Download !SMOOTH!MUSCLE!

!SMOOTH!MUSCLE!
Where!is!smooth!muscle!
found!in!the!body?!
Smooth!muscle!lines!internal!structures!such!as!the!digestive!
tract!(where!it!propels!gut!contents),!the!lungs!(where!it!
changes!airway!diameter),!and!the!vascular!system!(where!it!
affects!blood!pressure)!
What!do!smooth!muscle!
cells!look!like?!
Smooth!muscle!cells!are!small,!long!and!elongated!and!
approximately!3X5μm!in!diameter!and!200X500μM!long.!They!
have!a!single!nucleus!and!are!nonXstriated.!It!is!involuntary.!
Why!does!smooth!muscle! Smooth!muscle!runs!in!different!directions!in!order!to!shorten!
run!in!different!directions! the!gut!or!squeeze!the!gut.!!
in!the!gut?!
How!can!smooth!muscle!
cells!be!activated?!
What!two!types!of!
smooth!muscle!are!
there?!
Smooth!muscle!cells!can!be!spontaneously!active!(and!contain!
inbuilt!pacemakers),!or!they!can!be!activated!by!nerve!or!
hormonal!stimulation.!!
1. Tonic!smooth!muscle!
2. Phasic!smooth!muscle!
What!is!tonic!smooth!
muscle?!
Tonic!smooth!muscle!is!able!to!maintain!tone!effectively!for!
long!periods!of!time.!It!has!slower!shortening!velocity!than!
phasic!smooth!muscle,!and!displays!no!APs!or!electrical!activity.!
E.g.!maintaining!blood!pressure!
What!is!phasic!smooth!
muscle?!
Phasic!smooth!muscle!maintains!tone!poorly,!but!has!a!
relatively!high!shortening!velocity.!This!means!that!it!is!useful!
for!functions!such!as!peristalsis.!It!is!capable!of!displaying!action!
potentials!and!electrical!activity,!and!can!be!found!in!the!
intestines!and!antrum!of!stomach.!!
What!is!the!time!frame!of!
tonic!vs.!phasic!smooth!
muscle!contraction!
respectively?!
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•
Tonic!smooth!muscle!is!slow!to!contract!
(minutes/hours)!but!can!stay!contracted!for!a!long!time!
(minutes/hours)!
Phasic!smooth!muscle!is!fast!to!contract!(seconds)!but!
doesn’t!stay!contracted!for!long!
How!do!the!autonomic!
innervations!of!tonic!and!
phasic!smooth!muscle!
differ?!
In!tonic!smooth!muscle,!innervation!is!well!developed.!In!phasic!
smooth!muscle,!innervation!is!not!well!developed.!!
If!phasic!smooth!muscle!
is!not!well!innervated,!
how!do!myofibrils!know!
to!contract?!
Phasic!smooth!muscle!(PSM)!cells!are!electrically!connected!via!
gap!junctions.!Thus,!the!tissues!are!able!to!behave!as!a!single!
unit.!Action!potentials!often!start!in!specialized!pacemaker!cells!
and!propagate!that!way.!PSM!also!called!unitary!smooth!muscle!
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What!are!the!
characteristics!of!multi!
unit!versus!unitary!
smooth!muscle?!
!
What!are!the!three!types!
of!action!potential!
waveforms!found!in!
smooth!muscle!and!why!
are!they!shaped!like!this?!! variable!delay!in!opening.!
They!are!shaped!like!this!
because!of!calcium!influx!
and!potassium!outflux!
through!channels!with!
What!is!unique!to!the!
crossXbridge!cycle!in!
smooth!muscle!
compared!to!
skeletal/cardiac!muscle?!
Smooth!muscle!still!has!actin!and!myosin!filaments.!The!actin!
filaments!still!have!tropmoyosin.!However,!there!is!no!troponin!
on!the!thin!filaments!in!smooth!muscle.!Thus,!it!has!a!myosinX
based!control!of!contraction.!!
What!is!different!about!
the!thin!filaments!in!
smooth!muscle?!
No!troponin!proteins!
What!is!different!about!
the!thick!filaments!in!
smooth!muscle!
The!heads!on!the!myosin!contain!light)chains,!one!of!which!is!
essential!for!ATPase!activity!and!the!other!of!which!has!a!
regulatory!function.!They!are!also!arranged!in!a!random!order!
compared!to!skeletal!and!cardiac!muscle,!so!no!striations!occur.!!
How!does!the!lengthX
tension!relationship!in!
smooth!muscle!compare!
to!skeletal!muscle?!
Smooth!muscle!can!be!
stretched!over!a!much!larger!
than!skeletal!muscle!can!and!
maintain!a!significant!ability!
produce!force.!Furthermore,!
ability!of!smooth!muscle!to!
in)situ)is!less!contrained!than!skeletal!muscle.!!
