11/24/2014 Medical Physiology Smooth Muscle Eric Olson Flashcards
Smooth muscle has thin and thick filaments but lacks what?
Organized sarcomeres
In smooth muscle, the thin filaments are anchored to a cytoskeletal specialization called a _______
dense body
A smooth muscle twitch is characterized by slow contraction velocity and slow relaxation, and what kind of shortening?
Large amount of shortening, a smooth muscle cell can shorten to 1/3 its length.
T/F: Smooth muscle has t-tubules, but they are not organized as in skeletal muscle.
False. Smooth muscle has no t-tubules.
If smooth muscle has no t-tubules, how do impulses get transmitted?
Smooth muscle membranes contain indentations called caveoli which are in close proximity to the sarcoplasmic reticulum underneath the membrane surface. The caveoli also contain large numbers of important receptors and ion channels, like ACh receptors and Ca2+ channels.
Skeletal muscle APs are dependent on what ion, which is different from the ion that smooth muscle APs are dependent on. What are they?
Na+ - skeletal
Ca 2+ - smooth
Prolonged contractions in smooth muscle are known as:
tonic contractions
In a multiunit setup, smooth muscle has finer motor control. How?
Because electrical isolation can be attained, where bc the muscle cells are in slightly further proximity, impulses can propagate long distances.
Multiunit smooth muscle is known for discrete movements, as in the ciliary muscle of the iris, and piloerection in SNS response.
In a unitary smooth muscle setup, what kinds of junctions permit the transmission of electrical impulses?
Gap junctions
Unitary smooth muscle is known for coordinated movement as in peristalsis.
In most cases of smooth muscle contraction, how is Ca2+ released from the sarcoplasmic reticulum?
Ca2+ comes in through L type Ca2+ channels in the caveoli.
Explain the IP3 pathway for Ca2+ release.
Instead of coming in from the outside, a GPCR activates PLC, which splits into DAG and IP3, IP3 attaches to a Ca2+ channel in the SR and opens it, releasing Ca2+ into the cell.
A rudimentary sarcoplasmic reticulum in smooth muscle has two types of Ca2+ channels. What are their receptors?
Ca2+ (Calcium-induced Calcium releas)
IP3
Calcium is often removed from a smooth muscle cell after a contraction by a 3Na/Ca exchanger and pumps in the SR membrane and sarcolemma. Explain the less commonly understood method of “capacitative calcium entry”
Capacitative calcium entry occur when Ca enters the SR from outside of the cell, but apparently goes straight from the membrane to the SR membrane and does not induce a contraction.
T/F: Troponin C mediates smooth muscle contraction.
False: Troponin C mediates skeletal muscle contraction. In smooth muscle, contraction is mediated by the interaction between MLCK (and MLCP).
In smooth muscle contraction, Ca2+ binds to a _____ moiety on myosin light chain kinase (MLCK), resulting in phosphorylation of the regulatory light chain (RLC) of myosin. A conformational change in the RLC then permits the myosin to interact with actin.
Calmodulin
How does smooth muscle relax?
Myosin light chain phosphatase, locating in the sarcoplasm, dephosphorylates the RLC of myosin, the interaction between actin and myosin is blocked and the muscle relaxes.
Another route: reducing the amount of calcium in the cell.
Besides electromechanical APs, what is another cause of smooth muscle contraction?
Pharmacomechanical. Agonists can bind to GPCRs.
T/F: Phamracomechanical and electromechanical contraction both operate through increased cytosolic calcium and MLCK.
True
How does activation of vascular smooth muscle differ from that of intestinal etc. smooth muscle?
Peristaltic activity can be spontaneous, and coordinated with a pacemaker, as in the stomach. In vascular smooth muscle, contraction is in response to other factors, such as stretch, adrenergic neurons, endothelial cells or chemical factors.
The resting potential in smooth muscle is about ___1___ mV, which is ___2___ negative than in skeletal muscle.
- -50 to -60
2. 30 mV less
What is unique about uterine smooth muscle APs?
They are not spikes, as in unitary smooth muscle of the viscera. Uterine APs have plateaus.
What is the basal electric rhythm (BER)?
The BER refers to waves of rhythmic depolarization of intestinal smooth muscle cells, which originate at a specific point and are propagated along the length of the GI tract.
The pacemaker activity of the network of interstitual cells of Cajal in the stomach is not sufficient to produce coordinated contractions of the entire GI tract. How then is peristalsis accomplished?
Release of stimulatory NTs like acetylcholine from enteric nerve endings which are superimposed on the pacemaker waves.
T/F: The smooth muscle crossbridge cycle has an additional step, the latch state, which corresponds to tention with low ATP use.
True, tension can be maintained despite MLCP activity and low intracellular calcium.
How does the latch state in smooth muscle work?
