Action potentials in cardiac myocytes - Medical Video Lecture - MBBS

Let's figure out how a
heart squeezes, exactly.
And to do that, we have
to actually get down
to the cellular level.
We have to think about
the heart muscle cells.
So we call them
cardiac myocytes.
These are the cells
within the heart muscle.
And these are the cells that
actually do that squeezing.
So if you actually were
to go with a microscope
and look down at
one of these cells,
it might look a
little bit like this,
with proteins inside of it.
And when it's relaxed, these
proteins are all kind of spread
apart.
And when it's squeezing
down, because each cell has
to squeeze for the
overall heart to squeeze,
these proteins look
completely different.
They're totally overlapped.
And that overlapping is
really what we call squeezing.
So this is a squeezed
version of the cell.
And the first one was
a relaxed version.
And the trigger that kind
of gets it from squeezing--
and of course actually, I
should probably draw that too.
The fact that, of course, at
some point it has to go back to
relaxed to do it
again, to beat again.
But the trigger for
squeezing is calcium.
So it's easy to get confused
when you're thinking about all
this kind of squeezing relaxing
all this kind of stuff.
But if you just keep
your eye on calcium
and think about the fact
that calcium is the trigger,
then you'll never get confused.
You'll always be
able to kind of find
your way in terms of where
the heart is in its cycle.
So I'm going to draw for you the
heart cycle, and specifically
the cycle of an individual cell.
This is what one cell is
going to kind of go through
over time.
And the heart cycle, or the
cycle for a cell, a heart cell,
is going to be
measured in millivolts.
We're going to use millivolts
to think about this.
And you could use, I guess,
a lot of different things.
But this is probably one
of the simplest things
to kind of summarize
what's happening
with all of the
different ions that
are moving back and
forth across that cell.
Now the major
ions, the ones that
are going to mostly
influence our heart cell,
are going to be calcium,
sodium, and potassium.
So I'll put those three on here.
And I'm putting them
really just as benchmarks
just so you can
kind of keep track
of where things
would like to be.
So calcium would like
to be at 123 millivolts.
Sodium at 67.
And what that means is that if
these were the only ions moving
through, then sodium would
like to keep things positive.
And potassium, on
the other hand,
would like to make the
membrane potential negative.
So this scale is
actually the scale
for the membrane potential.
And if we move up
the scale, if we
go from negative to
something positive,
this process would be
called depolarization.
That just means going
from some negative number
up towards something positive.
And if you were
to do the reverse,
if you were going to from
something positive to something
negative, you'd call
that repolarization.
So these are just a couple of
terms I wanted to make sure
that we're familiar
with, because we're
going to be able
to then get at some
of the interesting
things that happen.
I'm going to make some space
here inside of this cell.
So let's start with a
little picture of the cell.
So let's say that
this is our cell here.
And I'm going to draw in
little gap junctions, which
are little connections
between cells.
So maybe a couple there.
Maybe one there and
maybe one over here.
And let me label that.
So these are the gap junctions.
And also let's draw
in some channels.
So we have, let's say, a
potassium channel right here.
We know the potassium
likes to leave cells.
So this is going to be the way
that potassium's going to flow.
And it's going to leave behind
a negative membrane potential,
right?
And let's say potassium
is the main ion
for this cell, which it is.
Then our membrane
potential is going
to be really, really negative.
In fact, if it was the only
ion, it would be negative 92.
But it's not.
It's actually just
the dominant ion.
So it's over here and
our membrane potential
is around negative 90.
And it continues
around negative 90.
So let's say nothing
changes over a bit of time.
So we stay at negative 90.
So this is what things look
like with the dominant ion
that our cell is permeable
to being potassium.
Now a neighboring
cell, let's say now,
has a little bit of
a depolarization.
So it goes positive
and through the gap
junctions leak a little bit
of sodium and some calcium.
So this stuff starts leaking
through the gap junctions,
right?
Now what will happened to
our membrane potential?
Well it was negative
90, but now that we've
got some positive ions
sitting inside of our cell,
our cell becomes a little
bit more positive, right?
So it goes up to,
let's say, here.
And it happens pretty quickly.
So now it's at negative
70 up from negative 90.
So at this point,
you actually get--
I'm going to erase
gap functions--
but now that you're
at negative 70,
you actually get new
channels opening up.
And I haven't drawn
them yet, and I'm
going to erase sodium
and calcium just
to make some space.
But you get new
channels opening up.
And these are going to
be the sodium channels.
So let me draw those in.
Sodium channels.
And there's so many of them.
Lots and lots of these fast
sodium channels open up.
And I say fast
because the sodium
can flow through very quickly.
So the sodium starts gushing in.
And you know that's going
to happen because there's
a lot more sodium on
the outside of a cell
than the inside of a cell.
