Sympathetic nerves affect myosin activity - Circulatory System Video Lecture - MBBS

We're going to do a
little comparison.
I'm going to draw three
different people here--
or it could be
the same person, I
suppose-- in three
different situations.
So you've got the first
person just kind of sitting
and maybe they're watching a
YouTube video on their laptop.
And you've got a
second person who's
actually going
for a little walk.
Let's see if I can draw
this person walking.
And you've got a third person
who's-- let's say this person
is actually really active
and they are running.
So they are actually in
full stride, running.
And maybe they're late
for a test or something.
So-- oh, let me actually change
that so their arm does not
look broken.
So there have
these three people.
And they're running and
walking and sitting, right?
So you can imagine if you were
to take a look at their heart
cells they might be
doing different things.
In fact, let's draw
all three's heart cells
and show you what
they might be doing.
So we've got our heart cell.
And in this case I'm actually
going to draw also a nerve.
This is going to be
the sympathetic nerve.
I'll write an s, for
sympathetic nerve.
And the heart cell,
just to be clear,
is going to be a
ventricular heart cell.
So this is a-- I'll write
ventricular heart cell here.
Just so that we know we're not
talking about some pacemaker
cell or some other
cell in the heart.
This is a ventricular cell.
And now, just to remind us
of a couple things we know,
this ventricle cell is branched.
And it's got two little nuclei.
And it's got some receptors
on its surface waiting
for, potentially, norepinephrine
from that sympathetic nerve.
Right?
Now inside of that
heart cell, if we
were to dive inside of the heart
cell, you might see some actin.
And you'd see that at
the ends of the actin.
It's a Z-disk, right?
So we've got a Z-disk
with our actin.
And I've drawn this
far too close together.
Let me actually make a
little bit of space in here.
But you get the idea.
You've got our actin kind
of like little ropes.
And in the middle
you've got our myosin.
And our myosin, you
remember, is basically
going to have a whole
bunch of myosin heads.
And these heads are
going to want to do work.
They're going to want
to pull the actin
and yank that Z-disk closer
to the middle, right?
That's what they want to do.
So these myosins are hanging
here, waiting to do work.
And their trigger
for work, of course,
is going to be calcium
binding the troponin C
and pulling tropomyosin
out of the way.
So this is our actin and myosin.
This is our actin up here.
And we've got our
myosin in the middle.
And then finally, I'll
draw one last thing
and that is the titan.
And the titan,
remember, is a protein
that basically is
going to attach
the myosin to the Z-disk.
Remember, our Z-disk is
this thing at the end.
This is our Z-disk over here.
Let me just kind of
draw it in for us.
This right here is our Z-disk.
I've been calling it a Z-disk.
Sometimes you see Z-line.
That's kind of interchangeable.
But this is our
Z-disk right here.
And it's basically tethered
by those actin ropes,
you can think of them as.
And we're going
to use those ropes
to pull the Z-disks together.
So this is basically the set
up and what it looks like.
And now I'm actually going
to just take this and cut
and paste it a couple of
times so that we can actually
use this for our two
other situations.
We've got one there.
And we can actually do it
again and have it like so.
So now you can see our
three situations side
by side and our three setups
with our actin, myosin,
and our Z-disks.
So what would happen
in situation one?
Well in situation one
you're just hanging out.
You're happy.
You're maybe watching something
kind of funny on YouTube.
And you don't have
much sympathetic drive.
You don't have any
stimulation coming
from your sympathetic nerves.
You're not running or you're
not frightened, let's say.
So you have-- you know, your
normal amount of calcium
comes into the cell when
it's time to contract.
And so you get a little
bit of calcium in here.
Looking over at the other side,
when the calcium comes in,
you have a low amount
of calcium, let's say.
Because not much is coming
through the channel.
You're not activating
that channel in any way.
So that calcium, let's say, it
binds here and it binds here.
And let's say a little
calcium binds here and here.
And when I say binds
remember I mean
it binds the troponin
C. Remember that.
So the calcium binds there.
And what do you get?
Well let's draw a little table
on the side of-- this is,
let's say, the
proportion-- I'm trying
to make sure I
phrase it correctly--
the proportion of myosin
heads that are working.
And if you count them
up, if you count up
all the little purple heads--
you can do that right now--
you'll see there are 20.
So this is the proportion of
myosin heads that are working.
And what would you get
for this first situation?
Well, at four spots the
calcium has bound, right?
And it doesn't bind forever.
At some point the
calcium is going
to be kind of taken back into
the sarcoplasmic reticulum,
or thrown out of the cell.
But for the time that
our heart is contracting,
for that brief bit of time, how
many myosin heads are working?
Well we've got
this guy over here.
This guy.
And we've got this
guy down here.
And we've got this
guy and this guy.
So four of them are working.
And that means that
16 are not working.
