Smooth Muscle Contraction Flashcards
1
Q
organization of smooth muscle
A
- thick and thin filaments
- no sarcomere
- thin filaments anchored to cytoskeletal dense body
- lack A and I bands
- not striated
- no T tubules
- SR less elaborate
2
Q
smooth muscle contractions
A
- contractions and relaxations are slow but muscle shortens a lot
- less than 1/3 of original resting length
3
Q
caveoli
A
- space where lots of signaling occurs
- pressed up against SR in these places
- enriched with cell receptors and ion channels
- muscarinic Ach receptors
- L type Ca channels, ATP sensitive K channels, Ca sensitive K channels
4
Q
temporal relationship
A
- similar to skeletal
- onset of contraction is slower and duration of tension is usually longer
- unlike Na dependent AP, AP is Ca dependent
5
Q
multiunit
A
- discrete smooth muscle fibers
- each one innervated by single nerve endings
- contraction seldom spontaneous
- ciliary muscle and iris of eye
- piloerector muscles cause erection of hairs via SNS
- don’t respond to stretch
- neural factors control contraction
- airway
6
Q
unitary
A
- electrically coupled via gap junctions and can be spontaneously active
- unitary-millions of smooth muscle cells organized in sheets or bundles contract in a coordinated fashion
- respond to stretch but not SNS
- small BV, GI tract, uterus
7
Q
smooth muscle contraction mechanism
A
- extracellular and SR ca
- AP depolarizes sarcolemma, influx of Ca through L type channels- this Ca causes CICR from SR
- can also be released after agonist binding to Gq,activating phospholipase C, cleaving PIP2 into DAG and IP3, IP3 binds to receptor in SR and causes release
- contraction caused by increased [ ] of Ca that diffuses to contractile filaments
- reducing contraction can occur by blocking L type channels
- Ca removed by pumps in SR membrane and PM, and by exchange across PM
- capacitive calcium entry-SR refilled from outside cell- but doesn’t trigger contraction
8
Q
myosin light chain kinase
A
- Ca released from SR binds to calmodulin
- Ca calmodulin complex binds to MLCK
- MLCK phosphorylates the regulatory light chain of myosin
- conformational change of myosin allows interaction with actin
- MLCP is a phosphatase that removes P to inactivate myosin
- reduction of calcium also causes relaxation
9
Q
summary of smooth muscle contraction
A
- electromechanical stim-AP or stretch-Ca channel opening +
- pharmacomechanical- ligand binds and activates G protein—>
- increase in intracellular Ca
- CICR
- Ca-Calmodulin activation of MLCK
- contraction
10
Q
smooth muscle activation
A
- spontaneous in intestine, stomach, colon, uterine
- uterus at term develops synchronous contractions and pacemakers with diastolic depolarizations
- vascular smooth muscle contracts in response to excitation by stretch, sdrenergic neurons, endo cells, chemical factors
11
Q
membrane potential
A
- resting potential of smooth muscle is -50- -60
- spike AP in unitary are short duration relative to contraction time-contract longer
- depolarization caused by inward Ca, repol by K
- some visceral smooth muscle exhibits slow waves that initiate superimposed spike potentials
- uterine smooth muscle APs have plateaus
12
Q
basal electric rhythm
A
- rhythmic depol of intestinal smooth muscle
- originate at a specific point and are propagated along the length of the GI tract
- determine contractile parameters of stomach as a whole, maximal freq, propagation velocity, and direction
- pacemaker activity in interstitial cells of Cajal are not sufficient to initial AP in smooth muscle
- release of neurotransmitters from enteric nerve endings plus the basal waves causes AP leading to contraction
- various patterns can be accomplished depending on if stomach is filled, or fasted
- stomach is 3 per min, duodenum 12 per min
13
Q
smooth muscle cross bridge cycle
A
- Ca enters cells as discussed- channels/CICR/ IP3 gets Ca from SR
- calmodulin calcium complex binds to MLCK and activates that which P myosin light chain (in addition to P already there)
- myosin with 2 phosphates binds actin
- releases head Pi for stroke
- ATP binds to release from actin
- ATP hydrolyzed leaving ADP on head
- as long as MLCK active, this keeps going, if MLCP takes off P, cycle stops
- if low Ca but still presence of ATP, the MLCP can take of second P and myosin is latched to actin-maintains tension
14
Q
endothelin
A