And so sodium
gushes in, and it's
going to drive the membrane
potential very quickly up
to a very positive range.
Now it would go all
the way, let's say
close to 67, maybe
not exactly 67,
because you still have those
potassium ions leaving.
But close to it,
if not for the fact
that these voltage-gated
channels actually close down.
So these sodium channels
are voltage-gated.
And they will actually
close down just as quickly
as they opened up.
To show that, I'm actually
going to do a little cut paste.
I'm going to just
draw this cell here.
And I'm going to
move it down here.
So we've got our
cell just as before.
And now these voltage-gated
channels, they close down.
So let me get rid of
all these arrow heads.
But we're already now
in positive range.
So at this point, you
could say our channels
have caused a depolarization.
And let me just quickly
show these shut downs
so that you don't get confused.
There's no more sodium
flowing through.
You still have some
potassium leaking out,
but that's kind of
as it's always been.
And in addition to those
potassium channels,
that little channel
I've drawn here,
you have new potassium channels
that open up down here.
And these are actually
voltage-gated potassium
channels.
So you had them before.
They existed.
But they were actually not open.
So let me just draw little x's.
And the only reason
they flipped open
is because the
depolarization happened.
You had a negative
go to a positive.
So now that our cell is
in positive territory,
actually let me write
in positive 20 or so,
our potassium voltage-gated
channels open up.
So these voltage-gated
channels open up.
And you can guess
what's going to happen.
Like which direction
do you think
that the membrane
potential will go?
Well, if the sodium channels
aren't gushing the sodium
inwards and potassium
is leaking outwards,
now you're going to have a
downwards repolarization.
So now potassium is causing
the membrane potential
to go back down.
And let's say it gets
to about positive 5.
And if it continued, again, it
would go all the way back down
to negative 90.
But an interesting new
development occurs.
At this point, I'm going to
actually cut paste again.
And I'll show you what happens
next, which is that calcium--
this is the thing I said keep
your eye on the whole time,
right?-- calcium finally
kind of starts leaking in.
So let me get rid of this.
And this is the key idea, right?
I don't want to forget
that this is potassium.
So you still have potassium
in the same over here.
But now calcium leaks in.
And let's draw that over here.
So you have these calcium
voltage-gated channel
that allow calcium to come it.
So you've got calcium coming
in, potassium leaving.
Now think about what will
happen in this situation.
So calcium is going
to want to rise
the membrane potential this way.
Potassium leaving
is going to want
it to continue
going down this way.
And because both are
happening simultaneously,
you basically get
something like this.
You get kind of a flatline.
So because both
events are happening,
both potassium leaving the cell
and calcium entering the cell,
you get this kind of flatline.
And the membrane potential
stays kind of around the same.
And so it can just
write something similar,
something like positive 5.
Just so we're clear,
these are also
voltage-gated calcium channels.
So to round this out, then
what happens after that?
So you have so far, so good.
We have all these channels
coming in to our cells
and allowing different
ions passage.
And now we get to
something like this.
And I'm going to try to
clean this up a little bit.
And what happens is that the
calcium channels actually
close just as suddenly
as they opened.
So now you don't have any
more calcium coming in.
And if calcium was
the only thing that
was keeping this
membrane potential going
flat-- you know, I said
that the potassium makes
it want to go down,
but the calcium
was making it flat-- well,
what will happen now?
Well, if again you have just
those potassium channels open,
well then you're going to
have the membrane potential go
back down.
It's going to go back
down to negative 90 or so.
So this is kind of the last
stage, where those potassium
channels are going back down.
And those voltage-gated
potassium channels
also close at this point.
So finally, they
close down as well.
And so now that
they're closed, you're
going to finally get back to
just your initial state, which
was having a little bit of
potassium kind of leaking out
of this cell.
And those voltage-gated
channel have shut down now.
So now that you're at negative
90, you stay down there.
And this process is
ready to begin again.
The last thing I want to say is
the stages, how they're named.
So this is state four, this
kind of baseline negative state
that the relaxed muscle cell is.
And then this action potential,
when it finally fires
and it hits that
negative 70, this
is actually considered
a threshold.
This is our threshold.
When it gets to that point,
we call that stage 0.
And then on the
other side of stage 0
you have stage 1, 2, and 3.
So stage 1 is that point
when just the potassium
channels first open up,
the voltage-gated ones.
And then stage 2 is when they're
balanced with the calcium
channels.
And stage 3 is again when you
have just potassium channels,
voltage-gated ones
that are open.
And then you get back
to stage 4 again.
So this would be stage 4.
And because stage 0 is happening
so rapidly, because this
is so fast, we actually call
this a fast action potential.
So compare that to how
the action potential goes
in the pacemaker cells,
where it's much slower.
This fast action potential
is a result of those really,
really amazingly quick
voltage-gated sodium channels.