Lecture 2: Smooth Muscle Physiology Flashcards
Histological appearance of skeletal muscle.
Large, multi-nucleated striated cells
Histological appearance of smooth muscle.
Smaller, single nucleus cells with NO striations
Sarcoplasmic reticulum of skeletal muscle
Large, WELL-developed SR with triads
Sarcoplasmic reticulum of smooth muscle
Poorly developed SR
Thin filament components of skeletal muscle
Actin, Tropomyosin, and troponin
Thin filament components of smooth muscle
Actin and Tropomyosin
Thick filament composition of skeletal muscle
Myosin with ATPase (faster activity)
Thick filament composition of smooth muscle
Myosin with ATPase (slow); myosin light chains
Which type of muscle contains more thin filaments; thick filaments?
- Smooth = MORE thin (2x more)
- Skeletal = MORE thick (4x more)
As skeletal muscle is stretched, what happens to the ability to generate tension (force)?
Increased stretching = Decreased tension (force)
What 5 important functions must the muscle of the gut, vasculature, and respiratory tract be able to do?
1) Contract and maintain contraction for long period of time (energy efficient)
2) Contract periodically to mix contents of organ
3) Maintain shape of organ
4) Generate active tension even when stretched
5) Use relatively little ATP
Where is smooth muscle found?
1) Vasculature (arteries in particular)
2) GI tract
3) Urogenital tract
4) Respiratory tract
5) Eye
Where do the thin filaments of smooth muscle anchor?
Dense bodies
What do the different isoforms of myosin in smooth muscle contain?
- Myosin light chain kinase
- Myosin light chain phosphatase
Is all smooth muscle the same?
No, because the needs are different based on where yo find smooth muscle, there ARE different types (although contractile mechanism is the same)
Where would you find smooth muscle with lots of gap junctions?
- The gut
- Contraction is well coordinated
Where would you find more autonomous smooth muscle with less gap junctions?
- Vasculature (arteries in particular)
Skeletal muscle is innervated by; using what neurotransmitter?
- Alpha-motorneurons arising from spinal cord
- Acetylcholine
Intrinsic innervation of smooth muscle uses; is independent of?
- Neurons (sensory and motor)
- Independent of CNS and PNS
What controls extrinsic innervation of smooth muscle; importance?
- The autonomic nervous system
- Allows CNS to control viscera
How does acetylcholine act on smooth muscle?
- Excites SOME smooth muscle (gut)
- May inhibit others (cause relaxation)
Norepi and epinephrine cause ______ of vascular smooth muscle?
Contraction
Norepi and epinephrine cause ______ of gut smooth muscle?
Inhibition
What neurotransmitter is the major inhibitor of smooth muscle?
Nitric Oxide (NO)
NO acts via what kind of mechanism?
cGMP mechanism
What is one of the major differences between skeletal and smooth muscle as far as neural control goes?
Smooth muscle CAN be DIRECTLY INHIBITED (caused to relax)
Where is neurotransmitter released from in smooth muscle?
Varicosities - swellings in the axon
Skeletal muscle has only _______receptors for contraction?
Ach receptors
NO does not require a membrane-bound receptor why?
Extremely lipid soluble; diffuses through cell membrane and has its action on the cGMP system
Which 3 hormones are able to elicit smooth muscle contraction?
1) Acetylcholine
2) Epinephrine
3) Cholecystokinin (CCK)
Another name for NO is?
Endothelium-derived relaxing factor (EDRF)
Which agent can be released as both a NT and through paracrine mechanisms?
- NO
Stretching of some smooth muscle does what?
Another mechanism for activation
What are the receptor types for skeletal muscle?
Nicotinic cholinergic
What are the receptor types for smooth muscle?
Muscarinic cholinergic; Adrenergic, others
What are the 2 sources of Ca2+ for smooth muscle contraction?
1) Sarcoplasmic reticulum
2) Extracellular sources
The SR and Extracellular sources of Ca2+ are regulated ________ of one another.
