Muscle IX Flashcards
What are action potentials in smooth muscle initiated by
Neural, hormonal, or mechanical stimulation
Where do APs occur in smooth muscle
Unitary smooth muscle
What are two types of smooth muscle autonomic AP patterns
Some spiky and some plateau
- always have same type
- if spiking always spiking
Why is smooth muscle APs longer
- Upstroke slower because CA channels propagate AP not Na
- Repolarization slower because Ca channels inactivate slowly and there is delayed activation of voltage gated K+ and Ca activated K+ channels
Two types of membrane potentials with spontaneous activity
Slow wave potentials and pacemaker potentials
Slow wave potentials
Fire APs when reach threshold
- slow depolarization and repolarization with additional input will bring to threshold
Pacemaker potentials
Always depolarize to threshold
- continuous firing of APs
What causes contraction in smooth muscle without APs
In response to graded depolarizations
- some membrane potential oscillations can lead to tonic contractions in absence of APs
What smooth muscle does not have APs
Multi unit smooth muscle
- graded response
- autonomic neurons create local depolarization that spreads in graded fashion throughout muscle fiber triggering Ca entry
What is contraction due to electrical signaling
Electromechanical coupling
What are the 3 mechanisms that increase ECF entry and ICF release of Calcium and activate contraction
- Ca entry through voltage gated channels or ligand gated ion channels
- Ca release from SR
- Ca entry through voltage independent channels
What are 2 mechanisms of Ca release from SR
- Ca induced Ca release from RyR (have DHP receptors but not mechanically coupled)
- IP3 Ca release from IP3R
What are the voltage independent channels in smooth muscle
- store operated Ca channels
- stretch activated channels
What type of voltage gated channels allow Ca entry in smooth muscle
Voltage gated L-type Ca channels
How does Ca release from SR in smooth muscle
Less SR
- via ca induced ca release and IP3 pathways
- ca enters from L-type channels and bind to RyR to release from SR
What can IP3 pathway cause
Contraction and increase in Ca without change in membrane potential or very little
What are store-operant channels
Depletion of Ca in SR causes activation
Causes Ca influx across membrane
Allows Ca to remain elevated and replenish SR
What is pharmomechanical coupling
Ca release from SR via IP3 and entry of CA via store operant channels are voltage independent
Occurs when chemical signals change muscle tension with little or no change in membrane potential
What can induce smooth muscle contraction independent of AP generation
Drugs, excitatory neurotransmitters and hormones
How does stretch activated contraction work
Stretch causes internal release of Ca from SR through RyR
Stretch shown to cause phosphorylation of myosin light chain leading to contraction
What is Ca signal in smooth muscle
Ca initiates slow chain of events increasing myosin ATPase activity
- turns on myosin head
How is myosin ATPase activated in smooth muscle
Low activity at rest
Requires phosphorylation of regulatory light chain to turn on myosin ATPase to hydrolyze ATP
How is myosin ATPase activity increased in smooth muscle
4 Ca ions bind to calmodulin
When Ca concentration increases calmodulin binds to Ca
When decreases calmodulin releases Ca
What is calmodulin
Calcium binding protein similar to troponin C of striated muscle
Initiation of cross bridge cycling in smooth muscle when Ca bound to calmodulin
- Ca-calmodulin complex activated myosin light chain kinase
- MLCK phosphorylation regulatory light chain near myosin head
- Alter conformation of myosin head, increasing ATPase activity and allowed it to interact with actin
The smooth muscle cross bridge cycle primarily activates what
thick filaments
What does increased Ca entering during graded contractions cause
More calmodulin acitvated
Increased MLCK activated
More myosin heads activated
Increased force generated
What is difference between cross bridge cycling in smooth and cardiac/skeletal muscle
Occurs more slowly in smooth
- hydrolysis and release of ADP slower
- shortening and tension occurs over several seconds
Cross bridge cycling similar in all muscle types what is difference in smooth
Regulatory light chain must be phosphorylated
What causes relaxation in smooth
1.Ca moved back to SR and extracellular space
2. Regulatory light chain but also be dephosphorylated by myosin light chain phosphatase
3. Some muscle can maintain force after dephosphorylation for extended period of time with little ATP (latch state)
What does myosin light chain phosphatase do
Removes phosphate groups on regulatory light chain leading to relaxation
What is latch state
Unknown process
- why smooth can maintain contraction with very little ATP and fatigue
- myosin already bound to actin when dephosphorylation occurs
What is force of contraction a balance of
Kinase phosphorylation regulatory light chain vs phosphatase dephosphorylating
What can alter smooth muscle Ca sensitivity
Neurotransmitters, hormones, and paracrine molecules by modulating myosin light chain phosphatase
How do you generate more force in smooth
Low phosphatase activity sensitized myosin
- inhibiting MLCP or activating MLCK leading to greater contraction at lower Ca
