L14 Smooth Muscle Flashcards
Where is smooth muscle found?
In the walls of hollow organs and tubes such as:
- arteries and veins
- trachea and bronchioles
- GI tract
- uterus
- bladder
- ureters
- iris of the eye
Smooth muscle helps organs maintain their shape. What are three other functions of smooth muscle?
produces motility through the hollow organ or tube (ie. chyme through GI, urine through ureter)
maintains pressure against the contents within the hollow organ (ie. blood vessels)
regulates internal flow of contents by changing tube diameter (provides resistance)
What controls smooth muscle tone, contraction and relaxation?
ANS, hormones, other local paracrine agents
What is the structure of smooth muscle?
No striations, no t-tubules
filaments do not form myofibrils
not arranged in sarcomere pattern found in skeletal muscle
less developed sarcoplasmic reticulum, but in contact with the plasma membrane
contain dense bodies which anchor actin and myosin filament
spindle-shaped cells with single nucleus
Have caveolae: membrane lipid rafts that profice means for extracellular communication
What are the two arrangements of cells into sheets within smooth muscle?
circumferential (eg. small arterioles, for vasoconstriction)
longitudinally (eg. small intestine, both arrangements for peristalsis)
What kind of junctions does smooth muscle have and why?
gap junctions to electrically couple cells
adjacent cells linked by small connecting tunnels formed by connexons
this allows for full recruitment: cells function as a syncytium and are connected anatomically and electrically
found in single-unit smooth and cardiac muscle
conducts ions like Ca2+
What are the three types of smooth muscle?
multi-unit: not electrically coupled, electrical isolation of cells allow finer motor control
single-unit: electrically coupled via gap junctions, gap junctions permit coordinated contraction
vascular smooth muscle: combination of unitary and multiunit smooth muscle
What are 3 types of filaments in smooth muscle?
thick myosin filaments: longer than those in skeletal muscle
thin actin filaments: contain tropomyosin but not troponin
dense bodies: attachment for actin filaments, can also be attached to cell membrane, serve same role as Z disks in skeletal muscle
Explain multiunit smooth muscle
neurogenic (nerve-produced)
consists of discrete units that function independently of one another (similar to skeletal muscle)
units must be separately stimulated by nerves
Found in: ciliary muscles of eye lens, iris of the eye, skin piloerector muscle, walls of large blood vessels, small airways of lungs, vas deferens
Explain single-unit smooth muscle (also called visceral smooth muscle).
myogenic (self-excitable)
does not require nervous stimulation for contraction, slow spontaneous waves
fibers become excited and contract as a single unit because cells are linked electronically by gap junctions: functional syncytium
contraction is slow and energy efficient, well suited for forming walls of distensible, hollow organs
Found in: GI tract, bladder, small blood vessels, uterus and ureter
What is the resting membrane potential of smooth muscle cells?
Explain what affects action potentials.
resting membrane potential is not constant, but variable, ranging from -65mV to -45mV
action potential is Ca2+ dependent, rather than Na+ dependent. only unitary smooth muscle cells generate action potentials
multi-unit smooth muscle cells do not fire action potentials
Some unitary smooth muscle is self-excitatory and can elicit spontaneous depolarization of the resting membrane potential. Name two ways in which this happens.
pacemaker potentials: membrane potential gradually depolarizes until it reaches threshold for action potential
slow wave potentials: membrane potential alternatively depolarizes and hyperpolarizes (oscillates). When threshold is reached, the cell fires a burst of action potentials.
What are three types of unitary smooth muscle action potentials?
spike potential: typical action potential of unitary smooth muscle cells. Depolarization phase in due to voltage-gated Ca2+ channels
action potential with “plateau”: repolarization is delayed allowing for prolonged contraction. typical in ureter, uterus, and certain vascular smooth muscle cells
slow wave potentials: spontaneous depolarization of the resting membrane potential in unitary smooth muscle cells. typical slow wave rhythm in visceral smooth muscle cells
How is smooth muscle different from skeletal muscle?
smooth muscle does not have sarcomeres or t-tubules, and contains fewer sarcoplasmic reticulum
smooth muscle has actin and myosin but does not contain troponin
unlike skeletal muscle, regulation of crossbridge cycling in smooth muscle occures on the thick myosin filament by lightweight proteins attached to the myosin molecules
How does smooth muscle contract?
intracellular Ca2+ concentration increases when Ca2+ enters the cell through Ca2+ channels in the cell membrane or SR
Ca2+ binds to calmodulin in the cytosol to form Ca2+-calmodulin complex, which binds to and activates myosin light chain kinase (MLCK)
MLCK phosphorylates the myosin light chain (MLC) cross-bridges, enhancing their ATPas activity leading to interaction with actin and contraction of smooth muscle. cross-bridge cycle produces tension and shortening
when Ca2+ concentration decreases due to pumping of Ca out of the cell, the process is reversed and myosin light chain phosphatase (MLCP) removes the phosphate from MLC, dephosphorylated myosin cross-bridges cannot bind to actin filaments, and relaxation occurs
How does the calcium activation of myosin cross-bridge in smooth muscle work?
Compare the role of calcium in smooth and skeletal muscle contraction.
