Smooth muscle physiology week 3 Flashcards Preview

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Flashcards in Smooth muscle physiology week 3 Deck (24):
1

Where in the body is smooth muscle found? 

walls of hollow internal organs, including all blood vessels except for capillaries, GI tract, bladder

2

What are the 3 functional roles of smooth muscle contraction?

1. propels contents through a hollow organ or tube

2. mantains pressure against the contents within a hollow organ or tube

3. regulates internal flow of contents by chaning radius to change resistance

3

What shape do smooth muscle cells have? How large are they in comparison to skeletal muscle cells? Do they have a T-tubule system? SR? How are they arranged?

Smooth muscle cells are spindle shaped and are much smaller than skeletal muscle cells. 2-10 microns in diamter and 50-400 microns long. Smooth muscle cells DO NOT have a T-tubule system. They do have a SR that is more poorly developed than in skeletal or cardiac muscle. Smooth muscle cells do not extend the entire length of the whole muscle (unlike skeletal muscle, but like in cardiac muscle cells so that when have room to stretch and increase force of contraction). Typically smooth muscle cells are arranged in sheets. 

4

How are the contractile and cytoskeletal elements of smooth muscle arranged in comparison to skeletal muscle? How do the individual contractile and cytoskeletal elements compare to those in skeletal muscle (thick filaments, etc)? What regulatory protein is not found in smooth muscle and what proteins are in its place?

Contractile and cytoskeletal elements are not arranged transversely as they are in striated muscle (have more of a diamond shap). Organization of its contractile apparatus is less well understood. 

Thick filaments: longer than those in skeletal muscle

Thin filaments: unlike skeletal and cardiac muscle, thin filaments DO NOT CONTAIN TROPONIN. Instead, they have calponin and caldesmon that are associated with thin filaments and serve regulatory roles. Thin filaments are more numerous in smooth muscle than in skeletal muscle. Also, thin filaments are longer than those of striated muscle. 

Intermediate filaments: not contractile elements but are a part of the cell's cytoskeleton and are probably responsible for some of the elastic properties of smooth muscle. 

These filaments are not organized into sarcomeres and smooth muscle does not have myofibrils.

5

What are dense bodies? dense areas?

dense bodies are analogous to Z-lines in striated muscle in that they anchor thin filaments and contain many of the same proteins found in Z-lines. Dense areas are essentially dense bodies associated with the sarcolemma and are involved in mechanical coupling btwn neighboring cells. 

6

On the basis of the electrical coupling btwn fibers, what are the 2 types of smooth muscle that can be identified? What are the properties of each? Which is more common? Where in the body is each found? How is each stimulated to contract?

single unit-smooth muscle: is the most common type. The fibers of single unit smooth muscle are electrically coupled by gap junctions so that they become excited and contract as a single unit. Single unit smooth muscle is sometimes called visceral smooth muscle because it is typical of visceral organs, including the walls of the 
gastrointestinal tract, the reproductive and urinary tracts and the smooth muscle of small blood vessels. Single-unit smooth muscle does not require nervous system 
stimulation to contract. Instead, it is self-excitable, with groups of fibers within single-unit smooth muscle producing spontaneous activity (although activity may often be modulated by the autonomic nervous system and other factors).

multi-unit smooth muscle: contains relatively few gap junctions. Thus at most only a small number of neighboring cells act as a unit. The multiple discrete units of this type of smooth muscle act independently and must be separately stimulated by nerves to contract. Multiunit smooth muscle is found in the walls of larger blood vessels, the iris of the eye, the airways of the lungs, and in the skin surrounding hair follicles.

Note that the distinction between single-unit and multi-unit smooth muscle is an over-simplification 
and becomes difficult to separate in some tissues.

7

What are the two types of smooth muscle contractions? (just list)

tonic smooth muscle contraction

phasic smooth muscle contraction

8

What is tonic muscle contraction? Where in the body is it typically seen? How is contraction maintained?

Tonic smooth muscles are muscles that are partially active all the time; examples include smooth muscle in the walls of most blood vessels, the airways of the lungs and various sphincters, all of which maintain a continuous level of partial contraction that is called tone.Tone (continuous partial contraction) of tonic smooth muscle is not associated with action potentials, although it is affected by membrane potential. Recent 
evidence indicates that in tonic smooth muscle resting tone is usually NOT dependent on elevated myoplasmic Ca2+ concentration.

