L9: Physiology of Smooth Muscle Flashcards
1
Q
Describe distinguishing characteristics of multi-unit and unitary smooth muscle
A
- Multi-unit: discrete fibers that contract independently as each is innervated by the ANS, no communication with neighboring fibers through gap junctions. Found in ciliary, iris muscles and piloerector muscle
- Unitary: group of fibers that contract together, arranged in sheets/bundles, regulated by both ANS and non-neuronal (hormones/metabolites), specific points of innervation with communication between fibers via gap junctions. Found in GI, bile ducts, ureters, uterus and BVs
2
Q
Compare and contrast contractile components (structural) utilized in smooth muscle and skeletal muscle
A
- Both contain actin, myosin and tropomyosin
- No troponin in SM, only in SkM
- Myosin differs in SM as heads are arranged in different directions
- Dense bodies are similar to Z-disks, and allow for force of contraction to be transmitted from one cell to next and also serves as anchoring point for actin
- Myosin is dispersed between actin, these slide over each other via contraction, but d/t dense bodies and arrangement of these proteins, contraction results in shrinking and bulging of cell
3
Q
Compare and contrast actomyosin regulation of smooth and skeletal muscle contraction
A
- Skeletal muscle: calcium binds TnC allows for tropomyosin to uncover myosin binding site on actin and myosin binds to actin if myosin is bound to hydrolyzed ATP (ADP-Pi). Does not require phosphorylation at regulator site (if there is one??) When calcium drops and is pumped back into SR, tropomyosin recovers myosin binding site and prevents any further cross-bridge formation, thus relaxation.
- Smooth muscle: calcium binds calmodulin and this complex activates myosin-light chain kinase (MLCK), which uses ATP to phosphorylate myosin’s regulator site. This increases myosin head ATPase function and ATP bound to myosin is hydrolyzed to ADP-Pi form and now myosin and actin can interact. Decrease in calcium will decrease MLCK activity and prevent regulator site from being phosphorylated. Thus decreasing myosin head ATPase activity and preventing cross-bridge formation. In addition, a myosin phosphatase can remove phosphate from regulator site. Relaxation results.
4
Q
Describe the sequence of intracellular events that control contraction and relaxation of smooth muscle
A
- ) Contraction:
- Calcium binds to calmodulin. This complex activates myosin ligh-chain kinase (MLCK) and phosphorylates regulator chain of myosin.
- When myosin is phosphorylated at regulator site and head is bound to ADP-Pi (hydrolyzed form of ATP), myosin cross-bridges with actin
- Release of ADP-Pi from head causes power stroke (Pi still bound to regulator site)
- ATP now binds myosin head and releases myosin from actin
- Hydrolysis occurs and cross-bridge can reform (as above) provided regulatory unit is phosphorylated, thus two molecules of ATP required - ) Relaxation:
- Decrease in calcium leads to a decrease in MLCK activation and phosphorylation of regulator site on myosin and decrease in myosin head ATPase activity.
- Relaxation state = myosin not phosphorylated at regulatory site and decrease in ATPase activity by myosin head, so no cross-bridge formation.
- This process can also be regulated via myosin phosphatase, which cleaves phosphate group from myosin regulatory site
5
Q
What is the “latch state” seen in smooth muscle?
A
- Form that allows for persistent contraction with low energy requirements. Once actin-myosin cross-bridge forms, dephosphorylation of regulatory site can occur. Results in reduced ATPase activity and very “slow” power stroke causing bridge to be maintained for relatively long period and therefore tonic contraction
6
Q
Describe the structural differences in neuronal innervation between smooth and skeletal muscle
A
- No structured NMJs in smooth muscle like in SkM. Diffuse branches of nerve fibers in sheets over smooth muscle. Varicosities seen in SM where NTs are released. Nerve fiber in most cases doesn’t contact SM (diffuse junction), in some cases it does (contact junction as seen in multi-unit SM).
7
Q
Neuronal and non-neuronal regulators of smooth muscle contraction
A
- Neuronal: NTs = NE and ACh, but inhibition or excitement as a result is tissue type dependent.
- Non-neuronal: chemical factors include metabolic products, ions, gases and hormones (endothelin, angiotensin, vasopressin) and regulate SM via electro-mechanical stimulation/inhibition and/or pharmacomechanical stimulation/inhibition
8
Q
Difference between electromechanical coupling and pharmacomechanical coupling
A
- ) Electromechanical coupling refers to a change in membrane permeability that results in depolarization (stimulation of SM) or hyperpolarization (inhibition of SM)
- ) Pharmacomechanical coupling refers to stimulation/inhibition of SM contraction by signaling molecules
9
Q
Explain how electromechanical stimulation and inhibition can occur
A
- Stimulation: if membrane sodium or calcium channels were opened resulting in depolarization and SM contraction
- Inhibition: if membrane sodium or calcium channels were closed or if potassium channels were opened resulting in hyperpolarization and inhibition of SM contraction
10
Q
Explain how pharmacomechanical stimulation and inhibition can occur
A
- ) stimulation: some hormones activate PLC pathway through their receptor, this increases intracellular concentrations of IP3 resulting in SM contraction
- ) inhibition: some hormones will activate PKA pathway leading to phosphorylation of MLCK, which prevents calmodulin-CA complex from activating MLCK and inhibiting the contraction process. Also, pathways that activate myosin phosphatase can lead to inhibition of the contraction process.
11
Q
Describe how calcium participates in both smooth muscle mechanical and electrical events
A
- Smooth muscle APs are the result of movement of depolarization through Ca and Na into the cell from the EC environment
- Calcium once inside the cell also participates in binding to calmodulin and therefore activation of MLCK, which regulates the contractile process
12
Q
True/False. The primary source of calcium is the SR in smooth muscle.
A
- False, the primary source is from the EC fluid. SR is not as well developed as seen in SkM and is a “weak” source of calcium
13
Q
Effect of NE and ACh in gut to lumen and sphincter
A
- ) Lumen: SNS releases NE that results in decreased peristalsis and tone, PSNS releases ACh that increases peristalsis and tone
- ) Sphincter: SNS release NE that results in increased sphincter tone, PSNS releases ACh that results in relaxation of the sphincter’s tone
14
Q
Diagram the types of smooth muscle action potentials (spike potentials and APs with plateaus) as well as the resting slow wave. Know how calcium, sodium and potassium participate in the APs
A
- Two types of APs: spike potentials and APs with plateaus
- Spoke potentials result from movement of Ca (causes AP) and Na (for upstroke) into the cell causing depolarization and repolarization resulting from movement of K out of the cell
- APs with plateau: plateau d/t prolonged and slow opening of Ca channels with repolarization mediated by K
15
Q
What are slow wave potentials?
A
- Series of continuous depolarizations (not to threshold therefore not AP) and repolarizations that serve as pacemakers for some types of smooth muscle such as that in the GI. Thought to be the result of sodium pumping or rhythmic changes in ion conductance
- APs only occur at peak of slow wave with stimulus
