3.Smooth muscle contraction.pdfsgsgdgfdgh

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1. Smooth muscle

2. Smooth muscle
•Smoothmuscleshavemolecularstructuressimilartothoseinstriated
muscle,butthesarcomeresarenotalignedsoastogeneratethestriated
appearance.
•Smoothmusclescontainα-actininandtropomyosinmolecules,asdo
skeletalmuscles.
•Theydonothavethetroponinsystem,andthelightchainsofsmooth
musclemyosinmoleculesdifferfromthoseofstriatedmusclemyosin.
•Regulationofsmoothmusclecontractionismyosin-based,unlikestriated
muscle,whichisactinbased.
•However,likestriatedmuscle,smoothmusclecontractionisregulatedby
Ca2+.

5. Smooth muscle contraction
•Smoothmusclecontractionis
dependentoncalciuminflux.
•Calciumisincreasedwithinthe
smoothmusclecellthroughtwo
differentprocesses.
•First,depolarization,hormones,or
neurotransmitterscausecalcium
toenterthecellthroughL-type
channelslocatedinthemembrane.
•Intracellularcalciumthenstimulates
thereleaseofcalciumfromthe
sarcoplasmicreticulum(SR)byway
ofryanodinereceptorsandIP3;this
processisreferredtoascalcium-
inducedcalciumrelease

6. •Oncecalciumhasenteredthe
cellitisfreetobind
calmodulin,whichtransforms
intoactivatedcalmodulin.
•Calmodulinthenactivatesthe
enzymemyosinlightchain
kinase(MLCK),MLCKthen
phosphorylatesaregulatory
lightchainonmyosin.
•Oncephosphorylationhas
occurred,aconformational
changetakesplaceinthe
myosinhead;thisincreases
myosinATPaseactivitywhich
promotes interaction
betweenthemyosinheadand
actin.

7. •ATPaseactivityismuchlowerin
smoothmusclethanitisinskeletal
muscle.
•Thisfactorleadstothemuchslower
cyclingspeedofsmoothmuscle.
•Smoothmusclecontractionis
enhancedevenfurtherthroughthe
useofconnexins.Connexinsallowfor
intercellularcommunicationby
allowingcalciumandother
moleculestoflowtoneighboring
smoothmusclecells.
VGCC-voltage gated Ca2+ channel

8. Smooth muscle relaxation
•Relaxationofsmoothmuscle.Smooth
musclerelaxationoccurseitherasaresultof
removalofthecontractilestimulusorbythe
directactionofasubstancethatstimulates
inhibitionofthecontractilemechanism.
•Regardless,theprocessofrelaxation
requiresadecreasedintracellular
Ca
2+
concentrationandincreasedMLC
phosphatase(myosinlightchain
phosphatase)activity.
•Thesarcoplasmicreticulumandtheplasma
membranecontainCa,Mg-ATPasesthat
removeCa
2+
fromthecytosol.
•Na
+
/Ca
2+
exchangersarealsolocatedonthe
plasmamembraneandaidindecreasing
intracellularCa
2+
.Duringrelaxation,
receptor- and voltage-operated
Ca
2+
channelsintheplasmamembrane
closeresultinginareducedCa
2+
entryinto
thecell.

9. Nitric oxide role in smooth muscle
contraction
•Anotherimportantclinicalaspectofsmooth
musclerelaxationisthemechanismofnitric
oxide.
•Nitricoxideisformedvianitricoxidesynthasein
endothelialcells;itisthenabletodiffuseoutof
theendotheliumintosmoothmusclecells.
•Nitricoxidetheninducestheconversionof
guanosinetriphosphate(GTP)tocyclic
guanosinemonophosphate(cGMP)bybindingto
andactivatingtheenzymeguanylylcyclase.
•Insmoothmusclecells,theincreaseincGMP
willleadtostimulationofcGMP-dependent
proteinkinasewhichinturnactivatesMLCP
(myosinlightchainphosphatase),leadingto
dephosphorylationofmyosinlightchainsand
eventualsmoothmusclerelaxation.

10. Contraction
•Rise in intracellular calcium ions (Ca2+)
•action potential depolarizes plasma
membrane
•L-type voltage-gated Ca2+ channels open,
causing intracellular Ca2+ levels to rise
•Ca2+ are sequestered in sarcoplasmic
reticulum inside the cell
•when excited, Ca2+ channels on sarcoplasmic
reticulum membrane open
•free Ca2+ are released into the cytoplasm
•Ca2+ bind to calmodulin, which induces
conformational change
•Ca2+-calmodulin(CaM) complex activates
the myosin light-chain kinase (MLCK)
•this phosphorylates myosin light chain (MLC)
and triggers actin-myosin binding and
smooth muscle contraction
Relaxation
•Nitric oxide
•nitric oxide is a soluble guanylyl
cyclase that produces cyclic
guanosine monophosphate
(cGMP)
•cGMP activates protein kinase G,
which activates MLCP
•Myosin light chain phosphatase
(MLCP)
•dephosphorylates and inactivates
MLC allowing the myofibrils to
relax