Interpretation of attached graph:

Note that Ca2+ does not go back to basal levels during stimulation. As Ca2+ rises, phosphorylation increases and some level of phosphorylation is maintained. 
Contraction starts slowly and is maintained for some time.

9

What is phasic muscle contraction? Where in the body is it typically seen? How is contraction maintained?

Phasic smooth muscles: Muscles that do not maintain resting tone, but instead contract rhythmically or intermittently. Examples of phasic smooth muscle occur in the gastrointestinal, reproductive and urinary systems. Phasic smooth muscle usually produces action potentials; these either initiate contraction, or increase the contractile response. 

Interpretation of attached graph:

Respond to short duration stimulus. Note that Ca2+ goes back to basal level faster. Phosphorylation of cross bridges also goes back to basal levels faster and force is of shorter duration

10

How does Ca2+ enter smooth muscle cells to intiate contraction? How is Ca2+ released from the SR? How dependent is smooth muscle on Ca2+ release from the SR and why? How is smooth muscle tension graded as it relates to Ca2+?

As is the case in striated muscle, increased myoplasmic Ca2+ concentration is an important trigger for contraction in smooth muscle cells.Most of this Ca2+ enters from the extracellular fluid across the cell membrane through: Voltage-gated Ca2+ channels, ligand-gated Ca2+ channels, receptor-gated Ca2+ channels, stretch-activated Ca2+ channels.
Some Ca2+ is also released intracellularly from the SR; however, the SR in smooth muscle is relatively poorly developed (so it is not as dependent on SR Ca2+ release). The small diameter of smooth muscle cells makes diffusion from the surface to the center of the fiber a relatively fast process. Ca2+release from the SR can be either by Ca2+ induced Ca2+ release or via IP3 (with elevated levels due to the activation of G-protein coupled receptors). Smooth muscle tension can be graded by varying cytoplasmic [Ca2+] (just as in cardiac muscle).

11

What cellular events does Ca2+ initate to cause smooth muscle contraction? What is the "Ca2+ switch" (hint: the Ca2+ switch in skeletal muscle is Ca2+ binding to troponin).

How does the rate of cross-bridge cycling (and therefore length of contraction) compare to striated muscle and what is the reason for this?

How does the tension that smooth muscle can generate compare to skeletal muscle?

How does smooth muscle relax?

1. Ca2+ binds to calmodulin within smooth muscle fiber.

2. The Ca2+-calmodulin complex binds to and activates myosin light chain kinase (MLCK).

3. MLCK hydrolyzes ATP to phosphorylate myosin. Myosin is only able to bind to actin when it is phosphorylated!

4. Phosphorylated myosin binds to actin allowing cross-bridge cycling and contraction. 

Note that ATP is needed to dissolve cross-bridges just like in striated muscle. 

The process of cross-bridge cycling is generally much slower than in skeletal or cardiac muscle. Smooth muscle usually contracts and relaxes much more slowly than skeletal muscle, with single contractions lasting as long as several seconds. Myosin ATPase of smooth muscle splits ATP at a much slower rate than in skeletal muscle, resulting in slower cross-bridge cycling. Nevertheless, in comparison to skeletal muscle, smooth muscle is capable of generating as much (or more) tension per unit of cross sectional area.

Relaxation of smooth muscle is accomplished by moving Ca2+ back into the extracellular fluid across the surface membrane, and by active pumping of Ca2+ back into the SR (note there are autonomic effects that cause smooth muscle to relax: NO, epinephrine). Also, when Ca2+ concentrations are low, MLC phosphatase removes phosphate from myosin, therefore inactivating it.

 

12

How is the length-tension relationship in smooth muscle similar to and different than that of striated muscle? How is the major difference related to its functional role in the body? 

In a limited sense, the length-tension relationship for smooth muscle is qualitatively similar to that of skeletal and cardiac muscle, i.e., there is a range (relatively broad) of lengths where tension development is at or near its maximum. At both shorter and longer lengths active tension declines. However, smooth muscle is capable of shortening to about 1/2 of its ‘resting’ length 
and can still develop tension when it has beenstretched to about 2.5 times its resting length. Thus, smooth muscle can generate tension over a 5-fold variation in length. This can be contrasted with skeletal muscle, which normally operates only within 70-130% 
of its resting length.
The ability of smooth muscle to develop tension over this wide range of lengths is important to its functional role in the body. The hollow organs, which are surrounded by smooth muscle, can often vary in diameter a great deal (for example, consider the 
urinary bladder), yet smooth muscle remains able to generate active tension over the entire usual range of muscle fiber lengths.
 Because the contractile behavior of smooth muscle is so highly dependent on external influences, there is no meaningful and unique length-tension or force-velocity 
relationship for some types of smooth muscle in their physiological situation within the 
body.

