Greetings.

Today we're going to continue our

discussion of muscle, and we want to
particularly talk about smooth muscle.
Smooth muscle is an involuntary muscle,
that is regulated by the autonomic nervous
system.
Smooth muscle has some special properties
about it, that differ very significantly
from striated muscle, which is both
skeletal muscle and cardiac muscle.
One of those is that smooth muscle
actually can divide throughout the life of
the organism.
And secondly, that it will change in size,
so that if you have increase in mechanical
work, smooth muscle will get fatter or it
will get longer.
So the smooth muscle has both hypertrophy
as well as hyperplasia.
The smooth muscle is found around the
walls of the blood vessels, and it's found
in the walls of the visceral organs.
The smooth muscle, like other muscles,
does in fact have 3 of the, of, of 3 very
important principles.
And the first is, is that the smooth
muscle will use the sliding filament
mechanism for contraction.
This is where we have myosin filaments are
going to be walking past the actin
filaments and drawing the actin filaments
closer together.
The second thing is that the myosin and
actin interactions are going to be
governed by calcium.
So, in order to get an, a contraction
event, we will have an increase in
cytosolic calcium.
And the third is, is, is that we're going
to have a change in the membrane potential
or, or a change in the membrane in going
to be reflected by a change in the amount
of calcium within the cytosol.
And then the amount of calcium, then, in
turn is going to activate contraction.
So this is, again, going to be our E-C
Coupling.
Now, the smooth muscle itself is, is a
cylindrical cell.
It looks sort of like a cigar.
It's very narrow at one end, they have
tapered ends, and they're about 2 microns
in diameter.
And the center of the cell where the
nucleus is, is about 10 microns in
diameter.
In the light microscope, the cell does not
show the ai banding that we see in strided

muscle and instead the, the actin

filaments are a, attached directly to the
plasma membrane through what are called
dense bodies.
So these dense bodies are analogous to the
z lines that we see in strided muscle.
The actin actually is coming in at an
angle to the interior of the cell in so
that the actin on opposites sides of the
cell is not going to have, is going to
interact with myosin which is between
these, these filaments and draw the parts
of the cell in close together.
So that in the contracted state, we're
going to have a cell which is going to
change from a cigar or elongated shape, to
a cell that looks like a postage stamp.
And that's what's shown here.
The other thing that's unusual about these
sarcomeres that are of the smooth muscle,
is that we have no troponin.
Present within, on thin filament, so you
have no troponin-tropomyosin complex for
the regulation of those thin filaments by
calcium, and because the cells are very
small in diameter, we have no T tubules.
So the information then, when we dump the
calcium from the interior of the cell is
going to be by diffusion, we do not need
to have the T tubules.
Now, the smooth muscle is going to be
regulated, the contraction of the smooth
muscle is going to be regulated by myosin,
or the thick filament.
And if you recall, myosin is a molecule
that has a rod area and then the head.
And the head group actually is our ATPase.
So this myosin, this what I've just drawn,
drawn for you is the heavy chain of
myosin.
But there is also a light chain of myosin
which is a regulatory chain, which
regulates the head.
This light chain in smooth muscle becomes
phosphorulated when calcium rises within
the interior of the cell and the
phosphorulation event of the, of the light
chain.
Actually is going to activate the head
group of the, of the myosin, and allow
then the interaction between myosin and
actin.
So regulation of contraction is by
calcium, but that the regulation is going
to be on the thick filament, the myosin
filament, not on the thin filament as
we've seen in striated muscle.
The other part about this system is that
this is, this is a special kinase.
It's called the light the myosin light