Independently
The binding of a hormone to a GPCR and subsequent activation of IP3 causes what in smooth muscles?
The release of Ca2+ from the SR
What else is activated upon the creation of IP3 in smooth muscle?
PKC
Why is the mechanism of using IP3 to release Ca2+ from the SR significant?
Smooth muscle can be activated to contract in the absence of an action potential
What are the two type of channels for extracellular Ca2+ sources in smooth muscle?
1) Voltage-gated Ca++ channels
2) Ligand-gated Ca++ channels
What is the importance of extracellular sources of Ca2+ in smooth muscle?
Allows for sustained contractions of smooth muscle
What must occur for the myosin-ADP*Pi of smooth muscle to increase its affinity for the actin binding site?
Phosphorylation of the myosin light chain
What’s step 1 for smooth muscle contraction?
Increase the intracellular calcium
What occurs during step 2 of smooth muscle contraction?
Calcium will bind with Calmodulin
What occurs during step 3 of smooth muscle contraction?
Calmodulin activates myosin light-chain kinase (MLCK)
What occurs during step 4 of smooth muscle contraction?
MLCK phosphorylates the myosin light chain
How does MLCK phosphorylate the myosin light chain?
Hydrolyzes a separate ATP —> ADP + Pi
How many ATP are being used in smooth muscle contraction; location?
2 separate ATP; one on the light chain, and one on the myosin head
What’s step 5 of of smooth muscle contraction?
Myosin cross bridge can begin cycle
What occurs after the myosin forms a cross bridge with the actin binding site?
ADP + Pi will be released from the myosin head. A conformational change occurs and the power stroke is initiated
The myosin head will stay bound to the actin binding site until?
An ATP comes in and binds to the myosin head proper, the myosin head will then dissociate back to the low affinity state
During smooth muscle relaxation where is the calcium pumped and why?
Outside of the cell, because that is where most of it came from.
What occurs once the calcium is taken off the calmodulin?
Calmodulin will inactivate the MLCK and we see the formation of a myosin light-chain phosphatase, which will remove the Pi from the myosin light chain and allow relaxation.
The Pi can be removed from the myosin light chain at any point in the cycle - the cycle will then continue _______ and a new cycle ________. (latch mechanism)
- Very slowly
- Cannot be started
What occurs during the latch mechanism?
- Dephosphorylation of the MLCK during cycle - slows cycle, especially at the binding of ATP (very slow).
- Cross-bridges remain stuck (and therefore generating tension) for prolonged period of time
With every stretch of smooth muscle cells what occurs with passive tension?
Increases a little, but as actin and myosin rearrange, the passive tension decreases again
How are the thick and thin filaments arranged in smooth muscle?
Randomly! With far more thin filaments
As smooth muscle is stretched, the myosin heads, once free from the actin, will interact with?
A DIFFERENT thin filament
The “loose” arrangement of the thick and thin filaments allows them to ________ when the cell is stretched
Re-arrange
The rearrangement of thick and thin filaments in smooth muscle allows for?
Passive tension to dissipate
Why is the rearrangement in smooth muscle important for active tension?
Allows the cell to continue to develop active tension over a much wider range of lengths than we see in skeletal muscle
Damage to blood vessels causes chemical signals to be released, which trigger smooth muscle to do what?
De-differentiate into fibroblasts
Why is the de-differentiation of smooth muscle into fibroblasts important during injury?
Fibroblasts secrete the collagen needed to repair the damage
What occurs to the fibroblasts once the damage is resolved?
They differentiate back into the smooth muscle cells required to make the blood vessel work properly
What is the de-differentiation and differentiation of smooth muscle referred to as?
Plasticity
Why is it crucial that smooth muscle can be intrinsically innervated independently of the CNS and PNS; paraplegic example?
In someone like a paraplegic, if the smooth muscle didn’t have intrinsic innervation they would not be able to do any kind of digestion