13

What is the range of the resting potential of smooth muscle cells?

btwn -70 and -50 mV

14

Single-unit smooth muscle is electrically coupled by gap junctions. Gap junctions are much less common in multiunit smooth muscle. Many (but not all) types of single-unit smooth muscle are self-excitable, i.e., groups of 
specialized smooth muscle cells in this tissue generate spontaneous electrical activity that can then spread to other cells via gap junctions. What are the two types of spontaneous depolarization? (just list)

pacemaker activity

slow-wave potentials

15

How does pacemaker acitivity generate APs in smooth muscle? What ions are responsible for depolarization of the membrane?

In pacemaker activity, the membrane potential gradually and spontaenously changes due to shifting patterns of membrane permeability.  In many respects this is similar to pacemaker activity already described in the heart. When the membrane potential reaches threshold, an action potential is generated. After the action potential, the membrane potential once again begins to depolarize. The spontaneous depolarization results from the activation of a small cationic current (mostly Na+)

16

How do slow-wave potentials generate APs in smooth muscle? What ions are responsible for depolarization of the membrane?

 

Slow-wave potentials are alternating gradual hyperpolarizing and depolarizing swings of membrane potential that are thought to result from spontaneous cyclical changes in the rate of active transport of (in many cases) Na+ across the membrane. Slow wave potentials may or may not lead to action potentials. If the potential rises above threshold, bursts of several action potentials often result.

17

True or false: Not all smooth muscle cells generate action potentials. In any case, action potentials are not always required to generate contraction.

True.

18

True or false: Smooth muscle cells contain voltage-sensitive Ca2+ channels, which are opened by membrane depolarization. Some smooth muscle cells apparently also contain receptor-activated Ca2+ channels, which require binding of specific substances to receptors to open.

True. 

19

Describe the mechanisms by which contraction is iniated in each graph. 

Attached summarizes four ways in which smooth muscle cells can be excited to generate contraction. Not all cells utilize all of these mechanisms.
A: Triggered action potentials open voltage-sensitive Ca2+ channels in the cell membrane to generate slow summating tension.
B: Spontaneous potential changes can trigger action potentials, leading to contraction. Slow-wave activity is associated with action potentials.
C: Slow oscillations in potential (sometimes reflecting changes in the activity of electrogenic pumps) can cause changes in tonic contractile activity in the absence of action potentials.
D: Smooth muscle cells also show pharmacomechanical coupling in which changes of tension development are caused by drugs or hormones. Sometimes this can occur in the absence of significant changes in membrane potential.

20

What factors can modify the contractility of smooth muscle? 

drugs

hormones

local factors

autonomic innervation

21

How does autonomic innervation affect smooth muscle contraction? How does the synapse look (and how does it compare to skeletal muscle)?

Smooth muscle typically receives innervation from both the sympathetic and parasympathetic branches of the autonomic nervous system (there are exceptions: e.g., vascular smooth muscle generally receives only sympathetic innervation). For single-unit smooth muscle, such innervation does not normally initiate contraction, but it can modify both the rate of activity and the strength of contraction. Autonomic nervous system axons do not synapse with the single-unit smooth muscle cells in the way you are familiar with at the neuromuscular junction in skeletal muscle. Adrenergic and cholinergic receptors are dispersed over the entire surface of the smooth muscle cells. The postganglionic autonomic fibers travel across the surface of 
smooth muscle cells. Varicosities in the axon terminal release transmitter that diffuses to receptor sites on the muscle cells. Thus, smooth muscle cells can be 
influenced by more than one type of transmitter.

22

How do varicosities differ in multi-unit and single-unit smooth muscle? Why do these differences occur?

Please see slide 19 for more details

23

True or false: The stimulation of alpha and beta adrenergic receptors in vascular smooth muscle requires a change in the membrane potential.

False! Stimulation of these receptors to modify smooth muscle contraction is an example of pharmacomechanical coupling.

24

What are some other factors that influence the contraction of both single and multi-unit smooth muscle by changing the permeability of Ca2+ of the sarcolemma and/or the SR?