Smooth Muscle 

Study Guide
Gwen V. Childs, Ph.D.
Room Shorey 9/34
Re
ad pp 178-182, Gartner and Hiatt 

Test yourself:  How much do you know about smooth muscle?

1)      What are  major histological features you would use to distinguish smooth muscle from striated muscle types?

2)      Name one similarity you would find when comparing smooth and cardiac muscle.

3)      How would you distinguish smooth muscle from connective tissue?

4)      Where would you find smooth muscle?

5)      Describe the ultrastructure of smooth muscle cells including the function of each major region or domain. In particular, be able to describe and identify:

a.      Caveolae

b.      Focal densities

c.      Sources of energy

d.      Gap junctions

e.      Bundles of thick and thin filaments

6)      How are smooth muscle cells structured to sustain the long wave like contractions.

a.      Describe the process of contraction

b.      What structure is equivalent (in function) to the T-tubules of striated muscle?

c.      How is smooth muscle regulated?

d.      What is the difference between single unit (unitary) or multiunit muscle groups?

7)      How does the connective tissue sheath help organize smooth muscle function?

8)      Describe myoepithelial cells, or myofibroblasts and their functions. 

9)  What disease states involve smooth muscle cells?

What are the major histological features of smooth muscle?

            Smooth muscle cells are spindle shaped.  They have one centrally placed nucleus per cell and are usually organized in small clusters of cells. Fine collagenous, reticular connective tissue separates each cell and the bundles.

             One way to distinguish smooth muscle from striated muscle is the absence of the regular pattern of sarcomeres (no A, I bands or Z lines).  Smooth muscle cells also have only one nucleus.  In that sense they are like cardiac muscle cells.   

            Smooth muscle cells can be distinguished from connective tissue by their organized appearance.  They are usually in a homogeneous bundle or sheet of cells rather than scattered single cells.  Fibroblasts, on the other hand, are scattered throughout the connective tissue in isolated groups.  The major challenge, however is distinguishing dense regular connective tissue from smooth muscle.  Use two identifying markers.  First, fibroblast nuclei are thin.  Second, smooth muscle nuclei are sometimes seen in a corkscrew shape which arises because they were contracted when they were fixed.             

 Where would you find smooth muscle?

             Smooth muscle cells are in sheets lining the walls of hollow organs.  For example, you can see rows of smooth muscle cells running circularly around blood vessels, especially prominent around muscular arteries.  Another good place to look is the wall of the gastrointestinal tract.  The smooth muscle cells may be organized in 2-3 layers.  One layer may run circularly around the lumen; another layer may be running longitudinally along the length of the organ. In the stomach, there is a layer that runs more diagonally or obliquely.  Each of these works together to propel food along the organ, or in the case of the stomach, churn the food.  Very small bundles are found attached to hair follicles.  These smooth muscle fibers “raise the hair on end” when we get goose bumps.

 Describe smooth muscle cell ultrastructure.

Smooth muscle cells have a region around the nucleus that is filled with some  smooth endoplasmic reticulum (SER) and lots of mitochondria.  The mitochondria provide the ATP needed for contraction.  The SER provides a site for calcium storage.  The remainder of the cytoplasm includes contractile filaments broken by focal densities.   The thin filaments are actin with tropomyosin.  No troponin is present in the smooth muscle cells.  What other calcium binding protein is found?   In addition, there are thick filaments that project the heavy meromyosin heads all along their length.  Thus, there is a larger surface area for  interaction of the myosin with the actin.  

 Focal densities, either in the cytoplasm or at the cell membrane are organizational sites for the thick and thin filaments (actin and myosin) to interact and be held in register.  Desmin or vimentin filaments also bind at these sites to help hold the filaments together.  These intermediate filaments help relay the contraction and help to shorten the cell.  The dense bodies also contain alpha actinin, an actin binding protein.  These dense bodies are similar to the Z lines of the striated muscle. 

                 The densities in the membrane are called adherent junctions.  Recall the same types of junctions are seen in epithelial cells. We called them “focal adhesions” or “zonula adherents”.  These provide attachment sites to the connective tissue outside the cell and also helping the muscle cells work together.  Actin was attached at these sites to actin binding proteins.  In the case of smooth muscle, alpha actinin is among the binding proteins.

                 Also, at the periphery are numerous invaginations of the plasma membrane, which are vesicular or saccular. These are called “caveolae” and are believed to help bring in calcium needed for contraction.  They are equivalent to the T- Tubule system in striated muscle.  They work with sarcoplasmic reticulum (smooth er) to sequester calcium when it is not needed for contraction.  They are shown in the following figure:

Vesicles (v) called caveolae are numerous at the periphery of smooth muscle cells.  These work like the T tubules, increasing the surface area for transfer of calcium into the cytoplasm.

 

The smooth endoplasmic reticulum is nearby. SER sequesters calcium and also releases it before the muscle contracts.

             Finally, smooth muscle cells are interconnected by ‘gap junctions’, which are specialized communication ports between the cells.  These are regions of many paired connexon molecules that work like molecular pores or channels running between the cells. Small molecules or ions can pass from cell to cell via these connexons and they provide communication links that regulate contraction of the entire bundle of smooth muscle.  

