VASCULAR: VASCULAR SMOOTH MUSCLE Flashcards
2 reasons why arterioles are important
Resistance is high due to small radius
Site of regulation of resistance; change radius has large effect on resistance- Arterioles are a major determinant of flow
Blood can be ____ between organs according to demand by regulating the radius of the arterioles.
shunted
Why aren’t capillaries a major determinant of flow like arterioles are?
Capillaries offer the highest resistance but they are not in parallel and their resistance is not variable.
What is the width of the arteriole?
10-30 um
vasoconstriction
contraction of smooth muscle (since they are concentric rings)
vasodilation
relaxation of smooth muscle
The number of smooth muscle cell layers is proportional to ________
wall thickness
Describe the contractile elements of vascular smooth muscle
- Thick filament: made up by myosin
- Low ability to breakdown ATP
- Site of contractile regulation - Thin filament: made up by actin; anchor into dense bodies
- No nebulin, TnI, TnC, or TnT
- Calponin and caldesmon: inhibit actin-myosin interactions
- Thin filaments anchor into dense bodies - Gap junctions: structures that create functional syncytium;
- Not all smooth muscle cells are connected- Multi unit (not coupled) ex: aorta
- Single unit (coupled) ex: arterioles
- Adherens junctions (aka dense plaques): mechanical coupling between smooth muscle cells; dense plaque
How are VSM oraganelles arranged differently from the heart muscles?
- Sarcoplasmic reticulum are less regular
- Some associates with PM
- Some extends toward myofilaments
- Caveoli instead of T-tubules:
- Specialized lipid rafts
- Contain Ca2+ channels and other ion channels
- Can localize signaling molecules
- Fewer mitochondria:
- glycolysis can support noncontractile ATP needs
- myoendothelial junction: extra connection
Vascular smooth muscle compared to regular muscle
- In smooth muscle, myosin is the site of contractile regulation
- In other muscle it is actin
- No nebulin, Tni, TnC, or Tnt in VSM
- Instead, calponin and caldesmon inhibit actin-myosin interactions
- VSM has no striations but instead an irregular pattern - VSM have far less organization
- few mitochondria vs cardiac muscle
- lack t-tubules (caveoli instead)
- Smooth muscle cells can proliferate unlike striated muscle; this is the basis for angiogenesis
What is the trigger for contraction in vascular smooth muscle?
- Ca2+
How does vascular smooth muscle contraction begin?
- In smooth muscle Ca2+ directly activates contraction via MLCK
- Calmodulin: binds to calcium and becomes Ca-CaM; cytosolic protein just floating around; not bound to actin
- Ca-CaM targets MLCK (myosin light chain kinase) binding together to become calmodulin/MLCK complex
- MLCK phosphorylates myosin light chain head to activate myosin to begin contraction
How does relaxation occur for vascular smooth muscles?
- requires myosin light chain phosphatase (MLCP)
Describe the latch state of VSM contraction
It’s due to sustained stimulation (tonic stimulation)
- Sustained stimulation maintains modest ↑ Ca2+, required for sustained tension
- Rise in Ca2+ results in low level of MLCK activation
- MLCP dephosphorylates a portion of myosin molecules
- Dephosphorylated myosin has a ↓ rate of detachment from actin
- Phosphatase is slow to release and as soon as they deactivate, they can be reactivated again!
- Slow cross-bridge detachment maintains tension with lower ATP use
Describe the force velocity relationship in smooth muscle
- Development of force is slow as it doesn’t need to be fast. A slow sustained contraction is needed.
- Slow velocity of shortening
- High force generation
- Large range of length due to side polar myosin thick filaments
What transported are involved in Ca2+ regulation out of the SR of the VSM?
RyR3 – Ca2+ activated
IP3R – IP3 activated
What are ROCs?
Receptor operated channels
Example: certain TRPCs, TRPVs, TRPMs
Activated by second messengers
often non-selective cation channels → lead to depolarization and open Cav1.2 (allow for sodium entry)
What are SOCs?
Store operated channels
SOCs sit in the membrane and has a Ca2+ sensor called STIM.
Channel examples = Orai, TRPC1, TRPC3
Activated by decrease in Ca2+ in SR
What are Istretch channels?
K+ channels or non-selective cation channel → depolarization, Cav1.2 opening
What transporters move calcium out of the VSM cells?
NCX: still here trading 3 Na+ in and 1 Ca+ out
PMCA: plasma membrane calcium ATPase; uses ATP to move calcium out of the cell
Describe SERCA in VSM
slower than in cardiac muscle.
What is the main driver of increased Ca2+ after G-protein coupled receptor activation?
Ca2+ release from the SR
Where does the IP3 come from?
Agonist like norepinephrine → acts on ɑ1 which is coupled to Gq→ Gq actives PLC (phospholipase C) → PIP2 (phosphatidylinositol biphosphate) → IP3 + DAG → →
→ IP3 (inositol triphosphate) increases sarcoplasmic Ca2+ release by acting on IP3 channel
→activates PKC (protein kinase C) → MLCP → increases Ca2+ sensitivity of VSM contraction
Compare excitation coupling in skeletal muscle, cardiac muscle, and smooth muscle
Skeletal muscle
- voltage dependent Ca release (VDCR)
physical coupling of Ca channel and RyR
- depolarization required for RyR Ca2+ release
- but Ca2+ entry not necessary
Cardiac muscle – Ca induced Ca release (CICR)
- Ca2+ entry through Cav1.2 is an absolute requirement
- Cav1.2 in close proximity with RyR
- triggers RyR Ca2+ release from SR
Smooth muscle - IP3-induced Ca release (IP3 ICR)
- Cav1.2 and RyR not in close opposition (little CICR)
- binding of IP3 to SR IP3 receptor triggers Ca release
- RyR causing some CICR
- role for Ca2+ entry pathways across sarcolemma
