Lecture 10 Vascular Smooth Muscle

Question 1

Describe the different components of vascular smooth muscle

Answer 1

myosin - low ATP breakdown ability, site of contractile regulation
actin - no nebulin, troponin, inhibited by calponin and caldesmon
dense bodies - where sarcomeres aim at
gap junctions - form functional syncytium, allow of electrical coupling
macula adherens (dense plaques) - physical coupling
caveolae - lipid rafts with high concentration of ion channels

Question 2

Describe the excitation-contraction coupling

Answer 2

Ca2+ binds to calmodulin, this complex then activates MLCK, which phosphorylates the two regulatory light chains on myosin. This allows myosin to breakdown ATP. MLCP dephosphorylates the light chains, but is inhibited by RhoA (calcium sensitization)

Question 3

Describe the latch phenomenon

Answer 3

When there is sustained stimulation, the Ca2+ has a spike and then plateaus, but still manages to maintain a high level of force production and sustained tenstion. This is because MLCP dephosphorylates a portion of myosin, which has a lower rate of detachment from actin, this slow cross-bridge detachment maintains tension

Question 4

Describe force and velocity in smooth muscle

Answer 4

Can maintain the same max force as striated muscle, but has lower Vmax. As more myosin gets phosphorylated, the velocity of shortening increases and max force increases

Question 5

Describe the transporters involved in Ca2+ regulation (both for release and clearance of Ca2+)

Answer 5

Release:
SOC = store operated channels. Sense decrease in concentration of SR calcium, Ca entry from extracellular
ROC = receptor operated channels. Activated by second messenger systems (e.g. DAG) and is a non-selective cation channel. It then depolarizes CaV1.2, allows Ca2+ in from the outside
Istretch = K+ or non-selective cation channel, sense stretch, and depolarizes CaV1.2
IP3, RYR3 - release Ca from SR, RYR is CICR (mainly IP3 though)

Clearance:
NCX = 3 sodium in, 1 Ca out, low affinity, high capacity
PMCA = high affinity, low capacity
SERCA = high affinity, low capacity

Question 6

Describe the pathway of IP3 release

Answer 6

NE on alpha1, activates Gq, activates PLC. Cleaves PIP2 into IP3 and DAG. IP3 causes Ca release from SR. DAG activates PKC, causes Ca sensitization by inhibiting MLCP, leads to increased crossbridge formation

Question 7

Compare skeletal muscle, cardiac muscle, and smooth muscle contraction

Answer 7

Skeletal muscle: CaV1.2 physically coupled to RYR, therefore depolarization necessary, but very little Ca2+ entry
Cardiac muscle: CICR, CaV1.2 very close in proximity to RYR. therefore Ca2+ entry is necessary
Smooth muscle: IP3 dependent release