Lecture 10: Smooth Muscle Physiology

Question 1

What are the two major types of smooth muscle?

Answer 1

1. Multi-unit smooth muscle
2. Unitary smooth muscle

Question 2

What are the differences between multi-unit smooth muscle and unitary SM.

Answer 2

In MUSM, 1 muscle cells is innervated by 1 nerve. This allows for finer control.

Examples are ciliary muscle of the eye, iris and piloerector muscle.

Unitary smooth muscles has cells that are connected together and even though there are multiple cells there, they act as a single unit. The reason they can do this is because there is a lot of interconnected units between neighboring cells via gap junctions (junctions that allow rapid transmission of signals).

Examples are GI tract, bile ducts and uterus.

Question 3

In terms of contraction, how is smooth muscle different from skeletal muscle and cardiac muscle?

Answer 3

-Smooth muscle does not have sarcomeres, but has more actin than skeletal m.

-Skeletal muscle has more myosin.

• Actin is attached to dense bodies/adheren junctions
• Myosin heads are arranged bi-directionally.

Question 4

In terms of the cross-bridge cycle, how is smooth muscle different than skeletal muscle?

Answer 4

In smooth muscle, the myosin cross bridge cycle is slower and the time that myosin and actin are attached is greater, creating a creater force. Because of this, the demand for ATP is lower.

Question 5

As we have discussed, in smooth muscle as excitation slows, contraction remains. What is this called?

Answer 5

Latch mechanism

Question 6

Describe the process of excitation-contraction coupling in smooth muscle.

Answer 6

1. Ca2+ influx into the cytoplasm from the ECF via [L-type VGCa2+ channels and ligand gated Ca2+ channels]
2. A small amount of Ca2+ is released from the SR via the [IP3 gated Ca2+ released channels and ryanodine receptors]
3. Combines with calmodulin –> Ca2+-calmodulin complex
4. • the myosin light chain kinase (MLCK)
5. Phosphorylation of myosine light chains
6. • myosine ATP-ase
7. Allows the binding of actin and myosin–> tension
8. Relaxation occurs when Ca2+ pumps remove Ca+ and MLCPhosphotase removes the phosphate group on the MLC.

Question 7

What characteristic or component is shared by skeletal muscle and smooth muscle?

Answer 7

Increase of intracellular [Ca2+] for excitation-contraction coupling.

Question 8

Smooth muscle does not sarcomeres, T-tubules, troponin or tropomyosin.

Thus, how do we transmit electrical signals to the depths of smooth muscle?

Answer 8

Smooth muscle have caveolae, underdeveloped t-tubules like system.

Question 9

How does Ca2+ exit smooth muscle?

Answer 9

1. SERCA
2. 3Na+/Ca2+ antiporter
3. Sarcolemma Ca2+ ATPase.

Question 10

Contraction of smooth muscle is usually proportional to what?

Answer 10

Ca2+ levels.

Question 11

What are the four major ways smooth muscle can be stimulated to contract?

Answer 11

1. Nerves

2. Hormones

3. Stretch

4. Environment

—-This is very different than how skeletal muscle can be contracted—-

Question 12

How can nerves stimulate smooth muscle?

Answer 12

Nerves have variscosities (diffuse junctions), which can release NT such as ACh, NE and EPI.

The distance between the variscosities and the fibers differ.

Question 13

NE and EPI can be inhibitory or excitatory depending on the receptor they bind to. What happens when they bind to beta-2 receptors and alpha-1 receptors?

Answer 13

Alpha-1 receptors–> Constriction

Beta-2 receptors–> Dilation

Question 14

What do

Angiotensin II,

Vasopressin,

Endothelin do?

Answer 14

cause CONTRACTION

Question 15

What do adenosine and NO do?

Answer 15

They cause relaxation- vasodilation

Question 16

What are the 4 main hormones that control smooth muscle?

Answer 16

1. CCK (contracts the gallbladder)

2. 5HT

3. Histamine

4. Oxytocin

When they bind to their receptor, they affect Ca2+ channels.

Question 17

What are the 4 main environmental cues that control smooth muscle?

