:35 AM Prof. Dr. Rashid Mahmood

19. 19
1. Slow Cycling of the Myosin
Cross-Bridges
• (attachment to actin, then release from the actin,
and reattachment for the next cycle)
– frequency = 1/10 to 1/300 that in skeletal muscle
– fraction of time that the cross-bridges remain
attached to the actin filaments (a major factor that
determines the force of contraction):
• greatly increased in smooth muscle
– reason :
• cross-bridge heads have far less ATPase activity than
in skeletal muscle, so that degradation of the ATP that
energizes the movements of the cross-bridge heads is
greatly reduced, with corresponding slowing of the rate of
cycling.
06:35 AM Prof. Dr. Rashid Mahmood

20. 20
2. Energy Required to Sustain
Smooth Muscle Contraction
• Only 1/10 to 1/300 as much energy is required to
sustain the same tension of contraction in smooth
muscle as in skeletal muscle
• Mechanism:
– slow attachment and detachment cycling of the
cross-bridges
• because only one molecule of ATP is required for
each cycle, regardless of its duration.
– This sparsity of energy utilization by smooth muscle
is exceedingly important to the overall energy
economy of the body ( tonic muscle contraction)
06:35 AM Prof. Dr. Rashid Mahmood

21. 21
3. Slowness of Onset of
Contraction and Relaxation of
Smooth Muscle Tissue
• total contraction time of 1 to 3 seconds (Range: 0.2
second to 30 seconds)
• (30 times as long as a single contraction of an average skeletal
muscle fiber)
– Onset of contraction: 50 to 100 milliseconds after it is
excited
– Achievement of full contraction: about 0.5 second later
– decline in contractile force: in another 1 to 2 seconds
• Mechanism:
1. slowness of attachment and detachment of the cross-
bridges with the actin filaments
2. slower response to calcium ions
06:35 AM Prof. Dr. Rashid Mahmood

22. Video of Calmodulin
2206:35 AM Prof. Dr. Rashid Mahmood

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24. Assessment Q.3
• Why the Myosin Cross-Bridges Cycling in smooth
muscles is slower than skeletal muscle?
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ics ofJan 6, 2018

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4. Force of Muscle Contraction
• greater than that of skeletal muscle
– 4 to 6 kg/cm2 cross-sectional area for smooth
muscle
– (3 to 4 kilograms for skeletal muscle)
• Despite
– few myosin filaments
– slow cycling time of the cross-bridges
• Mechanism:
– prolonged period of attachment of the myosin
cross-bridges to the actin filaments.
06:35 AM Prof. Dr. Rashid Mahmood

26. 26
5. "Latch" Mechanism for
Prolonged Holding of
Contractions of Smooth Muscle
• Definition: muscle maintains its full force of
contraction despite reduced amount of
continuing excitation and lesser energy required
for comparable sustained skeletal muscle
contraction
• importance :
– it can maintain prolonged tonic contraction in
smooth muscle for hours with little use of energy.
• Little continued excitatory signal is required
from nerve fibers or hormonal sources.
06:35 AM Prof. Dr. Rashid Mahmood

27. 27
6. Stress-Relaxation of Smooth
Muscle
• important characteristic of smooth muscle, especially the
visceral unitary type of smooth muscle of many hollow
organs
• Definition: ability to return to nearly its original force of
contraction seconds or minutes after it has been
elongated or shortened.
• Example:
– change in fluid volume in the urinary bladder
• These phenomena are called
– stress-relaxation and reverse stress-relaxation.
• importance :
– except for short periods of time, they allow a hollow organ to
maintain about the same amount of pressure inside its
lumen despite long-term, large changes in volume.
06:35 AM Prof. Dr. Rashid Mahmood

28. 28
Regulation of Contraction by
Calcium Ions
• initiating stimulus :
– an increase in intracellular calcium ions
• Mechanism of increase in intracellular calcium
ions
1. nerve stimulation
2. hormonal stimulation
3. stretch of the fiber
4. change in the chemical environment of the fiber
– smooth muscle does not contain troponin
– different mechanism
06:35 AM Prof. Dr. Rashid Mahmood

