Smooth Muscle Lecture Flashcards
Explain the sequence of molecular events in contraction of smooth muscle
AP in smooth muscle membrane causes the opening of voltage sensitive calcium channels. This increases the level of calcium. Calcium then binds to calmodulin (which activates calmodulin). Ca-binded calmodulin then activates myosin light chain kinase, which phosphorylates myosin. Then Myosin-P and actin bind, cross bridges form and produce tension, using ATP. When non-phosphorylated myosin and actin bind, latch bridges form but do not cycle aka do not use ATP (a tonic level of tension is produced). Note: myosin light chain kinase phosphorylating myosin makes myosin more active
In smooth muscle: Thick filament is regulated by ________.
Explain the difference between phasic and tonic contractions.
Thick filament is regulated by myosin light chain kinase (MLCK).
Phasic is the contraction created by MLCK.
Force is often maintained long after calcium has declined to baseline (formation of latch crossbridges, low energetic state, allows for maintained contraction without the use of ATP).
Such contractions can be energetically effecient because crossbridges are not cycling (not using ATP) but stay latched for long times. If MLC is dephosphorylated while attached, detachment is very slow, accounting for this “latch state”
Explain and Diagram the smooth muscle E-C coupling mechanisms involving voltage gated, ligand gated, and IP3 gated Ca channels.
AKA what are the three fundamental pathways that affect the calcium level in the cytosol of smooth muscle
Calcium is the signal molecule responsible for the activation of contractile proteins in smooth muscle (just like striated muscle, BUT the mechanism of activation is different.) DOES NOT INVOLVE TROPONIN OR THIN FILAMENT REGULATION. Does involve tropomyosin.
There are three fundamental pathways that affect Ca level in the cytosol of smooth muscle.
- hormone or NT receptor activation leads to formation of IP3 that goes and binds directly to the SR, that triggers release of calcium from SR (g protein coupled response)
- opening of voltage controlled calcium channel (L-type) results in influx of calcium through the plasma membrane (controlled by membrane potential)
- Hormone or NT receptor activation results in opening of ligand coupled calcium channel resulting in influx of calcium through plasma membrane.
NOTE: Pathways 1 (IP3) and pathway 3 (hormone/NT resulting in opening of calcium channel in PM) can both happen without a change in the membrane potential
What does Rho-Kinase do?
Rho kinase enhances the activity of myosin light chain kinase. It also inhibits the myosin phosphotase complex and the CPI protein (which inhibits the phosphotase).
Helps with activating smooth muscle contraction
What is pharmomechanical coupling?
Pharmomechanical coupling is changes in force resulting from a drug or hormone that has NO significant effect whatsoever on the membrane potential.
What are the pathways of smooth muscle activation that DO NOT require deplorization?
- IP3 causes release of calcium from the SR, leading to MLCK dependent contraction via Ca-CLM
- cAMP activates PKA, which phosphorlyates MLCK, decreasing its calcium sensitivity, ALSO increases SR calcium pumping: relaxation
- cGMP stimulates MLKphosphotase, decreasing myofilament activation… RELAX
What are the pathways of smooth muscle activation that DO require alterations in the membrane potential?
- Voltage gated Ca channel
- Ligand bound Ca channel. sufficiently activate voltage gated calcium channel
- Moderate depolarizations of RMP activate small tonic amounts of ca current that can keep intracellular ca high
- Ca entry leads to Ca-CaM and MLCK, but can also be amplified by CICR
- Spread of depolarizations via gap junctions is important in single unit activation
What does Rho Kinase do?
Essentially, it enhances the activity of MLCK.
It phosphorylates MLC
It phosphorylates the phosphotase (inactivates it)
It also phosphorylates CPI, which inhibits the phosphotase as well
Draw the graph of contraction by MLC phosphorlyation as a function of Ca graph.
Draw the graph, explain which each side means
Left shift means increased Ca sensitization and low phosphotase activity
Rightward shift means decreased Ca sensitivity and high phosphotase activity
What is the latch state?
The term latch state refers to the condition of tonic contraction during which force is maintained at low energy expenditure.
In the endothelial cells, ACh triggers the relase of ____ which causes ____ of tissue.
Endothelial cells secrete NO. So in endothelial cells, ACh triggers the relase of NO which causes relaxation.
In smooth muscle, Vo is directly dependent on ____________. Active fore rises rapidly with _____.
In smooth muscle Vo is directly dependent on cross bridge phosphorylation by MLCK.
Active force rises rapidly with phosphorylation.
