Vasuclar Smooth Muscle Flashcards
How are arterioles organized, explain their role in resistance
Organized in series
- in general have small radius so resistance is high
- site of resistance regulation- a change in its radius has large effects on R
capillaries have highest R but are in parallel so R isn’t variable
Composition of blood vessels: Aorta
High elastic fibers- allow high compliance
Highest internal radius
Composition of blood vessels: Arterioles
Larger wall thickness than internal radius
High smooth muscle b/c controls constriction of radius
Composition of blood vessels: Cappillaries
Smallest vessels
Only endothelial cell layer
Width of lumen of arteriole
10-30 micro m
What does VSM stand for
Vascular smooth muscle
What are the terms for constriction and dilation in smooth muscle
Vasoconstriction and vasodilation
What regulates smooth muscle contraction
Thick filament
What does SMC stand for
Smooth muscle cells
What is in the VSM thin filament
- Actin
- Calponin
- Caldesmon
* no nebulin, Tn complex*
What does calponin do
Inhibits actin- myosin interactions
What does caldesmon do
Inhibit actin-myosin interactions
What is the pattern and shape of vascular smooth muscle
Irregular pattern- no striations no Z lines
Spindle shaped
How do the thin filaments anchor
Dense bodies
- no Z lines in smooth muscle
How do gap junctions differ in different smooth muscle. Provide examples
Not all smooth muscle are connected for functional syncytium, but some are
ex. Aorta- multi unit, not coupled
ex. Arterioles- single unit, coupled
What creates mechanical coupling between smooth muscle cells
Adherens junctions (dense plaques)
What are the invaginations in smooth muscle called
Caveoli
lack t-tubules
How does the amount of mitochondria differ in smooth muscle vs cardiac muscle
Few mitochondria in vascular smooth muscle vs cardiac muscle
What cells can proliferate
Smooth muscle cells can proliferate (angiogenesis)
Striated muscle can not proliferate
What is the role of the myoendothelial junction
Allows communication between endothelium and smooth muscle in arteries
Where is smooth muscle located in relation to cardiac muscle
Smooth muscle is deep to cardiac muscle
Compare structures in vascular smooth muscle vs cardiac muscle
In smooth muscle:
1. SR less regular
2. Caveoli instead of t-tubules
3. Fewer mitochondria
How does the # of mitochondria differ in VSM vs cardiac and why
Fewer mitochondria in smooth muscle b/c glycolysis can support non-contractile ATP needs
What are caveoli and what is their function
-Caveoli are specialized lipid rafts, invaginations of the cell membrane
-contain Ca channels and ion channels
-can localize signaling molecules
Explain the initiation of cross-bridge cycling in smooth muscle
-Calcium binds to calmodulin (Ca-CaM) activating it
-active calmodulin binds to myosin light chain kinase (MLCK)
-active calmodulin/MLCK complex phosphorylates regulatory myosin light chain (MLC) using the hydrolysis of ATP
-activated myosin can now form a cross bridge (semi-permanent phosphorylation)
What triggers contraction in smooth muscle, how does this differ in striated muscle
Ca2+ triggers contraction in VSM
- directly activates contraction via MLCK
In striated muscle Ca2+ acts as a disinhibitor
What enables cross bridge cycling
Myosin light chain phosphorylation enables xb
(Thick filament regulated)
What stops force generation in VSM
Relaxation requires myosin light chain phosphatase (MLCP)
- force is sustained (system active), even when Ca2+ levels drop, as along as MLC is phosphorylated
What does RhoA do
RhoA inhibits MLCP (myosin light chain phosphatase) which allows contraction to continue because regulatory MLC remains phosphorylated
What causes smooth muscle relaxation
-Requires MLC phosphatase (MLCP) and decrease in calcium concentration
-dephosphorylate regulatory MLC which prevents new cross bridge formation
What is the latch state
Slow cross-bridge detachment maintains tension with lower ATP use
- dephosphorylating myosin has a slow rate of detachment from actin
- decrease in Ca, low level of MLCK activation, but enough to sustain tension (no new force generation)
How does the length tension relationship differ in VSM vs cardiac
Length tension relationship is more broad in smooth muscle (because side polar myosin?)
Smooth muscle force-velocity curve
- slow velocity of shortening
- high force generation
What allows smooth muscle to have a large length range
Side polar myosin thick filaments
-easier to form cross bridges and pull actin
- myosin on angle
How can shortening velocity be increased in smooth muscle
Increased with more phosphorylated MLC
- inc Ca, activate MLCK, phosphorylate regulatory MLC: pathway causes increase in shorting velocity also increases maximum force
Name the channels involved in Ca regulation in smooth muscle
SOC: store-operated channels
ROC: receptor-operated channels
Istretch channels
IP3 mediated Ca release from SR
NCX channel (Ca out Na in)
PMCA (Ca out with ATP use)
SERCA2b (2Ca into SR)
Store Operated Channels
- types, activation, role
- Channels: Orai, TRPC1, TRPC3
- activated by decrease in calcium concentration in SR. SR Ca sensor- STIM (protein)
- calcium sent directly into SR
Receptor-Operated Channels
- types, activation, role
- channels: TRPC, TRPV, TRPM
- 2nd messenger activated
- non selective ion channel lets in other ions than Ca. Causes depolarization which opens Cav1.2 channels
Istretch channel
- types, role
- K+ channels or non-selective cation channel
- depolarization causes Cav1.2 opening
Ca release from SR
-activation, role
Two ways of Ca release from SR:
RyR3- Ca activated
IP3R- IP3 activated
- SR Ca release contributes to transient Ca peak in cell
Which channels contributed to Ca concentration in cell vs time graph and where is their contribution
Transient Ca2+ peak- SR Ca2+ release
Sustained Ca2+ plateau- Ca2+ entry from ROC, SOC, Cav1.2, Istretch
Clearance of cytosolic Ca2+- NCX, PMCA, SERCA2B
List the affinity and capacity of the Ca clearance channels
NCX: low affinity, high capacity
PMCA: high affinity, low capacity
SERCA2B: high affinity, low capacity
(affinity- binding for transport, capacity- amount moved)
What is the main contributor for Ca regulation in vascular smooth muscle
SR Ca release is the main driver of increased Ca. IP3 mediated Ca release
Pathway for producing IP3
Noradrenaline binds to alpha1 receptors. This causes the release of the Gq G-protein on the receptor which activates PLC- phospholipase C. PLC converts phosphatidylinositol biphosphate- PIP2 into IP3- inositol triphosphate and DAG- diacylglycerol.
Pathway of IP3 causing increased force of contraction
IP3- inositol triphosphate will bind to IP3 receptors on the SR and allow Ca release from the SR through these channels. This will increase the Ca levels in the cell, therefore increasing cross bridge formation and increasing the force of contraction
How does DAG increase the force of contraction of vascular smooth muscle
DAG- diacylglycerol activated PKC- protein kinase C which inhibits MLCP- myosin light chain phosphatase. This causes an increase in Ca sensitivity of VSM contraction therefore increasing the cross bridge formation and increasing the force of contraction
How is Ca released and taken up in the SR- sarcoplasmic reticulum
Released: RyR and IP3 channels
Uptake: SERCA2B which is PLB- phospholamban regulated
The Sarcolemma channels involved in Ca regulation
Ca entry: Cav1.2 (voltage gated), ROC (receptor operated), SOC (store operated), Istretch (stretch-activated cation channel)
Ca exit: NCX (Na Ca exchanger), PMCA (plasma membrane Ca ATPase)