- 21 amino acid peptide produced by vascular endo from 39 aa precursor by endothelin converting enzyme (inhibited by NO)
- formation and release stimulated by angiotensin II and ADH, thrombin, cytokines, ROS, and shearing forces
- once released, binds to ETB in endothelium first, which causes NO to be made from L-arg and NOS, the NO causes increase in cGMP which causes relaxation of vascular smooth muscle (dilation)
- next binds to ETB and A in smooth muscle, which are coupled to Gq- PLC generates IP3 and Ca- which causes contraction of the vascular smooth muscle
- increases contractility of the heart and HR
15
Q
cardiovascular effects of endothelin
A
- ET1 causes transient vasodilation (by initially binding to ETB in endothelium and causing NO to be made, NO inc cGMP) and hypotension
- followed by prolonged vasoconstriction and hypertension
16
Q
diseases associated with elevated endothelin
A
- hypertension, coronary vasospasm, heart failure
- in heart failure, ET1 released by failing myocardium, contributes to Ca overload and hypertrophy
- endothelin receptor antagonists decrease mortality and improve hemodynamics
17
Q
epi and contraction in fight or flight
A
- contracts skin arteriolar SM and gut arteriolar SM-need blood other places
- epi binds to a1 receptor in smooth muscle
- coupled to Gq–>PLC–>IP3–> Ca–>ca/calmodulin–>MLCK–>contraction
18
Q
epi and relaxation in fight or flight
A
- stimulates relaxation in skeletal arteriolar SM, heart muscle arteriolar SM, bronchiolar smooth muscle-need blood there
- epi binds to b2 receptor
- coupled to Gs, increases cAMP, activates PKA, which inhibits MLCK by P it
- MLCK-P can’t be stimulated by Ca/calmodulin, no myosin phosphorylation
- relaxation
19
Q
acute control of blood flow
A
- rapid changes in local vasodilation or vasoconstriction of the arterioles, metarterioles, precapillary sphincters
- occurs within seconds to minutes
- rapid maintenance of appropriate local tissue blood flow
- increases as met increases and as oxygen saturation decreases
20
Q
when availability of oxygen decreases
A
- high altitude
- pneumonia
- CO poisoning
- cyanide poisoning
- blood flow increases markedly
21
Q
two theories for hyperemia
A
- low oxygen causes smooth muscle relaxation of sphincter-more blood
- substances including adenosine are released by active muscle and cause relaxation of sphincter
- increase in met causes tissue eating and release of vasodilator substances-adenosine, K, histamine, hydrogen
22
Q
adenosine receptors
A
- nucleotide
- adenosine binds A1, A2A, and A3B adenosine G protein coupled receptors in smooth muscle
23
Q
A1 adenosine receptors
A
- couple to ATP sensitive K channels
- cause smooth muscle hyperpolarization and a decrease of calcium influx
- relaxation
24
Q
A2 adenosine receptors
A
- couple to Gs
- activates adenylate cyclase
- activates PKA
- P on MLCK
- inactivates MLCK so it can’t respond to Ca/calmodulin and can’t P myosin
- causes relaxation
25
Q
stress relaxation of smooth muscle
A
- passive decline in tension over time due to physical properties of tissue
- bladder doesnt hurt anymore even though you didn’t empty it
- related to viscoelastic properties
26
Q
active smooth muscle relaxation
A
- stretch receptors in the stomach and duodenum trigger neurotransmitter release that stimulates smooth muscle relaxation
- vago-vagal and intrinsic reflexes
- Ach released by vagal pathways acts presynaptically to release additional neurotransmitters that relax gastric smooth muscle layers in proximal stomach
- VIP and NP
27
Q
active smooth muscle relaxation by agonists
A
*as opposed to Ca decrease or activating PKA to deactivate MLCK
- NO released by autonomic neuron and the endothelial cells lining blood vessels
- neuron releases NO, diffuses to smooth muscle
- Ach binds to M3, muscarinic receptor, leading to more NO diffusing to smooth muscle cell
- both sources of NO activate guanylyl cyclase and increase cGMP in smooth muscle
- cGMP activates CGMP dependent protein kinase I which elevates MLCP activity
- decreases myosin activity-relaxation
- second phase-VIP binds to receptors in smooth muscle and causes delayed relaxation through an increase in cAMP or decrease in Ca
28
Q
so many mechanisms?
A
- downstream effect of many system wide processes
- signals produced during other processes will cause vascular response by directly controlling relaxation or contraction
