Last edited: 8/30/2021

1. SMOOTH MUSCLE
Musculoskeletal System: Smooth Muscle Medical Editor: Dr. Sofia Suhada M. Uzir

OUTLINE

I) CHARACTERISTICS
II) TYPES OF SMOOTH MUSCLE
III) STIMULATING SMOOTH MUSCLE CELL
IV) CONTRACTION AND RELAXATION MECHANISM
V) REVIEW QUESTIONS
VI) REFERENCES

I) CHARACTERISTICS
Smooth muscle is not striated
o They do not have sarcomere
o Their myofilaments (protein filaments) are arranged
differently

Figure 2. The smooth muscle cell [Pearson Education Inc.]

(2) Movement of smooth muscle cells
Figure 1. The motor unit of smooth muscle [Lumen]
(A) MICROSCOPIC ANATOMY
(1) Structures inside the smooth muscle cell
Uninucleate
Dense bodies act as a Z-disc
→ contracts and pulls the dense bodies closer to
each other
→ shortens the thick and thin filaments
Intermediate filaments also pulls the dense bodies closer
to each other
Smooth muscle twist and squeeze itself together
→ corkscrew like action and shape

Note:
Skeletal and cardiac muscles are usually multinucleate

Plasma membrane (sarcolemma) surrounding the whole Figure 3. Muscle Contraction. The dense bodies and
cell intermediate filaments are networked through the sarcoplasm,
which cause the muscle fiber to contract. [Lumen]
Dense bodies
o Made up of alpha actinin
o Scattered throughout the smooth muscle cell
o Anchored to the plasma membrane by attachment Note:
plaques Skeletal muscle contracts → shortens by sliding
Attachment plaques myofilaments onto one another, moving the thin filaments
o Integrin proteins closer to each other
o Located at the inner cytosolic side of smooth muscle
cell
o Anchoring dense bodies to smooth muscle membrane Remember:
Sarcomere – striped structure with Z discs and 2 filaments:
Intermediate filaments
o Thick filaments which has myosin
o Composed of 2 primary proteins
o Thin filaments which have actin, tropomyosin and
 Vimentin troponin
 Desmin
o Connecting dense bodies to one another Makes up the skeletal muscle
Gives the whole muscle the ‘striped’ appearance
Thin filaments
o Made up of 2 proteins
 Actin (F)
 Tropomyosin
Thick filaments
o Composed of a primary molecule called myosin 2
o Interdigitating in between the thin filaments

SMOOTH MUSCLE MUSCULOSKELETAL: Note #1. 1 of 5

 II) TYPES OF SMOOTH MUSCLE

(A) UNITARY/SINGLE UNIT SMOOTH MUSCLE

Also called visceral smooth muscle
Interconnected with one another by gap junctions
(connexin subunits)
Innervated by autonomic nervous system
o Via the parasympathetic and sympathetic nervous
system
o Can be affected by hormones and chemical factors
o Synaptic vesicles called varicosity (Figure 1) consist
different types of neurotransmitters
 Amongst the chemicals that can be released
Figure 5. The multiunit smooth muscle with their own neurons
include and act on the smooth muscle include: and nerve endings vs single unit smooth muscle
• Norepinephrine [Online Sciences]
• Acetylcholine
• Nitric oxide Remember:
• Adenosine Skeletal muscle
o Controlled by somatic nervous system
• Substance P
Cells are electrically coupled together
o Can generate a rhythmic and simultaneous Table 1. Autonomic vs Somatic Nervous System
contraction Autonomic Nervous Somatic Nervous
o Stimulating one cell can stimulate the rest of the cells System System
Gross control Composed of Control skeletal muscle
Location parasympathetic and Voluntary action
o Entire length of gastrointestinal tract sympathetic nervous
o Urogenital tract system
Control smooth muscle
and cardiac muscle
directly
Involuntary