How!can!skeletal!muscle!
exert!force!with!so!much!
contraction!or!stretch?!
Myosin!heads!in!smooth!muscle!move!in!opposite!directions,!
compared!to!skeletal!muscle!where!they!move!in!the!same!
direction.!So,!smooth!muscle!sarcomeres!are!relatively!long.!
Long!sarcomeres!will!generate!as!much!force!as!several!short!
sarcomeres!in!series!in!skeletal!muscle.!Thus,!smooth!muscle!is!
slower!but!more!energy!efficient!than!skeletal!muscle.!!
How!does!calcium!affect!
As!calcium!does!not!bind!to!troponin,!calcium!activation!of!
!
distance!
still!
to!
the!
stretch!
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smooth!muscle!binding?!
What!are!some!pathways!
through!which!
intracellular!Ca2+!(and!
force)!can!rise!in!smooth!
muscle?!
What!is!the!
phospholipase!CXinositol!
triphosphate!pathway!
mechanism,!and!what!
does!it!do?!
What!is!the!mechanism!
through!which!Ca2+!
causes!binding!of!the!
myosin!heads!to!the!thin!
filament?!
Does!the!myosin!head!
automatically!unnatach!
from!the!thin!filament?!
contraction!involves!a!series!of!reactions!on!the!myosin!
filament.!Thus,!generation!of!force!occurs!slower!than!in!
skeletal!muscle,!but!rises!in!cytoplasmic!Ca2+!concentrations!
are!still!responsible!for!the!generation!of!force.!!
1.
2.
3.
4.
Voltage!gated!Ca2+!channels!
Receptor!operated!cation!channels!
Receptor!operatoed!Ca2+!channels!
IP3!pathway!(most!common)!
The!IP3!pathway!is!the!predominant!mechanism!for!increasing!
Ca2+!concentration!in!tonic!smooth!muscle.!!
1.
2.
3.
4.
A!messenger!comes!along!and!activates!a!receptor!
This!receptor!activates!a!Gq!protein!
This!Gq!protein!activates!phospholipase!C!
This!undergoes!a!whole!heap!of!steps,!ultimately!
resulting!in!the!phosphorylation!of!intracellular!proteins!
1. Ca2+!binds!to!calmodulin!
2. This!Ca2+XCalmodulin!then!binds!to!myosin!light!chain!
kinases,!wich!causes!phosphorylation!
3. These!phosphorylates!light!chain!kinases!then!turn!ATP!
into!ADP!
4. With!the!addition!of!ADP,!the!myosin!heads!can!now!
bind!and!contract.!!
5. Thus,!force!is!produced!
No.!Dephosphorylates!myosin!cross!bridges!can!still!remain!
attached!in!a!‘latch!state’.!
What!is!the!summary!of!
all!the!muscle!
contraction!mechanisms?!
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MOTOR!CIRCUITS!AND!REFLEXES !
What!are!some!examples!
of!reflexes?!
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Knee!jerk!
Pupillary!light!response!
Blink!reflex!
Middle!ear!muscle!reflex!
Foot!withdrawal!
What!is!the!spinal!reflex!
pathway?!
!
How!to!the!sensory!signals!
and!motor!reflexes!
integrate!in!a!basic!reflex?!
Within!the!spinal!chord,!somatosensory!afferents!have!axon!
branches!which!synapse!directly!onto!motor!neurons.!This!can!
elicit!a!basic!reflex!without!the!need!for!higher!processing!
area.!
What!are!muscle!spindles?!
Muscle!spindles!are!intrafusal!fibres!wrapped!in!stretch!
sensitive!type!1a!and!type!II!afferent!nerve!endings.!They!run!
parallel!to!larger!extrafusal!muscle!fibres,!and!are!so!small!that!
they!do!not!contribute!to!overall!muscle!force.!
What!do!muscle!spindles!
detect?!
Muscle!spindles!detect!changes!in!muscle!length.!When!a!
stimulus!stretches!a!muscle,!the!muscle!spindle!is!activated!
and!can!cause!a!contraction!od!the!stretched!muscle.!!
What!does!an!afferent!
muscle!spindle!response!to!
length!changes!look!like?!
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It!is!a!dynamic!
response!that!is!
sensitive!to!the!
amplitude!and!
rate!of!stretch.!
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What!happens!to!
surrounding!muscles!when!
a!muscle!spindle!is!
activated?!
• There!is!a!reflex!
contraction!of!muscle!in!the!
response!to!stretch,!and!a!
relaxation!of!antagnostic!
muscle.!!There!is!an!
increase!in!synergistic!
muscle!contraction!and!Ia!
afferent!inhibitory!moto!
neurons!inhibit!motor!
neurions!at!the!antagonist!
muscle.!
Why!do!spinal!reflexes!
occur?!