29. 29
Calmodulin, Myosin Kinase and
Phosphorylation of the Myosin Head
• In place of troponin, smooth muscle cells contain
a large amount of another regulatory protein
called calmodulin.
– similar to troponin BUT different in the manner in
which it initiates contraction.
– Calmodulin does this by activating the myosin cross-
bridges.
06:35 AM Prof. Dr. Rashid Mahmood

30. 3006:35 AM Prof. Dr. Rashid Mahmood

31. 31
Sequence of events
– The calcium ions bind with calmodulin.
– The calmodulin-calcium combination joins with and
activates myosin kinase, a phosphorylating enzyme.
– One of the light chains of each myosin head, called the
regulatory chain, becomes phosphorylated in response
to this myosin kinase.
– when the regulatory chain is phosphorylated, the head has the
capability of binding repetitively with the actin
filament and proceeding through the entire cycling process of
intermittent "pulls," the same as occurs for skeletal muscle,
thus causing muscle contraction.
06:35 AM Prof. Dr. Rashid Mahmood

32. Assessment Q.4
• Define “Latch Mechanism” in smooth muscles.
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Energet
ics ofJan 6, 2018

33. 33
Cessation of Contraction-Role
of Myosin Phosphatase
• When the calcium ion concentration falls below a critical
level, the aforementioned processes automatically
reverse, except for the phosphorylation of the myosin
head.
• Reversal of this requires another enzyme, myosin
phosphatase, located in the fluids of the smooth muscle
cell, which splits the phosphate from the regulatory light
chain. Then the cycling stops and contraction ceases.
• The time required for relaxation of muscle contraction,
therefore, is determined to a great extent by the amount
of active myosin phosphatase in the cell.
06:35 AM Prof. Dr. Rashid Mahmood

34. 34
Mechanism for Regulation of the
Latch Phenomenon
• When the myosin kinase and myosin phosphatase enzymes are
both strongly activated, the cycling frequency of the myosin heads
and the velocity of contraction are great.
• Then, as the activation of the enzymes decreases, the cycling
frequency decreases, but at the same time, the deactivation of
these enzymes allows the myosin heads to remain attached to the
actin filament for a longer and longer proportion of the cycling
period.
• Therefore, the number of heads attached to the actin filament at
any given time remains large.
• Because the number of heads attached to the actin determines the
static force of contraction, tension is maintained, or "latched"; yet
little energy is used by the muscle, because ATP is not degraded to
ADP except on the rare occasion when a head detaches.
06:35 AM Prof. Dr. Rashid Mahmood

35. 35
Nervous and Hormonal Control
of Smooth Muscle Contraction
• skeletal muscle fibers are stimulated exclusively by the
nervous system
• smooth muscle can be stimulated to contract by
multiple types of signals:
1. nervous signals
2. hormonal stimulation
3. stretch of the muscle etc
• reason :
– many types of receptor proteins that can initiate the
contractile process.
– other receptor proteins inhibit smooth muscle contraction
(another difference from skeletal muscle)
06:35 AM Prof. Dr. Rashid Mahmood

36. 36
Importance of Calcium Channels
in Generating the Smooth Muscle
Action Potential
• more voltage-gated calcium channels ( few voltage-
gated sodium channels)
• Therefore, flow of calcium ions to the interior of the
fiber is mainly responsible for the action potential.
• calcium channels open many times more slowly than do
sodium channels,
• and they also remain open much longer. → prolonged
plateau
• calcium performs two tasks at once
1. action potential
2. calcium ions act directly on the smooth muscle
contractile mechanism to cause contraction.
Prof. Dr. Rashid Mahmood

37. 37
Excitation of Visceral Smooth
Muscle by Muscle Stretch
• Mechanism:
(1) the normal slow wave potentials
(2) decrease in overall negativity of the membrane
potential caused by the stretch itself.
• Importance:
– when excessively stretched→ contract
automatically and rhythmically.
• Example:
– intestine
Prof. Dr. Rashid Mahmood