Answer 17

1. Hypoxia
2. Too much CO2
3. Increased H+
4. Adenosine, LA, increased K+

ALL CAUSE VASODILATION

Question 18

What are the two main pathways that increase intracellular Ca2+?

Answer 18

1. VDCC (Voltage-dependent Ca2+ channels)
2. Ligand-gated Ca2+ channels (GCPRs), which causes activate pathways that open VGNa2+ channels and cause PLC–> PIP2–> IP3 and DAG. IP3 will then bind to IP3-R and cause the relese of Ca2+ from the SR.

Question 19

The latch mechanism allows for binding with what kind of myosin ATPase?

Answer 19

Slow to fatigue slow myosin.

Question 20

What is the RMP of smooth muscle?

Answer 20

-50 to -60 mV

Question 21

What types of AP can occur in unitary SM?

Answer 21

1. AP with plateus
2. AP with spiked potentials

Question 22

How are the AP in skeletal m different from the AP in smooth muscle?

Answer 22

• In skeletal muscle, contraction occurs via the 1 AP, then contraction stops.
• In smooth muscle, we VGCCa+ (L-type) can cause oscilations with spiked AP. This will then cause K+ efflux via (Ca2+-activated K+ channels).
• This is stimulated by hormones, NTs, stretch or can be spontaneous.

Question 23

How are plateus in smooth m. initiated?

Answer 23

NT

and

stretch

Question 24

In skeletal muscle, action potentials are initated by an influx of Na+.

What causes AP to occur in smooth muscle? Why?

Answer 24

Ca2+.

This occurs because smooth muscle has less VGNa+ channels and more VGCa2+ channels that open slower and stay open longer.

Question 25

Describe the latch mechanism seen in smooth muscle.

Answer 25

Actin and myosin are still latched even after phosphate is removed because it has low affinity for ATP and ATP is needed to un-latch

These latched myosin-actin will generate active tension without the use of ATP —causing smooth muscle to remain contracted (20-30%).

Question 26

Smooth muscle is able to continuously rearrange itself to reduce passive tension so it is able to stretch more.

What is the difference in active tension between skeletal and smooth muscle?

Answer 26

Skeletal muscle has one optimal area where tension and length are best.

Smooth muscle due to actin rearrangment and aligning allows more stretch while also keeping tension relatively higher, where as in skeletal muscle we would see a drop once we pass a certain stretch length.

Question 27

How does the SR between skeletal m and smooth muscle differ?

Answer 27

Skeletal m. has a large, well-defined SR with triads and well developed T-tubules

Smooth muscle has a poorly developed SR, no tubules. Instead, it has caveoli.

Question 28

What are the thin filaments in skeletal m and smooth?

Answer 28

Skeletal muscle–> actin, tropomyosin, troponin

Smooth muscle–> actin and tropomyosin

Question 29

What has more thin filaments: skeletal m or smooth muscle?

Answer 29

Smooth muscle.

Question 30

What is the thick filament composition of smooth muscle and skeletal muscle?

Answer 30

Skeletal muscle–> myosin with a fast ATPase.

Smooth muscle–> Myosin with a slow ATPase.

Question 31

NT in skeletal muscle and smooth muscle.

Answer 31

Skeletal muscle–> ACh (excitatory) binds to nAChR

Smooth muscle–> ACh, EPI, NE can be excitatory or inhibitory depending on the receptor they bind to: muscarinic or adrenergic

Question 32

Does smooth muscle need an AP?

Answer 32

Skeletal muscle needs to be activated by a AP

SM can be be activated by pacemajer potential, IP3 and hormones

Question 33

What is the mechanism that allows myosin and actin to interact in skeletal m and smooth m

Answer 33

Skeletal m–> tropomyosin is moved by troponin

Smooth m–> myosin light chains are phosphorylated

Question 34

What causes relaxation in skeletal m and smooth muscle

Answer 34

Skeletal muscle–> removal of Ca2+ from troponin

Smooth muscle–> activation of light chain phosphotase

Question 35

How is excitation of smooth muscle initiated?

Answer 35

MANY WAYS