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69 Cards in this Set

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What is the main difference between smooth and skeletal muscle?
Their structure - Smooth is much less uniform in appearance and is not striated
What are the 2 types of classification of smooth muscle?
1. Single unit
2. Multi unit
How does single unit smooth muscle contract?
As a unit, all together; each muscle fiber doesn't have its own innervation
How does multi-unit smooth muscle contract?
Each muscle fiber is individual and not electrically connected to its neighbors
What is the prominent difference in how single unit vs multi unit muscle contracts?
Single unit = spontaneous
Multi unit = not spontaneous; it requires excitation
What is an example of
-Single unit
-Multi unit
Single unit = intestinal

Multi unit = Aorta
Are all blood vessels multi unit smooth muscle?
No; small arters are single unit smooth muscle
How does the smooth muscle microstructure compare to skeletal?
-Both have Actin and myosin present
-Smooth has no striations
-Smooth has dense bodies
What are the dense bodies in smooth muscle analogous to in skeletal muscle?
The z-lines
What molecules link Dense bodies in smooth muscle? Why?
Desmin and Vimentin - to provide a scaffold for smooth muscle and link the dense bodies together.
How are thick and thin filaments in smooth muscle arranged?
They're interdigitated like in skeletal muscle striations, but not as orderly and uniformly.
What is the ratio of thin:thick filaments in cardiac and skeletal muscle?
2 thin : 1 thick
What is the ratio of thin:thick filaments in smooth muscle?
15:1 - because the thin filaments are extremely long and there's a lot more of them; this is necessary to generate tremendous changes in the overal length of the muscle cell during contraction.
What are the thick filaments in smooth muscle composed of?
Myosin
What re the thin filaments in smooth muscle composed of? What don't they have?
-Composed of Actin, Tropomyosin, Caldesmon and Calponin
-Don't have troponin
So what do we know DOESN'T stimulate smooth muscle contraction?
Calcium binding to troponin-c
Where are Caldesmon and Calponin located? What do they do?
-Bound to thin filaments
-Inhibit myosin ATPase activity sterically
Where is the control of smooth muscle contraction centered?
On the myosin component of the THICK filament
What is the basic structure of myosin like in smooth muscle?
Same as in skeletal muscle, but a different isoform of myosin ATPase
What is the myosin molecule structure like?
-2 heavy chains
-4 light chains
What are the 2 types of light chains?
-2 essential
-2 regulatory
Why are the regulatory light chains important in smooth muscle?
They are crucial because they cause contraction when calcium levels reach a threshold.
What is absolutely necessary for smooth muscle contraction to occur?
Calcium
What is the molecule that activates cross bridge formation in smooth muscle?
MLCK
What terminates cross bridge cycling and contraction?
MLCPhosphatase
What happens when MLCK is active?
It phosphorylates the regulatory light chains on myosin, so it can start hydrolyzing ATP and contraction ensues.
What is the intermediate molecule that links Ca levels reaching threshold to activation of MLCK?
Calmodulin
How does the calcium-calmodulin complex activate MLCK?
By exposing its catalytic domain which enables MLCK to transfer a phosphate from ATP to myosin's regulatory light chain
What is the direct result of regulatory light chain phosphorylation?
Myosin's ATPase activity is awakened and crossbridge cycling.
What does the velocity of contraction of smooth muscle correlate with?
The degree of phosphorylation of the myosin regulatory light chain - EARLY in the contraction.
What DOESN'T the degree of phosphorylation of myosin light chain correlate with?
It does NOT correlate with the amount of FORCE maintained.
How can we tell that the degree of phosphorylation correlates with the shortening velocity but not the degree of maintained force?
Because as time goes on, MLCP starts to dephosphorylate the reg light chain, which reduces the amount of phosphorylation.
What are the 3 important features of the latch stte?
-Maintained force
-Low cycling rate
-Low metabolic rate
What allows for the latch state?
Maintained elevated calcium levels during slow cycling.
