L4 Smooth Muscle Physiology Flashcards
Smooth Muscle & Calcium
Sources of Ca in smooth muscle contraction:
IP3 gated Ca channels in the SR
Voltage gated Ca channels in membrane
Ligand gated Ca channels in membrane (NT or hormone opens channel)
Smooth muscle myosin-linked E-C Coupling
AP in smooth muscle membrane opens voltage-sensitive Ca channels.
Intracellular Ca goes up
Ca binds to Calmodulin
Ca/Calmodulin activates Myosin-light-chain Kinase (MLCK)
MLCK P’s myosin and makes it active
(Myosin-light-chain Phosphotases de-activate the myosins and cause relaxation
Smooth muscle contraction modulators:
cAMP and PKA P the MLCK so that it’s inactive, this not allowing it to activated the myosin – OFF
cGMP stimulates the MLC Phosphotase thus turning contraction OFF
Single Unit
multiple cells acting as one
Cardio
Multi Unit
individual cells act alone
skeletal
ANS stimulation of smooth muscle
Alpha 1 -adrenergic = smooth muscle activation because it uses Gq protein couple receptors which activates PLC. PLC cleaves PIP2 into IP3; IP3 causes Ca outflow from the SR, and therefore contraction.
Beta 2 - adrenergic = smooth muscle relaxation; inhibits L-type Ca channel flow
Beta 2 uses Gs protein coupled receptor which turns on adenylyl cyclase to make cAMP from ATP. cAMP P’s MLCK which turns OFF the myosin and turns OFF contraction
How does NO cause smooth muscle relaxation?
NO activates guanylyl cyclase, which makes cGMP. cGMP:
1) inhibits Ca entry into cell
2) activates K+ channels to hyperpolarize
3) activates the MLC phosphatase which makes myosin inactive
These all inhibit contraction and enhance relaxation
Parasympathetic nerve activity & endothelial/smooth muscle interaction
varicosities of nerves/blood vessels release a NT or hormone which either diffuses or has a receptor on the cell. Appropriate effect takes place.
If multi unit, each smooth muscle cell is innervated separately. If single unit, things propagate through the connections