3. • Differ from organ to organ
• General division into –
• Multi unit smooth muscle and
• Unitary smooth muscle
4. Figure 9.26
Small
intestine
(a) (b) Cross section of the
intestine showing the
smooth muscle layers
(one circular and the
other longitudinal)
running at right
angles to each other.
Mucosa
Longitudinal layer
of smooth muscle
(shows smooth
muscle fibers in
cross section)
Circular layer of
smooth muscle
(shows longitudinal
views of smooth
muscle fibers)
6. Peristalsis
• Alternating contractions and relaxations of smooth muscle layers that
mix and squeeze substances through the lumen of hollow organs
• Longitudinal layer contracts; organ dilates and shortens
• Circular layer contracts; organ constricts and elongates
7. Smooth Muscle
• Found in walls of most hollow organs
(except heart)
• Usually in two layers (longitudinal and circular)
8. Multi unit smooth muscle
• Composed of discrete separate smooth muscle fibers
• Each fiber operates independently of the others
• Often innervated by single nerve
• Outer surface covered by a thin layer basement membrane which
helps insulate the separate fibers from one another
• Each fiber can contract independently of the others
• Control by nerves
• Eg: eye iris, pilo-erector muscles that cause erection of hair on
sympathetic stimulation
9. Unitary Smooth Muscle
• Mass of hundred to thousands of smooth muscle fibers that contract
together as a unit
• Usually arranged in bundles or sheets
• Their cell membranes adhere to one another at multiple points so
that force generated in one fiber can be transmitted to the next
• Also, cell membranes joined by gap junctions through which ions can
flow freely from one muscle cell to the next so that AP’s or simple ion
flow without AP can travel from one to the next and cause muscle
fibers to contract together
10. Unitary Smooth Muscle
•Also known as syncytial smooth muscle
•Also known as visceral smooth muscle because it is
found in the walls of most viscera of the body
including the gut, ureter, bile ducts, uterus among
others
11. Microscopic Structure
•Spindle-shaped fibers: thin and short compared with
skeletal muscle fibers
•Connective tissue: endomysium only
•SR: less developed than in skeletal muscle
•Pouchlike infoldings (caveolae) of sarcolemma
sequester Ca2+
•No sarcomeres, myofibrils, or T tubules
15. Mechanism of contraction
• Contain both actin and myosin
• No troponin
• Lots of actin filament attached to dense bodies some of which are
attached to cell membrane and others dispersed inside the cell
• Some membrane dense cell of adjacent cells are bonded together by
protein bridges
• It is mainly through this bonds that the force of contraction is
transmitted from one cell to the next
16.
17. • Interspersed between the actin filaments are myosin filaments
• Actin filaments 5-10 times more than myosin
• Large no. of actin filaments radiate from two dense bodies.
• The ends of this filaments overlap a myosin filament located halfway
between two dense bodies
• Contractile unit same as skeletal muscle except no regularity of
skeletal muscle
• Dense bodies serve same role as Z Disc in skeletal muscle
18. Physical basis for contraction
• Doesn’t have same striated arrangement of
actin & myosin filaments in skeletal muscle
• Dense bodies serve as Z discs in skeletal m.m
• Most myosin filaments have (sidepolar) cross-
bridges → allow myosin to pull actin in one
direction in one side while simultaneously
pulling another actin in the opposite direction
on the other side → allow smooth muscle to
contract as much as 80% of its length rather
than 30% in case of skeletal muscle
19. • Also, myosin filaments have “side polar” cross bridges such that
bridges on one side hinge in one direction and those on the other
side hinge in the opposite direction
• Allows myosin to pull an actin filament in one direction on one side
while simultaneously pulling another actin filament in the opposite
direction on the side.