It only works IF the MLCP acts on the myosin head while the myosin is still attached. The phosphate group is released from the myosin chain, but the myosin head detaches from the actin very slowly, maintaining tension. If the myosin head detaches from the actin first, and then the phosphate is released, then no latch state occurs.
What is ET-1?
Endothelin, a 21 amino acid protein that activates smooth muscle to constrict.
What stimulates endothelin formation and release?
Angiotensin II ADH thrombin cytokines reactive oxygen species shearing forces on the vascular endothelium
In addition to ETa and ETb receptors on smooth muscle, ETb is also found:
on the endothelium
What is different about the effects of endothelin on smooth muscle vs on the endothelium?
When endothelin binds to smooth muscle receptors, it causes smooth muscle constriction. When endothelin binds to receptors on the endothelium, NO is formed and this induces vasodilation **if no ET-1 receptors are present.
Because of its powerful vasoconstrictor properties, and its effects on intracellular calcium, ET-1 has been implicated in the pathogenesis of what conditions?
- HTN (pulmonary and systemic)
- Heart failure
- Coronary vasospasm
What is Bosentan?
An ET-1 receptor antagonist to treat pulmonary hypertension
ET-1 is release by what organ where it contributes to calcium overload and hypertrophy?
The failing myocardium
In the fight or flight response, adrenaline released from the __1__ circulates in the blood and causes __2__ in most arterioles, for example skin and gut, while causing __3__ in the arterioles of skeletal muscle and heart, as well as the bronchiolar smooth muscle in the lung. This diverts blood flow and oxygen to the skeletal muscles and heart, and opens the airways in preparation for __4__.
- Adrenal medulla
- Vasoconstriction
- Vasodilation
- physical exertion
How can one agonist such as epinephrine (adrenalin) in the blood cause opposite responses in skin and muscle arterioles?
Two different kinds of receptors, alpha-1 and beta-2.
The binding of epinephrine to alpha-1 receptors leads to:
vasoconstriction
The binding of epinephrine to what receptor leads to vasodilation?
Beta-2
Beta-2 receptors act via Gs GPCR to stimulate what?
Adenylate cyclase (AC), which produces cAMP and activates PKA inactivates MLCK by phosphorylating it.
By phosphorylating MLCK, what effect occurs in the muscle?
MLCK-phosphate is inactive, therefore MLCK cannot be activated by Ca2+ and calmodulin, therefore no myosin phosphorylation, therefore muscle contraction, therefore relaxation.
Where are beta-2 receptors primarily found?
Heart and skeletal muscle arterioles
Endothelin is the most potent known endogenous vasoconstrictor and is secreted by:
vascular endothelial cells
Give some examples of when oxygen availability is decreased.
- CO poisoning
2 Cyanide poisoning - High altitude
- Pneumonia
When oxygen availability to tissues is decreased, what happens to blood flow?
Increases markedly. At 25% O2 sat, Blood flow is 3x normal, though even this mechanism cannot compensate for the lack of oxygen.
What is hyperemia?
Increased blood flow to an area
Active hyperemia in skeletal muscle can increase local blood flow as much as ???? during intense exercise.
20-fold
Name some local vasodilators possibly involved in hyperemia.
Adenosine CO2 Adenosine-phosphate compounds Histamine K+ ions H+ ions
What are the two main theories behind hyperemia?
- Lack of O2 leads to smooth muscle relaxation of the sphincter
- Vasodilator chemicals, ie adenosine, are released by active muscle to cause relaxation of the sphincter.
Adenosine binds what receptors in vascular smooth muscle?
A1, A2A and A2B GPCRs (no adrenergic receptors)
Adenosine receptors are thought to act in two ways. In the first way, A2 adenosine receptors can couple to Gs leading to AC stimulation and an increase in cAMP and PKA activity. What effect does elevated PKA have?
Elevated PKA activity is associated with vascular smooth muscle relaxation.
How might K+ channels coupled to A1 adenosine receptors cause smooth muscle relaxation?
If K+ channels open, the cell can become hyperpolarized, therefore leading to a decrease in calcium influx.
What is “stress relaxation?”
Passive decline in tension over time during which there is constant volume or length change, as in the aorta or the bladder. it is related to the elastic properties of the tissue, like collagen and elastin content.
What is “receptive relaxation?”
The ability of the stomach to relax as its volume increases. It results in a drop in gastric pressure immediately after eating that persists until food has passed into the small intestine. Signals can also be sent by a stretched duodenum (CCK).
What chemical signals are involved in receptive relaxation?
- ACh released by vagal pathways
2. VIP (vasoactive intestinal peptide) and NO
NO is released by what two sources in smooth muscle relaxation?
- Autonomic neurons
2. Endothelial cells that lines the blood vessel
Take a moment to redraw the table on page 184 in the printed notes.
This is not a joke. Redraw this important table on muscle.