III) STIMULATING SMOOTH MUSCLE CELL

Smooth muscle has a stable resting membrane potential
Figure 4. The unitary smooth muscle lining the GIT and which rises upon stimulation
multiunit found in the ciliary muscle [Lumen]
(A) ON THE MEMBRANE
Interstitial cell of Cajal
Note:
Gross control utilize a lot of action creating a large and o A pacemaker cell
powerful movement o Can intrinsically depolarize depending on extrinsic
o Example: moving the entire arms innervation
o Can produce slow waves that gets really
Fine control creates a very small movement
close/exceed the threshold potential
o Example: using fingers to pick up a pen
o Creates the basic electrical rhythm
Stimulation of the cell is by causing positive ions to flow
into the cells → the inside of the cell becomes positive →
(B) MULTIUNIT SMOOTH MUSCLE reach/exceed threshold potential
Location: Inhibition of the cell is by causing positive ions to flow out
o Primarily found in iris of the cell → the cell will become negative
 Dilator and constrictor pupillae (1) Slow wave
o Ciliary muscle
 Control the lens for accommodation The rising part of the slow waves is due to the calcium
o Bronchiole smooth muscle ions (Figure 6)
o Tunica media The decreasing part is due to opening of the
 In large arteries potassium channel whenever the waves goes up
o Arrector pili without reaching the threshold
 Give you the goosebumps If the slow waves breaks the threshold point
o Spike potentials (action potentials) will be produced
Each cell has their own stimulatory/inhibitory neuron with
nerve ending (Figure 5) Slow waves can pass the threshold potential a little bit
o Not electrically coupled together without actually creating spike potentials due to
o Structurally independent to one another o Hormones/chemicals/stretch
o Will not create a rhythmic action
Fine control
o Have a lot of nerve endings, hence very excitable