Reflexes!act!like!negative!feedback!loops!to!control!muscle!
length!or!tension.!However,!they!are!influenced!by!the!
exciteability!of!motor!neurons.!
What!can!regulate!the!
sensitivity!of!muscle!
spindles?!
Gamma!motorneurons!can!regulate!the!sensitivity!of!these!
spindles,!by!regulating!the!slackening!of!the!spindle.!Reducing!
the!slackening!of!the!spindle!means!that!the!spindle!is!
resposnive!even!to!small!changes!in!muscle!length.!!
What!do!the!Golgi!tendon!
organs!do?!
The!golgi!tendon!organs!fire!the!action!potentials!that!are!
caused!by!the!muscle!spindles!
What!is!a!monosynaptic!
stretch!reflex?!
The!monosynaptic!stretch!reflex!is!a!twoXneuron!circuit!(the!
most!basic!of!reflexes!with!one!‘mono’!synapse).!There!is!a!
single!synaptic!connection!between!Ia!afferent!fibers!from!a!
muscle!spindle!and!an!alpha!motor!neuron.!It!provides!a!
negative!feedback!mechanism!for!regulating!muscle!length.!!
What!is!a!Ia!afferent!fiber!
They!are!the!afferent!fibers!that!run!from!the!muscle!spindles!
to!the!CNS.!They!have!a!large!diameter!and!are!fast!to!conduct!
Aps.!
What!is!the!inverse!
myotactic!reflex?!
The!inverse!myotactic!reflex!requires!an!inhibitory!
interneuron.!Stimulation!of!1b!afferents!from!a!golgi!tendon!
organ!causes!reflex!inhibition!of!the!motorneurons!via!a!1b!
inhibitory!interneuron!–!thus!forming!a!negative!feedback!
mechanism!for!regulating!muscle!tension.!!
What!is!a!1b!inhibitory!
interneuron?!
They!are!inhibitory!interneurons!that!receive!also!receive!input!
from!cutaneous!and!joint!sensory!affferents,!which!allow!for!
fine!control!of!delicate!exploratory!movements.!!
What!is!a!Renshaw!cell?!
Renshaw!cells!are!other!inhibitory!interneurons,!which!receive!
input!from!motor!neurons!causing!inhibition!of!the!same!
motor!neurons.!!
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GCPR!AND!SECOND!MESSENGERS !
Which!neuroXtransmitters!
and!receptors!exists!in!
skeletal!muscle?!
Acetylcholine!(Ach)!is!the!neurotransmitter!and!NXcholinergic!
(nicotinic)!receptors!are!the!receptors.!!
What!type!of!channel!are!
nicotinic!receptors?!
LigandXgated!channels!
What!neuroXtransmitters!
act!on!ligand!gated!
channels?!
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•
•
Ach!in!NXcholinergic!(nicotinic)!receptors!
Glutamate!on!the!NMDA!receptor!
Binding!opens!the!channel,!causing!hyper!or!
depolarization!
Where!are!mXcholinergic!
(muscarinic)!receptor!
channels!found?!!
In!the!target!tissue.!They!response!to!Ach.!They!are!not!ligand!
gated!ion!channels.!!
Activation!of!which!
receptors!increases!
heartrate?!
Stimulating!cardiac!β1Xreceptors!increases!the!heart!rate!
What!does!adrenaline!do!
in!the!body?!
Adrenaline!causes!glycogen!breakdown!in!skeletal!muscle.!!
What!are!GPCRs?!
GPCRs!are!GXprotein!coupled!receptors.!It!is!a!transmembrane!
protein!that!binds!hormone!or!neurotransmitter!on!the!
extracellular!side!and!when!activated!binds!to!heterotrimic!GX
proteins!
What!do!GXproteins!bind!
to!on!the!intracellular!side!
and!how!does!this!affect!
the!GXprotein.!
GXproteins!bind!to!guanine!diphosphate!(GDP)!and!guanine!
triphosphate!(GTP).!The!GXprotein!is!inactive!when!bound!to!
GDP,!however!binding!to!a!neurotransmitter/hormone!such!as!
Ach!on!the!extracellular!side!causes!the!GXprotein!to!spit!of!
GDP!and!take!up!GTP,!which!causes!it!to!enter!its!active!state.!
What!happens!to!the!
activated!GXprotein?!
The!activated!GXprotein!dissociates!from!the!receptor!and!
then!dissociates!into!two!separate!units:!(1)!the!α!subunit!and!
(2)!the!β!and!γ!subunits.!!
What!does!the!α!subunit!
do?!
The!α!subunit!binds!to!membrane!bound!enzymes!which!
produce!second!messengers!and!activates!them.!These!second!
messengers!then!move!into!the!cytosol!
What!are!the!three!main!
types!of!GXproteins?!
Gs!for!GXstimulatory,!Gi!for!GXinhibitory,!and!Gq!for!GXqueer.!!
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