What is the main result of the smooth muscle latch state?
More heads are attached because there is very slow cross bridge cycling.
What is the function of the latch state?
To allow smooth muscle surrounding the gut for example to maintain a high force for a long time w/out a lot of energy expenditure
What molecule is crucial for cessation of crossbridge formation?
MLCP
What is the resting membrane potential of smooth muscle? Skeletal muscle?
Smooth = -40 mV
Skeletal = -70 mV
SMOOTH IS MUCH LESS NEGATIVE
Why is the resting Em of smooth muscle so much more positive than for skeletal muscle?
Because the potassium conductance is much lower
How much can the smooth muscle Em fluctuate?
A lot depending on the muscle type - may be steady, or show spontaneous oscillations / APs
What is the resting Em of smooth muscle close to? Why?
The viscinity of the range of potentials where calcium channels are open and closed; allows fine control of the muscle.
What is the role of the Em in regulating contractile force of smooth muscle?
-Depolarization causes contraction
-Hyperpolarization causes relaxation
What are the changes in Em that regulate contraction of smooth muscle like?
Graded - no
Can changes in contractile force of smooth muscle occur WITHOUT changes in membrane potential?
Yes - this is Pharmacomechanical coupling
Does pharmacomechanical coupling occur under normal conditions?
No
Define pharmacomechanical couping one more time:
Changes in force without changes in membrane potential
What is the most common mechanism of pharmacomechanical coupling? How is it done?
Changes in contractile filament calcium sensitivity; done by just increasing the permeability of the cell to calcium.
What membrane receptor and enzyme can increase calcium in the cell and increase contractile force independent of Em?
Phospholipase C cleaving of IP3 to induce calcium release
What special ion channels open and minimize changes in Em by hyperpolarizing the cell during contraction?
Calcium - activated Potassium channels
What is the most important and common type of pharmacomechanical coupling?
Changes in contractile filament calcium sensitivity (just by increased intracellular calcium)
What is more important; electricomechanical or pharmacomechanical coupling?
Electromechanical coupling - changes in the resting Em.
How does the resting membrane potentail of smooth muscle change as intracellular K increases?
It becomes more positive
So why is the resting Em of smooth muscle so positive?
Because there is less potassium conductance (less efflux) so the cell is more positive.
What are 3 types of electrophysiological responses that can be seen in smooth muscle?
1. Graded changes in Em
2. Action potentials
3. Slow oscillations in Em
In what type of smooth muscle are APs characteristic?
Unitary (single unit) - intestinal
What ion causes APs in smooth muscle?
Calcium
What ion does NOT contribute to action potentials in smooth muscle? Why not?
Sodium - becuase there ARE NO FAST SODIUM CHANNELS in smooth muscle (no TTX sensitive channels)
What does the calcium influx during ca-dependent AP's in smooth muscle directly influence?
Excitation contraction coupling - the same calcium that causes the AP also causes contraction via Ca/Calmodulin stim of MLCK
What makes the APs in unitary smooth muscle unique?
They can be spontaneous - not dependent on higher motor nerve input.
What allows for APs to spread throughout intestinal muscle and coordinate their contraction?
Low-resistance gap junctions
What happens in smooth muscle when oscillations of the Em reach threshold?
Voltage-gated calcium channels open
What is the result of Calcium influx due to voltage-gated calcium channels opening?
Depolarization and generation of an AP spike
What is the Calcium that causes the AP also responsible for?
Excitation-contraction coupling
What is the result of calcium levels rising inside the smooth muscle cell?
Opening of Ca-dependent K channels
What happens as smooth muscle internal K rises?
It hyperpolarizes the cell
What happens as a result of smooth muscle hyperpolarization?
Voltage-gated Ca channels close
What happens as internal calcium goes down?
Ca-dependent K channels close
What happens when K channels close in smooth muscle?
The cell then depolarizes and calcium can influx again.
So what symptom results from hypercalcemia due to its effect on intestinal smooth muscle?
Constipation