• This allows smooth muscle to contract as much as 80% of its length
compared with 30% for skeletal muscle
20. • Cf skeletal muscles which contract and relax rapidly, smooth muscle
has prolonged tonic long contraction which may last for hours to days
• The cycling of the myosin cross bridges (attachment to actin, then
release and so on) is much much slower cf skeletal muscle: frequency
as little as 1/10 to 1/300 rate in skeletal muscle
• Also, time for cross bridge remain attached to actin in smooth muscle
is much more cf skeletal
• reason may be that cross bridges have far less ATPase activity
• Also, only 1/10 to 1/300 of energy required to sustain same tension
as in skeletal muscle
21. • Due to slow attachment and detachment of cycling of cross
bridges
• This low energy requirement important since organs such as
intestines, urinary bladder, gall bladder and other viscera
often maintain tonic muscle contraction almost indefinitely
22. Slow onset of contraction and relaxation
• Typical smooth muscle contracts 50 – 100m/s after stimulus
• Reaches full contraction 0.5 sec later
• Declines in contractile force 1-2 sec later hence a total contraction
time of 3 seconds
• hence duration about 30times as for skeletal muscle
• Since different types of smooth muscle, duration ranges from 0.2 to
30sec
23. •Force of contraction is much higher for
smooth cf skeletal
•Due to prolonged attachment of myosin
cross bridges to actin
24. Latch mechanism
• Once smooth muscle has established connection, amount of
continuing excitation can be reduced to far less initial level with
muscle maintaining same contraction
• Energy required to maintain the contraction also very low – about
1/300 the level required for skeletal muscles
• This is called the latch mechanism
• Importance of latch mechanism is that it can maintain prolonged
tonic contraction in smooth muscle for hours with little use of energy
• Little continued excitatory signal is required from nerves or hormones
25.
26. Smooth Muscle:
• Slower in developing tension
• Sustain contractions for extended periods without fatigue
• Allows the walls of organs to maintain tension with a continued load
27.
28. Anatomy (cont.)
• Relatively little sarcoplasmic reticulum
• Lacks T-tubules
• Chemically linked to the cell membrane, rather than mechanically
linked
• Ca +2 storage is supplemented by caveolae , small vesicles that cluster
close to the cell membrane. Voltage/ligand gated Ca +2 channels
29. Response of Smooth Muscle to Stimuli
• Neurotransmitters and hormones acting on
smooth muscle can INHIBIT contraction as well as
stimulate it.
• Ca+2 influx through sarcolemma voltage gated Ca+2
channels is the signal for SR Ca+2 release
• Ca +2 storage is supplemented by caveolae , small
vesicles that cluster close to the cell membrane.
30. Stress- Relaxation of Smooth Muscle
• Ability of smooth muscle of many hollow organs to return to
nearly its original force of contraction seconds or minutes
after it has been elongated or shortened.
• After sudden increase in fluid volume in bladder, thus
stretching muscle in bladder causing an immediate increase
in pressure in bladder
• In next 15 sec or so, despite continued stretch of bladder
wall, the pressure, the pressure returns almost exactly back
to original level
31. •Then when the volume is increased another level
again, same occurs
•When volume is decreased suddenly, the pressure
falls very low at first but it then rises again to almost
near original level
•Important because it allows a hollow organ to
maintain about the same pressure inside the lumen
despite long term large changes in volume
32. Smooth muscle contraction
•Calmodulin instead of troponin
•Ca⁺⁺ combine with calmodulin
•Ca⁺⁺Calmodulin combination joins with and activates
myosin kinase, a phosporylating enzyme
•One of the light chains of the myosin heads, the
regulatory chain, becomes phosphorylated after
which it then binds with actin and the contraction
process proceeds
33. •When regulatory chain not phosphorylated, no
binding with actin
•When Ca⁺⁺ ions concentration falls below a critical
level, an enzyme, myosin phosphatase splits the
phosphate from the regulatory chain. The cycling
stops and the contraction ceases
•Time for cessation of contraction is also determined
by amount of phosphatase present
34. Figure 9.29, step 1
Calcium ions (Ca2+)
enter the cytosol from
the ECF via voltage-
dependent or voltage-
independent Ca2+
channels, or from
the scant SR.