chain kinase that adds this

phosphorylation group to this ATPase head.
The, the other thing about this is that
this is going to be a slow ATPase, so this
is a slow acting contraction.
This calcium itself is going to be
released from intracellular stores just
like we see in striated muscle.
And that is that it's going to come from
the endoplasmic reticulum or the
sarcoplasmic reticulum.
The endoplasmic reticulum is in smooth
muscle is the interior storage site for
the calcium, and on its surface it will
have ryanodine channels.
And these ryanodine channels won't open as
they do in skeletal muscle to arise in
calcium.
So we'll have a small amount of calcium
entering into the cell, and then that
amount of calcium will bind to the
ryanodine channel and cause a dump of
calcium, a very large amount of calcium,
to come out of the, the endoplasmic
reticulum and bathe all the contractual
elements.
To remove the calcium we have a calcium
ATPase on the, on the endoplasmic
reticulum, just as we have in skeletal
muscle.
But their smooth muscle can also cause a
release of calcium from
sarcoplasmic-reticulum by actually using a
second receptor and that receptor is the
Inositol trisphosphate.
And, so, that allows metabotropic
receptors on the cell surface.
To then activate a change in calcium,
intracellular calcium within the smooth
muscle cells, and we'll talk a little bit
about how this is actually occurs.
So again, it's the calcium where is going
to regulate our contraction and calcium is
going end and rise in calcium causes a
phosphorylation of the myosin light-chain.
And that activates the head group who
remove the calcium back into the
sarcoplasmic-reticulum.
We dephosphorylate that head and
contraction stops, and we have relaxation.
Now there are several different types of
contraction in smooth muscle.
Smooth muscle is able to contract at a
variable to variable states, so that we
can actually have what's called a tonic
contraction.
We can have a contraction where it's
completely contracted down as we see in
sphincters between for instance along the
GI tract, between the stomach and the

duodenum.
And here, here we have to relax the muscle
in order to allow materials to pass from
one compartment to another.
In addition to this, though, we also have
smooth muscle sitting around blood
vessels, and in the body this, they have a
certain tone, or certain toneness, that,
that's a basal state.
They can contract further down and
decrease the diameter of the blood vessel,
or they can relax and then allow the blood
vessel to increase in the lumen size to
increase.
This ability to have in a, sort of an
variable amount of contraction state is a
property of the tonic types of smooth
muscle.
The other type of muscle that we see, is a
phasic type of a contraction.
And that is, is that you stimulate the
smooth muscle, it contracts and then it
will relax when we remove calcium.
Smooth muscle also has a very variable
type of regulation and it can have both
positive and negative regulation.
So remember in striated muscle, skeletal
muscle.
Whenever we activated the neuromuscular
junction it was always, always excitatory.
In this case, the smooth muscle can either
be inhibited, because it's relaxed, or we
can cause it to contract.
And it's the net effect of all of these
different impinging factors on the smooth
muscle that dictates its actual contracted
state.
We have, in some smooth muscles we have
what are called mechanically gated
channels, and this is simply that these
are stretch channels.
So if we have on our blood vessel, we have
these this type of channel.
And if we increase the amount of blood
that's flowing through that vessel, we
will stretch the smooth muscle of the
walls and that will cause calcium to enter
through this mechanically gated channels
and cause a contraction.
We can also have ligand gated channels are
present on the smooth muscle and, as I
said, the autonomic nervous system
actually can control smooth muscle.
We have alpha one, adrenergic receptors,
which are going to cause contraction of
the smooth muscle, blood vessels, for
instance.
And we have beta 2 receptors which are
present on the smooth muscle's airways,
which cause the airways to dilate or cause

that smooth muscle to relax.

