Smooth Muscle Flashcards
Where does one find smooth muscle and what is its function?
- Surrounds hollow organs and blood vessels
- contraction/repulsion and vascular resistance
Innervation of smooth muscle
-autonomic
Nucleus of smooth muscle
mono nucleated: can reenter cell cycle and proliferate unlike skeletal and cardiac
Electrical description of smooth muscle cells
-can either be isolated (like skeletal muscle) or connected to neighboring cells (cardiac)
Unlike skeletal muscles, smooth muscles usually are slower and involve continuously ongoing ______ contraction/force
tonic
________ are not readily observed in smooth muscle
- striations
- actin and myosin are not organized into sarcomeres in smooth muscle
Tropomyosin is present in smooth muscle in about the same ration to actin content as in skeletal muscle, and is similarly associated with actin filaments. One major difference in protein content is the complete absence of _______
-troponin complex (I,C, and T) which confer Ca2+ sensitivity upon the skeletal and cardiac muscle contractile systems
Instead of troponin proteins, smooth muscle cells are seen to contain either ______ or ________. The function of these isn’t exactly known, but they likely play modulatory functions in fine tuning the smooth muscle contractile characteristics.
- Caldesmon
- Calponin
Compare amounts of actin in smooth muscle to actin in skeletal muscle
-twice as plentiful in smooth
Several actin filaments in smooth muscle may pass through or terminate in a protein-rich _________ or __________ which acts as a point of thin filament anchorage for the transmission of generated force.
- Dense bodies
- Desmesomes
Some dense bodies appear bound to the plasma membrane and others suspended in cytoplasm. In order to support these cytoplasmic anchorage points, a network of _________ made up of _______ interconnects membrane and cytoplasmic dense bodies.
- Intermediate filaments
- Desmin/Vimentin/both
In addition to desmin, the proteins ________ and _______ have been identified in both skeletel muscle Z banks and muscle muscle dense bodies.
- Alpha-actinin
- Tropomyosin
The role of desmin filaments in skeletal muscle cell however is to maintain lateral registration of myofibrillar Z bands. These similarities in protein content and function support the notion that the intermediate filament lattice/dense body network is essentially _________.
A dispersed Z band or more appropriately, that Z bands arose as an aggregate of dense bodies
Smooth muscles may have less myosin than striated muscle, but it can generate larger forces still because?
-The myosin is longer (and more actin)
Smooth muscle myosin must be activated (turned on) to be functional. How is this accomplished?
-Phosphorylation of myosin light chain (MLC)
If troponin is missing in smooth muscles, how does Ca2+ activate contraction?
- Calcium enters cells and binds to calmodulin
- Calmodulin can now bind and activate MLCK
- MLCK will phosphorylated MLC and turn on myosin
Dense bodies are composed of mainly __________, the major protein of the Z-line, and act to anchor the thin filaments, much like the Z line in striated muscle
-Alpha actinin
Intermediate filaments, _________ and ________, attach intracellular dense bodies to the membrane dense bodies
-Desmin and vimentin
The forces generated by actin and myosin interaction are transmitted to the cell membrane, and the contractile apparatus of adjacent cells are linked between membrane attachment-plaques, or desmesome-like attachments to do what?
-Transmit force of contraction across cells
Because of structure of smooth muscle, individual cells have can shorten by _____________.
-Over 70% of their resting length
Thick/thin filament interaction in smooth muscle can be termed _________, as the individual thin filaments are not bound by a sarcomere to only associated with a single thick filament.
- Plastic
- Plasticity has important implications for force-length relationships
4 types of junctions between smooth muscle cells
- Simple opposition and Intermediate contact (no electrical or mechanical connectivity)
- Desmesome (mechanical, no electrical connectivity)
- Gap junction (electrical connectivity)
Smooth muscle is regulated by _______, but does not contain the protein ______.
Calcium
Troponin
__________ phosphorylates MLC and _________ dephosphorylates/deactivates MLC
- MLCK
- MLC phosphatase
- By regulating the activity of these 2 enxymes, smooth muscle is able to increase and decrease the p-lation of MLC and thus either contract or relax
At low Ca2+, MLCK is ________. What happens as calcium increases?
- Inactive
- Increase calcium, increase calmodulin bound to calcium ( homologous to troponin C)
- After binding 4 calcium molecules to calmodulin, it binds to and turns on MLCK
2 sources of calcium for smooth muscle contraction
- Electromechanical coupling
2. Pharmacological coupling (depolarization independent)
Electromechanical coupling
-Smooth muscle contracts in response to rise in intracellular Ca2+
This can be derived through L-type Ca2+ channels or other receptors
Pharmacomechanical coupling
- Smooth muscle can contract without a change in Vm
- Cell membrane has many GPCRs that activate phospholipase C, hydrolyze PIP2 into IP3 and DAG
- IP3 receptor on SR and high sequence homology to RyR in cardiac muscle
- Increase in Ca2_ induced by binding of an agonist to its receptor without a change in Vm is called pharmacomechanical coupling
Does smooth muscle have T-tubules?
-No
Smooth muscle forces varies with ____________.