38. 38
Factors that Cause Smooth Muscle
Contraction Without Action Potentials
(1) local tissue chemical factors and
(2) various hormones.
Prof. Dr. Rashid Mahmood

39. 39
Smooth Muscle Contraction in Response to
Local Tissue Chemical Factors
1. oxygen
2. carbon dioxide
3. hydrogen ion concentration
4. Adenosine
5. Lactic acid
6. potassium ions
7. calcium ion concentration and
8. body temperature
Prof. Dr. Rashid Mahmood

40. 40
Effects of Hormones on Smooth
Muscle Contraction
1. norepinephrine,
2. Epinephrine,
3. acetylcholine,
4. angiotensin,
5. endothelin,
6. Vasopressin,
7. Oxytocin,
8. serotonin, and
9. histamine.
• Receptors:
– hormone-gated excitatory receptors
– hormone-gated inhibitory receptors
Prof. Dr. Rashid Mahmood

41. 41
Mechanisms of Action of Hormones
or Local Tissue Factors.
• Changes in ion permeabilities (Na+, K+, Ca++)
– Inhibit/ Excite
• Changes in intracellular enzyme activity
– Inhibit/ Excite
– Second messenger system of receptors
Prof. Dr. Rashid Mahmood

42. 42
Source of Calcium Ions That
Cause Contraction
(1) Through the Cell Membrane
(2) from the Sarcoplasmic Reticulum
• sarcoplasmic reticulum is less developed in most
smooth muscle
• almost all the calcium ions that cause contraction
enter the muscle cell from the extracellular fluid
at the time of the action potential or other
stimulus.
• latent period : time required for this diffusion of
Ca++ (200 to 300 milliseconds , about 50 times
as great as for skeletal muscle contraction.
Prof. Dr. Rashid Mahmood

43. 43
Smooth Muscle Sarcoplasmic
Reticulum
Rudimentary
T-Tubules
Prof. Dr. Rashid Mahmood

44. 44
Role of the Smooth Muscle
Sarcoplasmic Reticulum.
• release of calcium ions from the skeletal muscle
longitudinal sarcoplasmic tubules
• The more extensive the sarcoplasmic reticulum in
the smooth muscle fiber, the more rapidly it
contracts.
• the force of contraction of smooth muscle usually
is highly dependent on extracellular fluid calcium
ion concentration ( as sarcoplasmic reticulum is
less developed in most smooth muscle)
Prof. Dr. Rashid Mahmood

45. 45
A Calcium Pump Is Required to
Cause Smooth Muscle Relaxation
• to pump calcium ions out of the smooth muscle
fiber back into
1. extra-cellular fluid, or into
2. sarcoplasmic reticulum, if it is present.
• This pump is slow-acting in comparison with
the fast-acting sarcoplasmic reticulum pump in
skeletal muscle →
• Smooth muscle contraction often lasts longer
(for seconds) rather than hundredths to tenths of
a second, as occurs for skeletal muscle.
Prof. Dr. Rashid Mahmood

46. Learning Resources
• Guyton and Hall (Text book of physiology), 13th Edition
• Ganong (Text book of physiology), 25th Edition
• Human Physiology : from cells to system Lauralee
Sherwood,9th
Edition
• Human Physiology Stuart Ira Fox, 13th Edition
• Robert M. Berne, Matthew N. Levy. Physiology, 7th
edition
• Internet
Energetics of muscle
contraction | © Prof. Dr.
Rashid Mahmood
46
Jan 6, 2018

47. Comparison
of contractile
process in
different
muscle types
Jan 6, 2018 Energetics of muscle contraction | © Prof. Dr. Rashid Mahmood 47
Human
Physiology : from
cells to system
Lauralee
Sherwood,9th
Edition (Table 8-4)

48. ThankYou
Jan 6, 2018 Energetics of muscle contraction | © Prof. Dr. Rashid Mahmood 48
ANY QUESTIONS?
drrashid62@gmail.com
rashid.mahmood@rmi.edu.pk