Gap Junction

 

This figure is a cartoon showing a connexon in register in two adjacent cells.  These are long, donut like molecules that allow passage of small molecules from one cell to another.  Examples of molecules that can pass include calcium ions, cAMP, ATP, etc.  Small molecules like fluorescein can also pass, which proves that cells have formed gap junctions

 How are smooth muscle cells structured to sustain the long wave like contractions?

             See your text for an important cartoon of this process.  The contraction process proceeds along the following steps.

 Step 1. Wave of depolarization along membrane from the neuromuscular junction or adjacent cells.

Step 2. Calcium is released from caveolae and endoplasmic reticulum

Step 3. Calcium binds to calmodulin

Step 4. Calcium-calmodulin complex activates and unfolds myosin light chain kinase

Step 5. ATP is used to phosphorylate myosin light chain kinase (this is unique to smooth muscle).

Step 6. Phosphorylated light chain kinase is activated so it can bind actin.

Step 7. Works like an ATPase to bind actin and move along the F actin chain.

 In short, (no pun intended) this works like the “sliding filament” to contract the muscle cells.  Intermediate filaments (desmin and vimentin) help with the contraction by pulling the cell ends in (shortening the cell).

The following cartoon shows this process.

The top view shows a relaxed smooth muscle cell.  Note the focal densities and the network of actin and myosin filaments.  

When contracted, the filaments slide together and pull the cell to a more rounded appearance.

 Sheets of smooth muscle cells work together because they are interconnected by gap junctions and connective tissue.

 

To stop the contraction:

Step 1. Reduction in calcium levels

Step 2. Calmodulin calcium complex dissociates

Step 3. Myosin light chain kinase is inactivated.

Step 4. Myosin phosphatase dephosphorylates the myosin light chain

Step 5. Actin binding site is masked

 

How is smooth muscle regulated?

             Smooth muscle can either receive innervation via the autonomic nervous system, or hormones through the blood system can regulate them.  Some muscle responds to both types of regulation.  Innervation involves nerve endings forming synapses with smooth muscle cells.  They are usually in the form of swellings of axons which contain synaptic vesicles (norepinephrine or acetylcholine are two neurotransmitters). An example of hormonal control would be found in the uterus, which is under the influence of oxytocin.  This would be active particularly during labor and delivery.

 What is the difference between single unit (unitary) or multiunit muscle groups.

             A multiunit system receives fine innervation allowing for regulation of individual cells.  The cells that control the opening of the iris are innervated individually.  A single unit (unitary) innervation pattern has a neuromuscular junction that serves a sheet or bundle of muscle fibers.   The cells that receive the stimulus in turn transmit it to other cells via the gap junctions (nexus).  Some muscle has both types of innervation patterns.

 How does the connective tissue sheath help organize smooth muscle function?

 Around each muscle cell is a fine connective tissue with reticular fibers.  This is called the “external lamina”. Smooth muscle cells are unique in that they produce the components of their extracellular matrix.  This anchors them together and also serves as a conduit for the contraction forces. The tension generated by contraction is transmitted to other cells, allowing the bundle to function as one unit. 

Describe myoepithelial cells and myofibroblasts and their functions.

             Just like their names suggest, myoepithelial cells or myofibroblasts are cells that have the properties of epithelial cells or fibroblasts, but they are also contractile. Myoepithelial cells can be seen around exocrine glands (such as sweat or mammary glands).  They form a basket like network of cells that squeeze the glandular cells to get the product into the duct.  Myoepithelial cells in the mammary gland are responsive to oxytocin and their actions produce “milk letdown”.  Myofibroblasts are like fibroblasts and cannot be distinguished with certainty. They are fairly inconspicuous in normal tissue.  After an injury, however, these specialized cells become active, proliferate and help repair the injured tissue.  They secrete collagen to form a scaffold over the wound and actually create the fibrous scar.  As healing progresses, the myofibroblasts use their contractile properties.  Each contracts to pull the extracellular matrix together to reduce the scar (damaged area).   A unique subset of stem cells can give rise to these myofibroblasts.  These are called “pericytes”. They lie around blood vessels and they will proliferate and form fibroblasts or myofibroblasts in areas of tissue injury.  They can support new tissue and blood vessels as they help repair the injury.

  Smooth muscle is involved in a number of disease states.  Here are some examples:

 During an asthma attack or an allergic reaction, the smooth muscle of bronchi contract and the airways narrow.  Drugs in inhalants that are actually smooth muscle relaxants can relieve this. 
 Myofibroblasts can actually be found in cases of fibrosis.  For example, in cirrhosis of the liver caused by too much drinking or drug use, or in fibrosis of the lung caused by too much smoking myofibroblasts proliferate.  In this case they are not playing a healthy role in the body.

 Lactation depends upon milk production by the mammary gland.  However, if the mother is not making enough oxytocin to stimulate myoepithelial cells, the milk will never get into the duct.  She may make enough milk, but it will not be able to be secreted because the myoepithelial cells cannot function.

 In atherosclerosis, one of the major problems is a build up of smooth muscle in the wall of the arteries.  There is an artificially induced proliferation of these cells and part of the narrowing of the arteries actually comes from smooth muscle cells that are accumulating in the area.

© text copyright, Gwen V. Childs, Ph.D. August, 2001
08/28/2001 date last edited
For questions:
childsgwenv@uams.edu
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gvchilds@cytochemistry.net
 
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