Extracellular fluid (ECF)
Ca2+
Ca2+
Plasma membrane
Sarcoplasmic
reticulum
Cytoplasm
1
35. Figure 9.29, step 2
Ca2+
Inactive calmodulin Activated calmodulin
Ca2+ binds to and
activates calmodulin.
2
37. Figure 9.29, step 4
ATP
Pi
Pi
ADP
Inactive
myosin molecule
Activated (phosphorylated)
myosin molecule
The activated kinase enzymes
catalyze transfer of phosphate
to myosin, activating the myosin
ATPases.
4
38. Figure 9.29, step 5
Activated myosin forms cross
bridges with actin of the thin
filaments and shortening begins.
Thin
filament
Thick
filament
5
39. Nervous and hormonal controls
• Stimulated by
• Nervous
• Hormonal
• Stretch among others
• Smooth muscles has many types of receptor proteins on surface with
some stimulatory and other inhibitory
40. EXCITATION-CONTRACTION COUPLING IN
SMOOTH MUSCLE
• The mechanism differs from that of skeletal muscle.
• In skeletal muscle binding of actin and myosin is
permitted when Ca2+ binds troponin C.
• In smooth muscle, however, there is no troponin.
• Rather, the interaction of actin and myosin is controlled
by the binding of Ca2+ to another protein, calmodulin.
• In turn, Ca2+-calmodulin regulates myosin-light-chain
kinase, which regulates cross-bridge cycling.
41. • Action potentials occur in the smooth muscle cell membrane.
• The depolarization of the action potential opens voltage-gated Ca2+
channels in the sarcolemmal membrane.
• With the Ca2+ channels open, Ca2+ flows into the cell down its
electrochemical gradient.
• This influx of Ca2+ from the ECF causes an increase in intracellular
Ca2+ concentration.
42. • 2 other mechanisms may contribute to the increase in intracellular
Ca2+ conc
• :- Ligand-gated Ca2+ channels and
• :-Inositol 1,4,5-triphosphate (IP3)-gated Ca2+ release channels.
• Ligand-gated Ca2+ channels in the sarcolemmal membrane may be
opened by various hormones and neurotransmitters, permitting the
entry of additional Ca2+ from the ECF.
43. • IP3-gated Ca2+ release channels in the membrane of the sarcoplasmic
reticulum may be opened by hormones and neurotransmitters.
• Either of these mechanisms may augment the rise in intracellular
Ca2+ concentration caused by depolarization.
44. • Rise in intracellular Ca2+ causes Ca2+ to bind to calmodulin.
• Like troponin C in skeletal muscle, calmodulin binds four ions of Ca2+
• The Ca2+-calmodulin complex binds to and activates myosin-light-
chain kinase
45. • When activated, myosin-light-chain kinase phosphorylates myosin.
• When myosin is phosphorylated, it binds actin to form cross-bridges,
producing contraction.
• When myosin is in this phosphorylated state, cross-bridges can form
and break repeatedly.
• One molecule of ATP is consumed with each cross-bridge cycle.
• Amount of tension generated is directly proportional to the number
of cross-bridges formed, which is, in turn, proportional to the
intracellular Ca2+ concentration.
46. • When the intracellular Ca2+ concentration decreases, myosin is
dephosphorylated by myosin-light-chain phosphatase.
• In the dephosphorylated state, myosin can still interact with actin, but
the attachments are called latch-bridges rather than cross-bridges.
• The latch-bridges do not detach, or they detach slowly; thus, they
maintain a tonic level of tension in the smooth muscle with little
consumption of ATP.
47. • Relaxation occurs when the sarcoplasmic reticulum re-accumulates
Ca2+, via the Ca2+ ATPase, and lowers the intracellular Ca2+
concentration below the level necessary to form Ca2+-calmodulin
complexes.
48. • During the action potential in smooth muscle, Ca2+ enters the cell
from ECF via sarcolemmal voltage-gated Ca2+ channels, which are
opened by depolarization.
