Smooth muscle excitation contraction coupling

Smooth muscle excitation contraction coupling


okay in this video we’re going to look
at the excitation contraction coupling process
for smooth muscle smooth muscle is a little
bit more complicated than skeletal muscle only
because there’s a lot more ways to get
calcium levels to go up in the cytosol. What is the same as with
skeletal muscle and as we’ll see later with cardiac muscle is that increased
levels of cytosolic calcium are needed for contraction, lower levels
of calcium mean less contraction so let’s start with just orienting
ourselves to do this diagram. So this yellow line here is
representing the plasma membrane or sarcolemma of smooth muscle and on that membrane is a calcium ATPase which pumps
calcium out. We’ll come back to that later, and of course we have a calcium channel with various gating mechanism, so as you have
read in your notes it could be a change in voltage, mechanical stretch
or a ligand binding, or this could be a receptor that’s connected to other proteins and a second messenger
system Activation of that second
messenger system results in increased levels of cytosolic
calcium And then we have our sarcoplasmic
reticulum here, the SR, storing lots of calcium in it
and again a calcium ATPase to put calcium back Okay let’s start with something coming
along and opening this calcium channel and let’s pretend it’s a mechanically gated
calcium channel so some stretch, so maybe we’re in a blood vessel, or in the bladder and it opened and calcium entered, and when calcium enters the cytosol of smooth muscle, it binds with the
regulatory protein called calmodulin so when there’s no calcium in the
cytosol calmodulin just hangs out doesn’t do anything, but then calcium binds to calmodulin and this is very similar in structure to
troponin, and this calcium-calmodulin complex activates another protein So there’s another protein called myosin
light chain kinase. So we have inactive myosin light chain kinase and it just hangs out does nothing until calcium-calmodulin comes along and
then we have active myosin light chain kinase, and what this does, -it’s a kinase right – so it adds a
phosphate to something and what it does is it adds a phosphate
to myosin So here we have myosin light chain kinase
once it’s been activated by calcium calmodulin takes an inactive myosin and adds a phosphate to it Now we have active myosin so this is really kind of different from
skeletal muscle where myosin is always capable of being
active it’s just waiting for the binding site
of actin to be revealed with smooth muscle, the binding site of actin is always available but myosin is not active until it has
another phosphate added to it and then once
myosin is active it’s able to go through the cross
bridge cycle and then we say cross bridge cycle
starts which is pretty much the same as in
skeletal muscle once myosin has become activated by having an extra phosphate added to it.
Well what stops the contractions? So myosin gets activated, undergoes the crossbridge cycle. Well
there’s another enzyme that is always working opposing the activity of
myosin light chain kinase and that is myosin phosphatase and what that does is removes a phosphate so there’s a war going on between myosin kinase and myosin phosphatase so myosin phosphatase is always always
always active and it’s constantly taking the
phosphates off myosin to inactivate and my supply chain kind
eases owns adding the phosphate to it as long as it is
active so what that means is to have active
myosin light chain kinase adding phosphate to myosin allowing it to
undergo the crossbridge cycle you have to have calcium-calmodulin present, and to have calcium calmodulin you have to have calcium. So in order to have contraction you have have to have myosin kinase more active then the myosin phosphatase
otherwise you have relaxation happening so for contraction MLCK activity has to be greater then myosin phosphatase activity so it’s really a graded response because the amount minus kinase activity
depends on how much calcium- calmodulin its present and
that depends on how much calcium got let into the cytosol, so you have graded response to calcium. A little bit of
calcium gives you a little bit of contraction A lot of calcium gives you a lot contraction So again we always have to be talking
about how do we stop the signal and stop the
contractions from happening Well there’s a couple of things.
Obviously myosin phosphatase activity is always opposing mysoin kinase so trying to cause relaxation to happen but
if calcium stops getting let in to the cytosol, we close calcium
channels then calcium in order to get rid of
calcium we have to pump it out against its concentration gradient so
that means we can pump it out into the interstitial fluid across the sarcolemma using calcium
ATPase for it to get pumped back into the
sarcoplasmic reticulum so what’s the role of the sarcoplasmic
reticulum how does calcium get outof this Well it depends you can have for example a protein here it’s attached to another
protein here and a ligand will bind to it that’s a ligand, and that will activate another protein that will end up letting calcium out, so a second messenger
system pathway can result in calcium being let out of the sarcoplasmic reticulum
and we’re not going to worry about the details of those mechanisms but just be aware that it’s not always
a ligand-gated channel directly increasing
the calcium in the cytosol but it could be a be a ligand binding with a receptor attached to a second messenger
system resulting in increased levels of calcium The point is though that the more
calcium that’s in the cytosol the stronger the force of
contraction, less calcium leads to a lower force of
contraction and there’s a lot of therapeutic drugs that
influence the state contraction of smooth muscle and some of them influence channels, some of them
might influences these receptor proteins, some of
them might influence the state of myosin light chain kinase or even influence mysoin phosphatase. So the process is a little more complicated than skeletal muscle but we can make it pretty straightforward
if we remember that calcium linked to increased levels
of myosin kinase activity, lower levels of calcium linked with lower levels of myosin kinase activity, and of course to get
contraction, myosin kinase activity has to be higher then
myosin phosphatase activity Okay I hope that this is clear. Another place to look at this is in your
textbook figure 12-26 has a slightly different version of this drawing if you want to take a look at that

58 Replies to “Smooth muscle excitation contraction coupling”

  1. Great video but how do you explain the active calmoduline's inactivation, further I beleive it's not Phosphotetraoxid (PO4) but ATP which is used by MLCK (kinases in general use ATP)

  2. Is there still ADP and Pi that is binded to the myosin head as it does in skeletal? Or is it just the phosphatase that brings the myosin head back to rest and therefore to be another powerstroke, the myosin head needs to be phosphorylated again? 

  3. thank you very much! i sat through a 2 hour lecture and didn't understand a thing and you just put it together in under 10 minutes! thank you!

  4. in my text book  the sequence of events in contraction and relaxation of visceral smooth muscle  started with (binding of acetylcholine to muscarinic receptors) then (increased influx of Ca into the cell) does that mean when Ach bound to muscarinic R made the influx of Ca ions increased ???
      
    and they mentioned dephosphorylation of myosin by myosin light chain phosphatase not only (myosin phosphatase) or is it the same???

  5. In the skeletal muscle there is a movement of the myosin in relation to the actin. 
    here you only describe the part in which the myosin is attached to the actin, but how does he move?
    does it use ATP to release the actin? or does it release the actin only when the levels of MLCK decrease and the myosin is dephosphorylated?
    thanks.

  6. Where does caldesmon and calponin fit in? I know smooth muscle doesn't have troponin, though it has tropomyosin (which ought to inactive the binding sites, right?), do they function to fill that role on the actin filament in lieu of the troponin somehow? Thanks for the video and your time!

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