So 4 out of 20 are working.
So really we've got-- what
does that work out to?
20%.
That's equal to 20%
of them are working.
So that's not too many.
But what's going to happen?
Basically these
myosin heads are going
to pull-- let me erase
the little arrows,
not to confuse you.
But basically
these myosin heads,
these four that are
working, are going
to pull the actin
that way and that way.
And this way and this way.
And the Z-disks will
come closer together.
Let's not be confused
about that point.
The Z-disks definitely
will come together.
But it's going to take a while.
Really it's like
having four-- you
can think of it as four of
your friends pulling on a rope.
It's not as effective
as having 20, right?
So let's go to
situation number two.
So in situation
number two, let's say
now you're going for a walk.
And you're enjoying
the beautiful day.
But you're walking, right?
And so there's a
little bit of activity.
And so let's say your
sympathetics are firing
a little bit, a little bit
of a sympathetic drive here.
And a little bit of
neurotransmitter gets released.
And so this neurotransmitter, we
know, is called norepinephrine.
And so a little
bit gets released
into that space
between the nerve
and the cell, the heart cell.
And it binds to, let's
say, one of the receptors.
So one of the receptors
is going to fire.
And during a muscle contraction
you've got calcium coming in.
But because that
receptor fired now
you have a little bit
extra calcium coming in.
Meaning that channel
has been activated
so that it's letting
more calcium in.
OK so if more calcium's coming
in-- let's now take a look
at our diagram.
Now you've got a little bit more
calcium coming in and binding.
And I'm just choosing them
by random, in a sense.
But let's say these six.
And on this side let's
just choose another six.
Let's say four up here and
maybe a couple down here
are going to bind calcium.
So you've got troponin C's
that are binding calcium.
And of course that
means that those
are the myosin heads
that get to work.
And so in total, how many
myosin heads are working?
Well now instead
of only four total,
we've got-- what is
that-- 12 myosin heads out
of 20 working, or 60%.
So it's really gone
up considerably.
So just as before,
you're going to have
the Z-disks getting yanked in.
But now the yanking is
going to be much more
forceful because you've got
many more myosin heads actually
involved in dragging
that Z-disk over.
So this is actually
quite interesting
because now you can
see that you have,
as a result of the
sympathetic drive, more force
in your contraction,
your heart contraction.
So you can probably guess where
the last one is going to go.
Now you're running.
You're excited.
And let's say, now instead
of just a little bit
of transmitter, you've got
tons of neurotransmitter being
released, lots and
lots of norepinephrine.
In fact, let's say a
little bit over here.
And you've got all three
receptors kind of firing,
right?
Because all that
norepinephrine is
allowing lots and lots of
stimulation to the cell.
And so with all
this norepinephrine
your calcium channels are going
to be really active, right?
They're going to be
pouring in calcium.
So instead of just a
little bit of calcium,
now when you have a
contraction you've
got lots of calcium dumping
into the cell, right?
And this is, of course,
just during the time
when your contracting
or squeezing.
So with all this
calcium now it's
going to go and bind the
troponin C everywhere
it can find the troponin C.
It's going to come and sit
basically everywhere.
And all these myosin
heads are excited
because now they
all get to work.
And with this full set
of myosin heads working--
you have 20 out of 20 working.
You have 100% of
them doing their job.
And as a result you
can see that now you're
going to have a huge mechanical
force, enormous forces,
yanking those Z-disks
closer together.
So in all three
situations you do
get the Z-disks coming together.
But remember, the period
of time that the calcium is
in the heart is finite.
Right?
It's not like it's
there forever.
Because, at some point,
that calcium's going to get,
as we said, brought
back out of the cell
or into the
sarcoplasmic reticulum.
So while it's there, for
those few precious moments
that the calcium is
there, you really
want your heart to be able to
do as much work as possible.
And in this case,
you're actually
seeing that here at the
top-- let's actually
draw an arrow-- at the top this
side there's really low energy
use because not too
many of the myosin heads
are actually converting
ATP to ADP plus phosphate.
So remember, the myosin
heads that are working--
those are the only ones that
are actually converting ATP
to ADP plus phosphate.
And the ones that
are not working
are of course not doing that.
So in this case you can also
see that, in addition to force,
the other thing that's less
in this sitting situation
is that it's a low-energy state.
You're not really
burning any energy.
Whereas over here,
when you're running,
each one of these myosin
heads is cranking through ATP.
It's making lots
and lots of ADP.
So it's using lots of energy.
It's a high-energy situation.
In other words, you're using
up a lot of energy here.
And so of course
this makes sense.
Right?
Because you think, well if
I go for a run of course
I'm going to use up energy.
Whereas if I'm just sitting I'm
not using much energy at all.
And now you can see exactly
why that's the case.
Because in the running
situation, all 20
of your myosin heads
are burning through ATP.