• Ca2+ can also enter the cell through ligand-gated channels in the
sarcolemmal membrane, or from the sarcoplasmic reticulum by IP3-
gated mechanisms
• (In contrast, in skeletal muscle the rise in intracellular Ca2+ concn is
caused exclusively by depolarization-induced release from the
sarcoplasmic reticulum-Ca2+ does not enter the cell from the ECF.)
49. •Voltage-gated Ca2+ channels are sarcolemmal
Ca2+ channels that open when the cell
membrane potential depolarizes.
•Thus, action potentials in the smooth muscle cell
membrane cause voltage-gated Ca2+ channels to
open, allowing Ca2+ to flow into the cell down
its electrochemical potential gradient.
50. • Ligand-gated Ca2+ channels also are present in the
sarcolemmal membrane.
• Not regulated by changes in membrane potential, but by
receptor-mediated events.
• Various hormones and neurotransmitters interact with
specific receptors in the sarcolemmal membrane, which are
coupled via a GTP-binding protein (G protein) to the Ca2+
channels.
• When the channel is open, Ca2+ flows into the cell down its
electrochemical gradient
52. •IP3-gated sarcoplasmic reticulum Ca2+ channels also
are opened by hormones and neurotransmitters.
•The process begins at the cell membrane, but the
source of the Ca2+ is the sarcoplasmic reticulum
rather than the ECF.
•Hormones or neurotransmitters interact with specific
receptors on the sarcolemmal membrane (e.g.,
norepinephrine with α1 receptors).
53. • These receptors are coupled, via a G protein, to
phospholipase C (PLC).
• Phospholipase C catalyzes the hydrolysis of
phosphatidylinositol 4,5-diphosphate (PIP2) to IP3 and
diacylglycerol (DAG).
• IP3 then diffuses to the sarcoplasmic reticulum, where it
opens Ca2+ release channels (similar to the mechanism of
the ryanodine receptor in skeletal muscle).
• When these Ca2+ channels are open, Ca2+ flows from its
storage site in the sarcoplasmic reticulum into the ICF
55. NMJ
• Not well developed like skeletal
• Nerves generally diffuse over a sheet of muscle fibers
• May not come into contact with muscle but form diffuse junctions
where secrete transmitter into matrix coating of smooth muscle
where it diffuses into the cells
• Where many layers of muscle, may innervate only outer layer, and
excitation travels to inner layers by AP or diffusion of transmitter
substance
56. • Transmitter mostly Ach and norepinephrine but others occur as well
• Ach excitatory transmitter in some smooth muscles and inhibitory in
others
• When Ach excites a muscle, NA inhibits it as the reverse is the case
• Because both Ach and NA bind with a receptor protein on the
membrane. Effect depends on whether the receptor protein
stimulated is excitatory or inhibitory
57. Membrane potential:
• Smooth muscle AP similar to spike of normal AP
• However, instead of rapid repolarization of muscle fiber membrane, it
is delayed for several ms to as much as one second
• This explains the prolonged contraction of smooth muscle
58. Calcium channels
• Smooth muscle has a lot of Ca⁺⁺ gated channels and very few Na
channels
• Ca⁺⁺ responsible for AP
• Occurs in same self regenerating way as for nerve fibers and skeletal
tissue
• However, the Ca⁺⁺ channels open much much slower than Na
channels and remain open much longer
• This accounts much longer for the plateau AP’s for most smooth
muscle
59.
60. • Ca ions also act directly on smooth muscle contractile mechanism to
cause contraction hence has two tasks at once
61. Slow waves in unitary muscle
• Some smooth muscle self excitatory
• AP rises from within same muscle
• Associated with a basic slow rythym
• Slow wave not an AP
• Is a local property of smooth muscle fibers that make the muscle unit
• Thought to be caused by the waning of the pumping of the +ve ions
outward through the muscle membrane
62.