2 of 5 MUSCULOSKELETAL: Note #1. SMOOTH MUSCLE


Figure 6. The slow wave [Quizlet]
(2) Calcium channels
Leaky, constantly open enough for calcium to flow into
the cell slowly
Bringing in positive ions
Membrane potential becomes more positive
Can further increase calcium flowing in by stretching
(3) Potassium channel
Leaking potassium slowly out of the cell until equilibrium
potential is reached
Inside of the cell will become more negative
Brings the membrane potential back down to rest if it
doesn’t reach the threshold
(4) Voltage gated calcium channels (Figure 7)
Located in the caveolae
Open when threshold potential is hit
Calcium starts flowing in very fast → extremely positively
charged membrane → membrane potential increases
very high
Note:
Skeletal muscles contain T tubules, not caveolae!
Figure 7. Main components of calcium signaling of the smooth
muscle cell: (3) Ca 2+ sensitive potassium channel, (4) voltage
sensitive Ca2+ channel [Research Gate]
(5) Voltage gated potassium channel
Calcium sensitive
Leaks out potassium very fast → making the inside of
the membrane to relax → decrease the membrane
potential
(6) Chemical factors
Protons, oxygen and carbon dioxide can act on smooth
muscle by either stimulating or inhibiting contraction
depending on their levels
SMOOTH MUSCLE
(7) Neurotransmitters
From the nervous system
Organ dependent
Examples:
o Acetylcholine
 Stimulate smooth muscle cell of the stomach
• By acting on muscarinic type 3 receptor
o Norepinephrine
 Inhibit smooth muscle cell of the stomach
 By acting on adrenergic receptor
(8) Hormones
Can stimulate or inhibit the smooth muscle → causes
contraction or relaxation
Causes relaxation by inhibiting the threshold potential →
negative ions to flow into the cell or positive ions to come
out of the cell
Stimulation is by causing cations to flow into the cell
Examples:
o Cholecystokinin
o Histamine
o Gastrin
(B) SECOND MESSENGER SYSTEM
Neurotransmitters such as acetylcholine released by
the nervous system stimulate the smooth muscle by
acting on muscarinic type 3 receptor
This activate GQ protein → activate phospholipase C
enzyme → degrade 2 different chemicals:
o PIP2 (Phosphatidylinositol bisphosphate) → breaking
it into 2 different components (Figure 8)
 DAG (diacylglycerol)
• Will activate protein kinase C →
phosphorylate enzymes and proteins
 IP3 (inositol triphosphate)
• Has specialized channels on the sarcoplasmic
reticulum (calcium storage factory) with a lot
of calcium ions
Inside the sarcoplasmic reticulum, calsequestrin and
calreticulin proteins hold onto calcium ions,
concentrating the calcium
o The IP3 binds to the IP3 receptor on the sarcoplasmic
reticulum → causes calcium ions to flood out →
increases the calcium ions inside the cell
Figure 8. The second messenger system which helps in the
increase in intracellular calcium level [Semantic Scholar]
Remember:
The leaky calcium channels on the cell membrane also
increases the calcium ions in the cell by flowing in calcium
→ bringing it the membrane to threshold potential →
causing voltage gated calcium channel to open → further
increases calcium inside the cell
MUSCULOSKELETAL: Note #1. 3 of 5
(1) Summary on ↑ calcium levels inside the cell
Calcium level can be increased inside the cell through:
(i) On the membrane
o Leaky calcium channels
 Pacemaker activity
o Voltage gated calcium channel
 If the leaky calcium channel hits threshold
potential
 Threshold potential reached caused by other
substances:
• Hormones
• Chemicals
• Neurotransmitters
• Stretch
(ii) Second messenger system
o Due to hormones primarily through the IP3
mechanism
(iii) Store operated calcium channels
o Depleting levels of calcium inside the sarcoplasmic
reticulum → triggers the sarcoplasmic reticulum to
make a protein (STIM) and expresses it to the
membrane → ORAI Tetramers (store operated
calcium channels) bind to STIM → ORAI tetramers
aggregate → opens extracellular fluid into the
intracellular fluid → calcium rushes into the cell
 Specialized channels on the sarcoplasm brings
the sodium out and brings the calcium into the
sarcoplasm
 There are also proton channels which can bring
protons out and calcium in but this requires the
ATP
o These increase the calcium levels in the sarcoplasmic
reticulum which later on helps in increasing the
calcium level inside the cell
IV) CONTRACTION AND RELAXATION MECHANISM
(A) CONTRACTION
When calcium levels inside the cell increase it binds to
calmodulin and form calcium calmodulin complex →
calponin, caldesmon and tropomyosin in the thin filament
will move out of the way and the following steps will
occur:
(1) Phosphorylation
Phosphorylation of regulatory light chain on the myosin →
activation of ATPase enzyme
(2) ATP hydrolysis
The detached ATP which is normally bound to myosin
cleaves into ADP and inorganic phosphate by the
ATPase enzyme
(3) Release the phosphate
The release of phosphate generates the power stroke
What is left is the inorganic phosphate and ADP
(4) Release ADP
Release of ADP and binding of another ATP
These steps are repeated which in the end:
o Causes myofilaments slide over one another
o Contraction occurs
4 of 5 MUSCULOSKELETAL: Note #1.
Remember:
(i) Importance of calcium calmodulin complex
o Inhibits calponin and caldesmin
 ATPase activity will not be inhibited
 Myosin and actin interaction wouldn’t be hindered
o Activates myosin light chain kinase enzyme
 Adds phosphate to the regulatory light chain on the
neck of myosin (phosphorylation) → stimulate
myosin ATPase activity → breaks down ATP into
ADP and inorganic phosphate
(ii) In the thin filament:
o Tropomyosin
o Calponin on the tropomyosin and actin
 Inhibits ATPase activity
 Hinders the interaction between myosin and actin
o Caldesmon with its foot on the myosin and near actin
 Inhibits ATPase activity
 Hinders the interaction between myosin and actin
Recap:
In the skeletal muscle
o The myosin head contains an ATPase which breaks
ATP into ADP and inorganic phosphate
Myosin
o Structure : head, neck and tail
