Intro to Smooth Muscle Flashcards
Peripheral Resistance equation
(8 x μ* x Length )÷ r^4
*viscosity
Contraction of VSMCs
- Pull inwards to shorten around the vessel they surround
- As they shorten, the get thicker (conserving their volume) and pucker out in places
- Can easily shorten to 50% their length
Morphology, Arrangement of VSMCs
- Thin, spindle-shaped cells
- Arranged side by side
- May wrap around the vessel many times in smallest
arterioles
Structure of VSMCs
- Contractile apparatus is connected to the membrane to ensure contraction is translated
- Actin filaments are attached to membrane associated desmosomal bodies (DB) and dense bodies (= to z-lines)
- Caveoli invaginations to aid in EC coupling
The SR 1
- Small (1-7.5% of cell volume)
- Poorly coupled to outer plasma membrane
- Contains Ca, buffered by calreticulin and calsequestrin
SR channels/receptors and regulation of SR Ca Uptake
Ca Uptake
- SERCA2b/3
reg by PL*
inhb by thapsigargin/cyclopiazonic acid
Ca release
- IP3R
- RyR
(PL reg by cA/GMPK)
The SR Ca release channels
RyR
- CAICAR?
- Not much known
- May contribute to same process as IP3R
IP3R
- Ligand activated
- Sparks
- Ca waves propagate through cells
- Ion channel and TF regulation
VSMC Structure 2 (‘cytoskeletal’ connection)
- Quasi-myofibrils run longitudinally
- Intermediate filaments run laterally, connecting the dense bodies to one another
Force Production in VSMCs compared to CMs (LTR and CBC)
Length-Tension R
- Can exert force over a wide range of length
- Can shorten far more than CMs (50% vs 15%)
Cross-bridge Cycle
- Cycle of motor is the same as in CMs
- Release of Pi/ADP (rate-limiting) is much slower
- Force-generating fraction of the cycle is ~30%, only 5% in cardiac muscle
EC Coupling in VSMCs
-Cells must maintain steady tension at precise level, have varying dependence on these two systems
Electromechanical
Pharmacomechanical
- Vasoconstrictor agonist to GPCR has two actions:
1. Open Ca channels
2. Activate phospholipase C, IP3 from PIP2, IP3 on IP3R to cause CAICAR
VSMC vs CM Structure,
Appearance
- Both have elements running along (z-lines or dense bodies)
Appearance
- No physically defined sarcomere in VSMC
- VSMC smaller and thinner
Myosin
- VSMC myosin more similar to that of non-muscle motile system myosin than CM myosin
Side-polar myosin
- My. tails in anti-parallel arrangement
- Bars of cross-bridges in opposite direction on each side
- Dense bodies (with actin) interdigitate on both sides
Role/Expression of SMCs in vasculature
- Varies TPR by altering radius
- Maintains vascular tone
- Maintains circumference in high pulse-pressure arteries
- Most in arterioles and muscular arteries, some in aorta
- Veins/venules have less but can alter diameter greatly due to the low pressure in the venous system
Ca Regulation of Contraction
Primary Pathway:
Ca binds calmodulin -> activates MLCK* -> activates myosin
Secondary Pathway:
Ca binds CaBP -> CaBP relieves caldesmon inhibition of myosin
*also activated by MAPK