How is contraction of smooth muscle thick filament regulated?
increased intracellular Ca2+ concentration phosphorylates myosin and promotes contraction
phosphorylated myosin binds actin
pulls thin filaments towards center of myosin
ratchet action
decreased intracellular Ca2+ concentration dephosphorylates myosin and promotes relaxation
Explain generally some mechanisms for increasing intracellular Ca2+ concentration in smooth muscle. How does this contrast with skeletal muscle?
From the ECF via sarcolemma voltage gated Ca2+ channels that are opened by depolarization
Through ligand-gated channels in the sarcolemmal membrance
Released by SR by IP3-gated mechanisms or Ca2+ induced Ca2+ released (RyR)
This is different in skeletal muscle in which the rise in intracellular Ca2+ is caused exclusively by depolarization induced release from the SR.
How does intracellular Ca2+ concentration increase via voltage-gated Ca2+ channels?
These channels are located in the sarcolemma and open when the cell membrane potential depolarizes
Both subthreshold depolarizations or action potentials in smooth muscle cell membrane cause voltage-gated channels to open, allowing calcium to flow into the cell down its electrochemical potential gradient
This mechanism not present in multi-unit smooth muscle
How does intracellular Ca2+ concentration increase via IP3-gated sarcoplasmic reticulum Ca2+ channels?
These channels are opened by hormones and neurotransmitters. While the process begins at the cell membrane, the source of calcium is the SR rather than the ECF
Hormones or neurotransmitters interact with specific receptors on the sarcolemma membrane which are coupled via a G protein to PLC
Phospholipase C catalyzes the hydrolysis of PIP2 to IP3 and DAG
IP3 then diffuses to SR where it opens the calcium release channels and calcium flows from its storage site in the SR into the ICF
How does intracellular Ca2+ concentration increase via ligand-gated Ca2+ channels?
These channels are present in the sarcolemma and are not regulated by membrane potential, but by receptor-mediated events
Various hormones and neurotransmitters interact with specific receptors in the sarcolemma membrance that are couple to the Ca2+ channels by a GTP binding protein
How does intracellular Ca2+ concentration increase via Ca2+-induced Ca2+ release sarcoplasmic reticulum channels (CICR)?
These channels are similar to ryanodine receptors (RYR) in skeletal and cardiac muscle and are opened after a rise in cytoplasmic Ca2+
The levels of cytoplasmic Ca2+ necessary to operate these channels are much higher than those that typically occur under physiological conditions, therefore their rold in regular contractility remains unclear
What are some mechanisms for decreasing intracellular Ca2+ concentrations in smooth muscle?
A decrease in contractile force occurs when the concentration of intracellular calcium decreases
cytosolic calcium concentrations may decrease by: return of calcium into the SR by SR Ca2+ ATPase (SERCA)
Extrusion of calcium from the smooth muscle cell by:
- Sarcolemmal Na+/Ca2+ exchanger: energy for the extrusion of calcium against its concentration gradient is from the inward driving force for Na+. Na+/K+ maintains the Na+ gradient
- Sarcolemmal Ca2+ ATPase: actively pumps Ca2+ out
Explain gradation of contraction.
Ca2+ promotes actin-myosin interaction by stimulating myosin phosphorylation
A single excitation in smooth muscle does not cause all the cross-bridges to switch on (in contrast to skeletal muscle)
As Ca2+ concentration increases, more cross-bridges are brought into play and greater tension develops
Explain how smooth muscle ANS muscarinic receptors work.
Muscarinic M2: located in myocardium, smooth muscle
- opening of K+ channels, inhibition of adenylyl cyclase, decrease cAMP
Muscarinic M3: located in exocrine glands, endothelium, smooth muscle
- formatino of IP3 and DAG, increase in intracellular Ca2+
Explain how smooth muscle adrenergic receptors work.
Adrenergic alpha1: smooth muscle
- formation of IP3 and DAG, increase in intracellular Ca2+
Adrenergic alpha2: smooth muscle, presynaptic sites, platelets
- inhibition of adenylyl cyclase, decrease cAMP
Adrenergic beta2: myocardium, smooth muscle
- stimulation of adenylyl cyclase, increase cAMP
How is smooth muscle tone regulated?
By Ca2+ infux into cells via voltage-gated Ca2+ channels
- Directly block voltage-gated Ca2+ channels
- Open K+ channels to hyperpolarize the cell and result in closure of voltage-gated Ca2+ channels
What do calcium antagonists do?
Block voltage-gated Ca2+ channels
These drugs reduce calcium influx and calcium-induced calcium release acting as vasodilators
Examples: nifedipine, verapamil, diltiazem
What do potassium channel openers do?
Cause hyperpolarization of smooth muscle cells that promotes relaxation of smooth muscle
These drugs act as vasodilators
Example: pinacidil
What is an alternative to decrease smooth muscle tone involving cAMP?
cAMP: relaxes smooth muscle by inhibiting the MLCK even in the presence of increase intracellular Ca2+
Example: albuterol for asthma
beta2 adrenergic receptors agonist that stimulates cAMP prouduction from adenylate cyclase
What is an alternative to decrease smooth muscle tone involving cGMP?
cGMP: relaexes smooth muscle by activating myosin phosphatase resulting in myosin dephosphorylation
- Stimulate cGMP production. Works on endothelial cells to produce nitric oxide which stimulates cGMP production on smooth muscle. Example: nitroglycerin- high coronary blood flow
- Inhibit cGMP degredation by phosphodiesterase. Phosphodiesterase inhibitor that prevents cGMP degredation. Example: Sildenafil-erectile dysfunction