63. • Also thought that the conductances to ions change rhythymically
• When peak reaches to about -35mv from the -60mv, then an AP
develops and contraction occurs
• This repetitive sequences of AP’s elicit rythmical contractions of sooth
muscle
• Slow waves called pacemaker potential
64. Types of Smooth Muscle
Single-unit (visceral) smooth muscle:
• Sheets contract rhythmically as a unit (gap junctions)
• Often exhibit spontaneous action potentials
• Arranged in opposing sheets and exhibit stress-relaxation response
65. • Ca for contraction mostly from ECF
• Time required for this diffusion is 200 -300m/s
• Called the latent period before contraction occurs
• About 50 times longer cf skeletal muscle
• When ECF Ca⁺⁺ falls to about 1/3 normal, contraction ceases
• Hence very dependent on Ca coc’n
66. • Ca ⁺⁺ removed from cell by Calcium pump
• Pump slow acting
• Hence a single contraction lasts for seconds cf hundreaths of a second
for skeletal muscle
67. Cardiac Muscles:
• Myocardial fibers
• Excitable tissue
• Have a resting membrane potential
• Between –60 to –90 mv
• Mechanism of genesis of RMP
• Similar to that in skeletal muscles
• Cardiac muscle respond
• To supra threshold stimuli by
• Generating an action potential
• Capable of propagating it
22-Feb-21 CVS Impulse generation 67
68. Myocardium
• Excitation arising in atrium or ventricles
• Spread over the unexcited tissue
• Works as a syncytium
22-Feb-21 CVS Impulse generation 68
69. Cardiac Action Potential
• General properties of cardiac AP
• Similar to that of nerve & skeletal
muscle
• Special permeability differences
• Lead to difference in shape of cardiac AP
22-Feb-21 CVS Impulse generation 69
- 85 mv
0 mv
+20 mv
0
1
4
2
3
0 = depolarization
1 = initial repolarization
2 Plateau phase
3 repolarization
70. 31-1-2017 Cardiac_Cycle.ppt 70
Depolarization in Cardiac Muscle
• Voltage-gated fast Na+ channels
open
• Rapid influx of Na+ and depolarization
• Release of Ca2+ from SR and
extracellular space
• Plateau phase: Depolarization
prolonged
• Opening K+ channels &
repolarization
71.
72. Cardiac Action Potential
• In the cardiac cells after the initial
spike
• Membrane remains deoplarized for
• About 0.1 sec in atria
• About 0.3 sec in ventricles
• Exhibiting a plateau
22-Feb-21 CVS Impulse generation 72
- 85 mv
0 mv
+20 mv
0
1
4
2
3
0 = depolarization
1 = initial repolarization
2 Plateau phase
3 repolarization
73. Cardiac Action Potential
• Depolarization
• Due to in Na+ conductance
• Opening of fast sodium channels
• Initial repolarization
• Due to closure of sodium
channels
22-Feb-21 CVS Impulse generation 73
- 85 mv
0 mv
+20 mv
0
1
4
2
3
0 = depolarization
1 = initial repolarization
2 Plateau phase
3 repolarization
74. Cardiac Action Potential
• The plateau phase
• Due to slow prolonged opening of
• Voltage gated Ca++ channels
• Become activated at potential of –
30 to –40 mv
• Also known as
• Slow calcium channels
22-Feb-21 CVS Impulse generation 74
- 85 mv
0 mv
+20 mv
0
1
4
2
3
0 = depolarization
1 = initial repolarization
2 Plateau phase
3 repolarization
75. Cardiac Action Potential
• Large amount of Ca++
• Flow through these
channels
• Prolong the period of
plateau phase
22-Feb-21 CVS Impulse generation 75
- 85 mv
0 mv
+20 mv
0
1
4
2
3