- MLC phosphorylation
- force shows a linear increase with MLC phosphorylation until approximately 60% of MLC is phosphorylated, after which force is constant (isometric)
The linear relationship between Ca and phosphorylation and force holds for contractions triggered by depolarization. However, for agonist stimulation, what occurs? What is this phenomenon called?
- at any particular [Ca2+], force is higher than for a contraction stimulated by depolarization
- This phenomenon is called agonist-induced calcium sensitization of the contractile filaments
What is the mechanism for this extra force in agonist depolarization?
- Appears to be a G-protein coupled regulation of MLC phosphatase
- With agonist activation, MLC phosphatase activity is decreased, and at any Ca2+ concentration, MLC phosphorylation is increased and more force is generated
2 sources to regulate smooth muscle contraction
- Increase MLCK activity: increasing calcium activated MLCK which phosphorylates RLC
- Inhibit MLC phosphatase: this is the mechanism agonist activation relies on
2 pathways by which agonists increase contraction through inhibiting MLC phosphatase
- G-protein activation of rho, leads to activation of rho kinase, that p-lates the MBS of MLC phosphatate causing inactivation
- PKC inactivates MLC phosphatase via CPI-17
Mechanism of agonist activation of smooth muscle relies on _________.
Inhibition of MLC phosphatase
Similar to cardiac muscle, there is no _________ for smooth muscle.
-Antagonist
Relaxation of smooth muscle requires dephosphorylation of the MLC. How can this be achieved?
-Increase in activity of MLC phosphatase or decreased activity of MLCK
3 ways to relax smooth muscle (looking for mechanisms)
- Decreasing calcium leads to less MLCK activation and MLC phosphatase dephosphorylates RLC (pumps in SR and PM to do this)
- Subset of smooth muscle: NO (EDRF) increases cGMP, which activated PKG, which binds and activates MLC phosphatase; important in vasculature
- B-receptor stimulation: increased cAMP leads to phosphorylation of MLCK, which decreases MLCK activity; also occurs in vasculature
Intermediate filaments, similar to compresses spring, generate forces opposing shortening and _________ the smooth muscle cells to their original length
-Re-lengthen
Mechanism of viagra
-Inhibits the phosphodiesterase that hydrolyzes cGMP and increases the relative concentration.
Mechanism of relaxation of smooth muscle by activating MLC phosphatase is termed ________.
Calcium desensitization
cAMP target in smooth muscle
- Converts MLCK to an inactive pool that cannot be activated by Ca2+-CaM
- Phosphodiesterase inhibitors can lead to increased relaxations because cAMP will last longer
In patients with COPD, why is it beneficial to use selective B1 (cardiac -specific) Beta blockers to lower heart rate?
-If used non selective beta blocker, the effect in airway smooth muscle would be to cause constriction which exacerbate symptoms of COPD
in addition to affecting the heart rate
Electromechanical coupling involves__________ and pharmacological coupling involves _________.
- Entry of calcium via v-gated calcium ion channels (L-type)
- Receptor operated Ca2+ channels and SR Calcium release via GPCR and IP3
Smooth muscle has a unique property of being __________.
resistant to fatigue
Smooth muscle force maintenance
-Force persists despite calcium levels and MLCK levels falling
During force maintenance, rate of ATP hydrolysis falls to low levels
Phasic contraction vs. Tonic contraction
Phasic is in smooth muscle of GI and fires AP. twitch-like response
Tonic: vasculature, doesnt fire AP so need to hold stimulation. But in order to hold isometric force, cross bridges slow down and less ATP is used
Slow ATPase cycling allows vasculature to hold force with ______.
Little ATP expenditure
True or False: Due to smooth muscles lacking sarcomeres, they do not have optimal length-tension curves
-False
Force vs Velocity relationship of Smooth muscle
- hyperbolic shape
- like cardiac muscle, Vmax is dependent on level of activation. Both cardiac and smooth muscle have internal load that is responsible for relengthening of the tissue after contraction. Because of this internal load, when both cardiac and smooth muscle contract, the force that the muscle must generate must be greater than the internal load for shortening to occur
-As the level of activation (MLC P-lation) increases, the velocity at any after load increases
What type of smooth muscle cells are single unit vs. multi-unit neuronally regulated?
-Single unit: GI tract, bladder, uterine. electrically coupled to contract as single unit
Multi-unit: vascular, similar to skeletal muscle
Tonic vs Phasic functional classification examples of smooth muscle
Tonic: arterial; resting tone and slow contraction, slowing cycling Myosin isoform
Phasic: GI tract; more rapid contraction and relaxation; fire APs and faster myosin isoform
For a multi-unit smooth muscle, each smooth muscle cell is ________.
Independent
Single nerve fiber will innervate several smooth muscle cells and and individual smooth muscle cell may have input from more than a single nerve
For tonic smooth muscle, in absence of extracellular Ca2+, contraction occurs which suggests what?
- Major source for Ca2+ of contraction is internal SR stores
- This type of smooth muscle maintains a continuous resting tone, and is thus referred to as tonic smooth muscle
Primary source of calcium for single unit smooth muscle:
-transmembrane Ca2+ flux during AP
Tonic smooth muscle velocities
- Force activation, force relaxation, actomyosin ATPase activity and maximum velocity of muscle shortening are all slow
- All rapid in phasic muscle