o Normally it bounds to ATP which helps it to detach
(B) RELAXATION
Relaxation happens through
(1) Myosin light chain phosphatase
Removes the phosphate → myosin-ATPase activity will
be inhibited
(2) Calcium leaves the calmodulin
Calcium leaves the calmodulin and returns to the
sarcoplasmic reticulum via the calcium sodium exchange
→ the calcium calmodulin complex decreases
o calponin and caldesmon stimulated → inhibit the
ATPase activity and tropomyosin will hinder the
interaction between myosin and actin
o myosin light chain kinase enzyme will be inhibited
(3) Channels on the cell membrane (Figure 9)
There are channels that brings calcium out of the cell and
proton into the cell
There are also channels that brings calcium out of the cell
and sodium into the cell
Voltage sensitive potassium channels open → potassium
leak out of the cell with positive ions → the cell becomes
negative → the cell relaxes
Figure 9. Ion channels and transporters in smooth muscle
[Research Gate]
SMOOTH MUSCLE
 V) REVIEW QUESTIONS
Smooth muscle cells are initiated to contract by all
of the following ways except which?
a. Depolarization from a neighboring cell spread
through connexon channels
b. Norepinephrine binding to α1-adrenergic receptors
c. Acetylcholine binding to nicotinic acetylcholine
receptors
d. The movement of a bolus of food through the small
intestine
Which of the following muscle proteins plays a
critical role in contraction of both smooth and
striated muscle?
a. Calmodulin
b. Troponin
c. Tropomyosin
d. Actin
During the process of excitation-contraction
coupling in smooth muscle, intracellular [Ca2+] is
increased through all of the following methods
except which?
a. Ca2+ influx from extracellular stores through voltage-
activated Ca2+ channels
b. Ca2+ influx from the sarcoplasmic reticulum through
IP3 receptors
c. Ca2+ influx from extracellular stores through
ryanodine receptors
d. Ca2+ influx from extracellular stores through ligand-
gated Ca2+ channels
When comparing the contractile responses in
smooth and skeletal muscle, which of the following
is most different?
a. The source of activator calcium
b. The role of calcium in initiating contraction
c. The mechanism of force generation
d. The source of energy used during contraction
In excitation-contraction of smooth muscle, calcium
binds to what protein after influx into the
cytoplasm?
a. Calmodulin
b. Myosin light chains
c. Troponin
d. Tropomyosin
Which of the following enzymes is responsible for
dephosphorylating myosin light chains, thereby
causing smooth muscle relaxation?
a. Calmodulin
b. Protein kinase A
c. Myosin light chain kinase
d. Myosin light chain phosphatase
Single-unit smooth muscle differs from multiunit
smooth muscles how?
a. Single-unit muscle contraction speed is slow, while
multiunit is fast
b. Single-unit muscle has T-tubules, while multiunit
does not
c. Single-unit muscles are not innervated by autonomic
nerves
d. Single-unit muscle produces action potentials
spontaneously that spreads to neighboring cells,
while multiunit does not
SMOOTH MUSCLE
Which of the following enzymes is responsible for
phosphorylating myosin light chains in order to
activate smooth muscle contraction?
a. Calmodulin
b. Protein kinase A
c. Myosin light chain kinase
d. Phospholipase C
Which characteristic or component is shared by
skeletal muscle and smooth muscle?
a. Thick and thin filaments arranged in sarcomeres
b. Elevation of intracellular [Ca2+] for excitation-
contraction coupling
c. Spontaneous depolarization of the membrane
potential
d. High degree of electrical coupling between cells
The role of myosin light-chain protein in smooth
muscle is what?
a. Bind to calcium ions to initiate excitation-contraction
coupling
b. Phosphorylate cross-bridges, thus driving them to
bind with the thin filament
c. Split ATP to provide the energy for the power stroke
of the cross-bridge cycle
d. Dephosphorylate myosin light-chains of the cross-
bridge, thus relaxing the muscle
CHECK YOUR ANSWERS
VI) REFERENCES
● Lumen Anatomy and Physiology. Smooth muscle. Motor unit,
muscle contraction and unitary smooth muscle lining [digital images]
https://courses.lumenlearning.com/cuny-csi-ap-1/chapter/smooth-
muscle/
● Pearson Education Inc. The smooth muscle cell [digital image]
https://www.pinterest.com/pin/777926535613875418/
● Heba Soffar. Online Sciences. The multiunit smooth muscle cell
[digital image] 2021. https://www.online-
sciences.com/medecine/smooth-muscles-types-properties-function-
source-of-calcium-ions-in-smooth-muscle/
● Mohamed Trebak. Research Gate. Ion channels and
transporters [digital image] 2009.
https://www.researchgate.net/figure/Ion-channels-and-transporters-
in-vascular-smooth-muscle-The-contractile-vascular-
smooth_fig1_26779126
● Dmitry Postnov. Main components of calcium signaling [digital
image] 2011. https://www.researchgate.net/figure/Main-
components-of-calcium-signaling-of-the-vascular-smooth-muscle-
cell-1-sarcoplasmic_fig1_50349297
● Df Hayabuchi, Y.. “The Action of Smooth Muscle Cell Potassium
Channels in the Pathology of Pulmonary Arterial Hypertension.”
Pediatric Cardiology 38 (2016): 1-14. The second messenger
system [digital image] https://www.semanticscholar.org/paper/The-
Action-of-Smooth-Muscle-Cell-Potassium-Channels-
Hayabuchi/9874cdca8cdf822eae4e833c11d2d4dc798da0fb
● The slow wave graph. [digital image]
https://quizlet.com/339638287/lec-10-digestion-flash-cards/
● Sabatine MS. Pocket Medicine: the Massachusetts General
Hospital Handbook of Internal Medicine. Philadelphia: Wolters
Kluwer; 2020.
● Le T. First Aid for the USMLE Step 1 2020. 30th anniversary
edition: McGraw Hill; 2020.
● Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL,
Loscalzo J. Harrison's Principles of Internal Medicine, Twentieth
Edition (Vol.1 & Vol.2). McGraw-Hill Education / Medical; 2018
● Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ:
Pearson; 2020.
● Boron WF, Boulpaep EL. Medical Physiology.; 2017.
Guyton and Hall Textbook of Medical Physiology. Philadelphia, PA:
Elsevier; 2021. "
MUSCULOSKELETAL: Note #1. 5 of 5