0 = depolarization
1 = initial repolarization
2 Plateau phase
3 repolarization
76. Cardiac Action Potential
• At the end of plateau phase
• Slow calcium channels
close
• Influx of Ca++ ceases
22-Feb-21 CVS Impulse generation 76
- 85 mv
0 mv
+20 mv
0
1
4
2
3
0 = depolarization
1 = initial repolarization
2 Plateau phase
3 repolarization
77. Cardiac Action Potential
• Permeability of cardiac muscle
to K+ increases
• Efflux of K+
• Return the membrane potential
to its resting value
22-Feb-21 CVS Impulse generation 77
- 85 mv
0 mv
+20 mv
0
1
4
2
3
0 = depolarization
1 = initial repolarization
2 Plateau phase
3 repolarization
78. Refractory Period
• During the action potential
• Cardiac muscle is refractory to re-
stimulation
• Cardiac impulse cannot re-
excite an already excited area
22-Feb-21 CVS Impulse generation 78
- 85 mv
0 mv
+20 mv
0
1
4
2
3
Absolute refractory
period 0.25 – 0.3 sec
Relative refractory
period 0.05 sec
79. Refractory Period
• Normal refractory period
• 0.25 to 0.3 seconds
• Approx equal to duration of
action potential
22-Feb-21 CVS Impulse generation 79
- 85 mv
0 mv
+20 mv
0
1
4
2
3
Absolute refractory
period 0.25 – 0.3 sec
Relative refractory
period 0.05 sec
80. Refractory Period
• Relative refractory period
• 0.05 seconds
• During this period
• Muscle is more difficult to excite
• But can be excited
22-Feb-21 CVS Impulse generation 80
- 85 mv
0 mv
+20 mv
0
1
4
2
3
Absolute refractory
period 0.25 – 0.3 sec
Relative refractory
period 0.05 sec
81. Refractory Period
• Refractory period
• Is due to inactivation of sodium
channels
• During prolonged depolarization
22-Feb-21 CVS Impulse generation 81
- 85 mv
0 mv
+20 mv
0
1
4
2
3
Absolute refractory
period 0.25 – 0.3 sec
Relative refractory
period 0.05 sec
82. Refractory Period
• Not until the membrane
• Has repolarized to –50 to –60 mv
• Does sodium channels recover
22-Feb-21 CVS Impulse generation 82
- 85 mv
0 mv
+20 mv
0
1
4
2
3
Absolute refractory
period 0.25 – 0.3 sec
Relative refractory
period 0.05 sec
83. Pacemaker Potential
• The cells in SAN
• Have trans- membrane potential
of
• -55 to –60 mv between discharges
• SAN cells membrane
• Naturally leaky to Na+
22-Feb-21 CVS Impulse generation 83
-60 mv
-50 mv
0 mv
+20 mv
Na+
Na+
Pacemaker
potential
84. Pacemaker Potential
• Na+ tend to leak into the cell
• Responsible for the initial phase
of pace maker potential
• Transient (T) ca++ channels open
• Entry of ca++
• Completes the pre-potential phase
22-Feb-21 CVS Impulse generation 84
-60 mv
-50 mv
0 mv
+20 mv
Na+
Na+
Ca++
Ca++ Pacemaker
potential
85. Pacemaker Potential
• The long lasting (L) ca++
channels then open
• More ca++ influx
• Which produces the impulse
22-Feb-21 CVS Impulse generation 85
-60 mv
-50 mv
0 mv
+20 mv
Na+
Na+
Ca++
Ca++ Pacemaker
potential
Ca++
86. Pacemaker Potential
• At the peak of each impulse
• K+ ion channels open
• Efflux of K+ ions
• Brings about repolarization
22-Feb-21 CVS Impulse generation 86
-60 mv
-50 mv
0 mv
+20 mv
Na+
Na+
K+
Ca++
Ca++
K+
Pacemaker
potential
Ca++
87. Pacemaker Potential
• The potassium channels then
close
• Na+ ions leak into the cell
• Causing the initial phase of pre-
potential
22-Feb-21 CVS Impulse generation 87
-60 mv
-50 mv
0 mv
+20 mv
Na+
Na+
K+
Ca++
Ca++
K+
Pacemaker
potential
Ca++
