So let’s go through the full process of how
calcium causes the muscle to contract.
And to give you a little
compare and contrast,
we’ll use skeletal muscle
as our contrasting agent.
So you start off with calcium,
you end up with a contraction.
So let’s go through
Smooth muscle, calcium
binds to calmodulin,
which then activates
myosin light chain kinase,
which phosphorylates myosin,
which then causes actin-myosin
cycling, and contraction.
In skeletal muscle, calcium
binds to troponin, which
moves tropomyosin off the
active site on actin.
Once actin is available,
myosin-actin interactions occur,
crossbridge cycling happens,
and you get a contraction.
So those are the overall
pathways between striated
muscle contraction and
smooth muscle contraction.
Now, let’s break each one
of these parts down.
So, once we have
if we are in smooth muscle,
we’re binding to calmodulin.
In skeletal muscle, striated
muscle, we’re using troponin.
So both of these are the
but they are different depending upon
which tissue we’re talking about.
Their activation also activates
a different molecule.
In terms of striated muscle, troponin
moves tropomyosin off of an active site.
In terms of smooth muscle, calmodulin
activates myosin light chain kinase.
The interesting thing about
these two differences is myosin
light chain kinase is known
as thick filament regulation,
while the movement of troponin
is thin filament regulation.
So what is the think filament?
What’s the thin filament?
In terms of smooth muscle,
you get myosin light
chain kinase to
and in terms of skeletal muscle, you get
tropomyosin to move off of a binding site.
So now let’s talk about the
So myosin is what is being
regulated on smooth muscle,
actin is what’s being
regulated in skeletal muscle.
Both of these allow for the same
kind of contraction process.
You need to have an interaction
between actin and myosin no matter
if you go from the myosin point of
view or the actin point of view.
This will then lead to
which is what causes a
muscle contraction to occur.
So some of the parts between skeletal
muscle and smooth muscle are similar,
but how you get to the activation
portion is what is different.
The nice thing about using the
smooth muscle contraction mechanism
is not only is it gradiated, meaning that
you can have large amounts of forces
or small, but also it is a less vigorous
and less rapid type of contraction.
Striated muscle or
skeletal muscle usually is
relatively fast and can
have a high rate of force.
So let’s now talk about crossbridge
cycling in smooth muscle specifically.
You have light chains on myosin.
You have a binding site
for inorganic phosphate.
You have a binding site for ADP.
Once you have calcium binding to calmodulin,
it activates myosin light chain kinase.
If you activate myosin
light chain kinase,
you will get crossbridge cycling
to want to start to occur.
Then you get binding of the myosin
head to the active site on actin.
You lose the inorganic
phosphate and the ADP.
ATP then binds here.
And finally, you’ve gone through the whole cycle.
But that binding, small
movement, unbinding, binding,
small movement, unbinding is
characteristic of crossbridge cycling.
Now, what regulates
There are two primary enzymes.
So far, we’ve only talked about myosin light
chain kinase and that’s denoted here.
But there’s another enzyme
that we need to make sure
that we’re aware of, and
that’s myosin phosphatase.
So myosin phosphatase’s
role is to inhibit myosin,
while myosin light chain
kinase is to activate it.
Okay. So let’s go through a
couple of examples of how we can
use one or the other enzyme to
facilitate muscle contraction.
So, myosin light chain kinase,
the normal activator of myosin,
it will activate myosin
to undergo contraction.
Now a number of processes
affect myosin phosphatase.
Protein kinase C is a
Also, rho kinase is a
So this is where it
gets a little complex.
So protein kinase C and rho kinase
both inhibit myosin phosphatase.
If you inhibit an
inhibitor, you activate it.
So, you can just think
about the two inhibitors
kind of cross-canceling
each other out.
So you inhibit an inhibitor, you
stimulate muscle contraction,
and that can be seen here.
The other portion of
regulating smooth muscle
contraction is the formation
of a latch-bridge state.
So oftentimes what a latch-bridge is, is
to let myosin still be connected to actin,
but not allowing
it to fully relax.
This creates a little bit
of tension in the muscle,
but doesn’t start
So if you think about
this, why in the world
would you want to cause
a latch-bridge state?
Hopefully, what came to mind is,
well, is there a time where you
wanted to maintain tonic contraction,
but not spend a lot of energy?
You can maybe cause a little
contraction and kind of lock it there
and that will maintain tension for
a longer period of time without
continually using ATP or energy
to do that particular process.
There are many times
that that’s important.
One of which could be
something like a sphincter.
If you want to have a sphincter
contracted for a long period of time,
would you always want to tell it,
“Contract, contract, contract, contract,”
or would you simple have it contract
and lock in that contracted state?
That will save energy but
still maintain its function.
Now, let’s move from contraction
of smooth muscle to relaxation.
The key to relaxation of smooth
muscle is to get rid of the calcium
because calcium is activating calmodulin,
which starts that whole process.
So if you can get rid of calcium, you’re
going to be able to relax the smooth muscle.
There are two ways in
which you can do this.
One is you can push calcium
outside of the cell.
So this is extruding
calcium out of the cell.
How do you do that?
Either with a calcium ATPase,
which is calcium pump,
or a sodium-calcium exchanger
Both of these will do the same function
of removing calcium from the cytosol.
Again, if you remove calcium
from the cytosol, it will relax.
The other way you can do that is to
sequester calcium back into the SR.
And remember, the SR is the
This can be done by a couple of
mechanism, one is you can move calcium
from outside the cell directly into
the SR with store-operated channels.
Another way you can do that is by using
this specific sarcoplasmic reticulum
calcium pump and that will pump calcium
directly from the cytosol into the SR.
And so remember, the SR is simply a
partitioned portion of the cell.
If calcium is not in the
cytosol or in the free
portion of the cell, it
won’t undergo contraction.
So if you sequester
it within any locale,
think of it as moving it into a
closet and closing the door.
That way you can
keep calcium around,
but it’s just not messing
everything up in the living room.