Smooth muscles also sensitive to hormones
such as oxytocin, when the mother is
delivering her baby, the oxytocin is
released into the system, and this hormone
actually causes stronger contractions of
the, of the uterine muscle, of the uterine
smooth muscle.
And finally we can have Paracrine agents.
Paracrine agents such as nitric oxide
which is a gas.
And the nitric oxide is released and it
will actually cause an increase in cycla
GMP within the cells.
And that actually is going to diminish the
amount of calcium, the amount of
phosphorylation on the myosin chain and
that we're going to get a relaxation
event.
And then lastly, we have the voltage gated
channels and the voltage gated channels
here are going to be voltage dependent
calcium channels.
Now, the smooth muscle also has a
pacemaker, some smooth muscles have a
pacemaker activity, and we've never talked
about that before.
What's known by its pacemaker activity is
that the resting membrane potential is
actually not stable.
So, for instance, here, we're starting
with a minus 55 millivolts, and this,
slowly, the resting membrane potential is
drifting towards threshold, which is at
minus 35 milivolts.
When the resting membrane potential
reaches minus 35 milivolts, it then will
trigger an action potential.
And we have the opening of the voltage
gated calcium channels to re-polarize the
cells we will open the voltage gated
potassium channels and that potassium then
will exit the cells and we will
re-polarize and as we re-polarize then we
come back to minus 55 milivolts the
resting membraine potential starts to
drift back toward threshold.
This is very periodic event and it has a
very set timing.and so it will occur
again, again, and again.
And this is called then the pacemaker
potentials.
Now, there are two kinds of smooth muscles
which are which we sort of put into two
different, two different classes.
These are called the single units smooth
muscles, single unit smooth muscles.
Single units smooth muscle, are connected
to one another through [inaudible], so
they're mechanically connected so when

they contract they pull on each other and

so the entire sheet sort, will pull
against each other.
And then they also have gap junctions and
this allows then for electrical for
electrical communication from cell to
cell.
And so that the contraction event for the
entire sheet is going to be synchronized.
These are the types of the smooth muscles
that we find in the walls of the GI Tract
in the uterus and around small blood
vessels.
The other type of smooth muscle are called
multi-unit smooth muscle and in this case
then, every single cell is actually
innervated so that, that because their not
electrically coupled, so we can have one
smooth muscle sitting next to another.
And it will contract, but its neighbor
will not.
These muscle cells are usually connected
to one another through [inaudible] zones.
So they're mechanically connected, but
they do not have this electrical coupling.
The cells that have this type of a, of a
personality are ones which are not going
to be sensitive to stretch activation.
And these, these are the smooth muscle
cells which are actually with the smooth
muscle cells which are involved with
raising your hair on the skin, which
whenever you get frightened or you're very
cold.
So what are our key concepts then?
So the key concepts are that smooth muscle
is involuntary, non striated muscle, and
it's associated with blood vessels and
with visceral organs.
The smooth muscle contains overlapping
proteins, myofilaments, which are actin
and myosin.
And that the relative sliding of the actin
past the myosin is what allows for
shortening our contraction and this is
what generates the force.
This process involves cross bridge
formation between the actin and the myosin
and it's driven by ATP and the ATPase is
located on the myosin head.
The third key, key concept is that we have
a coupling between the membrane action
potential and contraction.
And this is going to be mediated by a
change in intercellular calcium levels.
Calcium regulates myosin to enable the
cross bridge formation and the, and the
generation of tension.
The fourth, is, is that we have smooth
muscles is going be regulated by the

autonomic nervous system.

And that some smooth muscles also
regulated by stretch, and by hormones or
by paracine factors.
Five, we have the pacemaker cells, which
are a very special type of smooth muscle.
These action potentials are initiated by
an influx of extra-cellular calcium.
We have an unstable resting membrane
potential.
The cell's resting membrane potential
slowly rises his threshold and we open a
voltage gated calcium channel.
And then lastly, some smooth muscle will
exhibit fused tetanus.
These are the ones that have use of the
phasic muscles, where if we stimulate it,
it will contract.
But if we stimulate it again, and again,
and again, we can get summation of that
contraction, and we can get a fused
tetanus.
We also have some muscles which are called
tonic muscles, and these are the ones a
variable contracted state.
It can be highly contracted, such as we
see in the sphincters, or we can have a
variation in the contraction, such as you
see in the bladder for instance.
As you, as the bladder fills, the muscles
will stretch and eventually when it's
full, then the bladder will contact.
Alright, so next time when we come in
here, we're going to then talk about the
last form of muscle, and that's the
cardiac muscle.
See you then.