Vascular Smooth Muscle Flashcards
What are the properties of the tunica intima? What is its function?
is the innermost layer of blood vessels
is the thinnest layer
- formed of a thin layer of endothelial cells
lines the lumen
- has tight junctions to prevent leakage
secretes many vasoactive substances
What are the properties of the tunica media? What is its function?
is the second layer of blood vessels
- is made of circular and spiral layers of smooth muscle which contain collagen and elastin
= provide structural support
sympathetic innervation can occur
= contains nerves
surrounded by internal elastic lamina and external elastic lamina
- separates the tunica intima and media
- anchors the vessels with surrounding tissues
What are the properties of the tunica adventitia? What is its function?
is the outermost layer of blood vessels
- is predominately made of connective tissue which contain collagen and elastin
= collagen and elastin are produced by fibroblasts and provide strength/structural support
contain
- nerves = can be innervated by the CNS
- adipocytes
- fibroblasts
contain vaso vasorum in large vessels
- is an independent vascular system
= are small blood vessels that supply nutrients to large vessels
How do actin and myosin work in the VSMC?
actin and myosin are arranged in bundles (are longer than CM filaments)
- actin is anchored to dense bodies in the cell
= linkage prevents sarcomere movement in the cell
- dense bodies are linked to the cytoskeleton
- integrins anchor the cytoskeleton to the inner cell wall
- upon contraction, the sarcomere shortens thereby pulling the intermediate filaments and shrinking the cell
How are VSMCs different to CMs?
VSMC
- are spindle shaped and are shorter in length
- have a single central nucleus (CM is binucleated)
- have no striations = due to the disorganisation of contractile cells
- has a lower proportion of sarcoplasmic reticulum
- major source of calcium is the extra cellular fluid
= makes the cell sensitive to many substances - caveolae (folds in the VSMC) increase surface area:volume
- gap junctions allows the spread of electrical excitation to spread between neighbouring cells
- innervation of tunica media and adventitia
= both contain nerves
= nerve terminals contain varicosities - vesicles containing neurotransmittters
How is EC- coupling in VSMCs different to CMs?
VSMC
- does not rely on calcium and troponin C interaction
= myosin phosphorylation triggers contraction which is controlled by intracellular calcium levels (influenced by extracellular calcium and the SR)
- has slower contractions
= uses less ATP and has a slower rate of cross bridge cycling
What is the mechanism for contraction in the VSMC?
calcium binds to its four binding sites on calmodulin (protein)
calcium/calmodulin complex binds to and activates the myosin light chain kinase (MLCK)
- MLCK is typically inactive due to autoinhibition
MLCK phosphorylates the light chain of the myosin head
- transfers a phosphate using ATP
myosin forms a cross bridge with actin
myosin head cycling pulls/slides the myosin/actin fibres past each other
- muscle shortens/contracts
What is the basal tone of VSMCs? What causes it? What is its purpose?
VSMCs are always in latch state
- caused by actin-myosin attachment without consuming ATP
= means contraction is not dependent on ATP
= ATP is required to release the cross bridge
- results in basal tone
= permanent level of partial contraction which allows vasoconstriction or vasodilation (can be relaxed due to already being in a contracted state
How can contraction be stimulated?
circulating hormones - adrenaline
neurotransmitters - NA, ATP, neuropeptide Y
What are the two phases of contraction in VSMC?
electromechanical coupling
pharmacomechanical coupling
How does electromechanical coupling occur in VSMCs?
NA released by sympathetic innervation binds to GqPCR
casings its activation
Gq (GqPCR) is coupled to phospholipase C (enzyme) causing its activation
PLC metabolises phosphotidylinositol 4,5 bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG)
IP3
- binds to IP3 receptors on the SR causing intracellular calcium release and a rise in cystolic calcium levels
- calcium binds to a chloride channel activating outward chloride ion current
- depolarisation occurs as the membrane potential becomes more positive
= slow depolarisation
DAG
- activates non-selective cation channels
- mediates the inward movement of sodium and calcium ions
- depolarisation occurs
depolarisation activates calcium channels
- voltage gated calcium channels (LTCCs) activation causes further depolarisation
calcium activates MLCK
How does pharamcomechanical coupling occur in VSMCs?
some receptor do not alter membrane potential
NA binds to an alpha adrenoceptor which is a GqPCR
Gq is coupled to phospholipase C (enzyme) causing its activation
PLC metabolises phosphotidylinositol 4,5 bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG)
IP3 binds to IP3 receptors on the SR causing intracellular calcium release and a rise in cystolic calcium
calcium influx from receptor operated non-selective cation channels (ROCs)
- influx of calcium from the ECF
- increased cystolic calcium levels
- MLCK activation
occurs in large arteries that do not give action potentials
What is the function of MLCP? How does it act during contraction?
during contraction, MLCP is mediated by rhoA (rho associated kinase)
- rhoA inhibits MLCP during contraction
= are G12PCR
rhoA is activated by sustained calcium release
- rhoA maintain contraction which calcium level decreases
this is important as myosin light chain phosphatase typically inhibits myosin light chain causing relaxation
How are the adrenoceptors in VSMC different? alpha-1 alpha-2 beta-1 beta-2
alpha-1
- are in systemic blood vessels
- respond more to NA than A
- can be GqPCR or G12PCR
alpha-2
- are in cutaneous blood vessels
- respond more to A than NA
- are GiPCR
beta-1
- are in cardiac cells
beta-2
- are in arteries of myocardium, skeletal muscle and liver
- respond more to A than NA
- are GsPCR
How does relaxation occur in VSMCs?
beta-2 adrenoceptor stimulation by adrenaline
stimulation of GsPCR
- activates adenylyl cyclase
- generation of cyclic AMP
- protein kinase A activation
= sarcolemmal calcium ATPase activation - efflux of calcium to the ECF
= potassium channel phosphorylation - potassium ion efflux causing hyperpolarsation and reduces the possibility of LTCCs opening
= MLCK inhibition results in the contractile apparatus (actin/myosin) having decreased sensitivity to calcium
