>>Dr. Ketchum: So we have been learning about pacemaker cells and how pacemaker cells are
located in the conduction fibers within the conduction system, and we keep mentioning
that these pacemaker cells generate action potentials. And so what we would like to do
now is look at this pacemaker activity. When you look at this graph, there’s some important
terminology for you to understand. We use the term “pacemaker potential” loosely
at times. The pacemaker potential is actually just the graded potential of the pacemaker
activity. Numbers one and two here technically are called the pacemaker potential.
However, it’s very common for researchers and, and physiologists to call the entire graph a pacemaker
potential. And so I try my best to only talk about the pacemaker potential in terms of
this graded potential, however, that doesn’t always happen. And so since it’s a, a common
occurrence amongst physiologists, if I say pacemaker potential, it may—this may include
the entire action potential as well. When these pacemaker cells generate these action
potentials, remember that they’re traveling through the conduction system. And when they
travel through the conduction system, they can also travel to cardiac contractile cells.
And they can travel to those cardiac contractile cells via what structure? Gap junctions. Okay,
so let’s take a look at this pacemaker activity. So first off, the first thing to note is that
the resting the membrane potential is somewhere between negative 60 millivolts and negative
70 millivolts. So the resting membrane potential we say is unstable, and the reason we say
it’s unstable is that the cell does not stay at rest for very long. It’s a very
short term that the cell is actually at rest. So let’s look at the phases of the pacemaker.
I started you off with phase four, which is repolarization. So the number on your slide
is the same number indicated on the graph. So step four here is repolarization, something
that you’re very familiar with. Steps one and two are part of the pacemaker potential.
They are the graded potential. Number one is the first part of slow depol, and number
two is the second part of what we call slow depolarization. So when we talk about slow
depolarization that is strictly includes only one—numbers one and two on the graph. Number
three on your graph is what we call rapid depolarization. Let’s look at threshold.
We’ve talked about threshold in a neuron before, but now we’re talking about threshold
in a cardiac cell. Threshold in the cardiac cell—in a pacemaker cell, specifically—threshold
is at negative 50 millivolts. So everything we’re referring to here is happening inside
of a pacemaker cell. So what I’d like to do now is go through each of the phases of
a pacemaker and look at what channels and what ions are moving, and therefore causing
these various phases.
We’ll start with repolarization. In repolarization, just like in a normal neuron, the voltage-gated
potassium channels are doing what? Hopefully you said they’re open. Remember at the peak
they’re open, and as you go through repol, more and more of them are open. So through
the open voltage-gated potassium channels, which way does potassium move? Do we have
potassium influx or potassium efflux? Hopefully you said that we have potassium efflux. Remember
that potassium is moving along its electrochemical gradient, so it’s—and it’s moving out
of the cell. Keep in mind that the equilibrium potential for potassium in this pacemaker
cell is the same as if it was a neuron, so negative 90 or negative 94 millivolts. So
also during repolarization we have a new type of channel to briefly introduce you to, and
I’ll talk more about it in a few moments. In repolarization, the voltage-gated L-type
calcium channels are closing. I’ll return to those L-type calcium channels shortly.
After repolarization and the cell reaches rest—and remember, it doesn’t stay at
rest for very long—and the reason it doesn’t stay at rest for very long is because of a
new type of channel called a sodium funny channel. And I didn’t make that name up.
It’s true; it’s called a funny channel. And the reason physiologists named it a funny
channel is because it behaves differently. It doesn’t behave like a voltage-gated channel
in the sense that it doesn’t open in response to a change in the membrane potential. Instead,
it responds to repolarization. And so when I say it responds to repolarization, what
I mean is it’s going to open. So it’s opening during this first part of slow depolarization.
When it opens, it’s only open for a brief moment in time. So it opens and closes, opens
and closes, opens and closes, very quick open and closed. So when it is open, which way
does sodium move? Do we have sodium influx or do we have sodium efflux? This is like
a regular neuron, and so you will have sodium influx. So sodium is moving along its electrochemical
gradient. But again, it’s very important to realize that when this funny channel opens,
it closes. Open and closes very quickly. When you look at phase one on the graph, look at
how short it is, and the reason it’s so short is because of that channel opening and
closing. Now while this is happening, your voltage-gated potassium channels are closing.
So now let’s continue on with our slow depolarization. We’re do—we have finished the first part
of slow depol. When we have sodium influx, did that change the membrane potential? The
membrane potential became a little more positive, correct? So because we had a change in the
membrane potential, and this change in the membrane potential triggers a voltage-gated
T-type calcium channel to open. Now the “T” stands for transient. So what this means is
this is kind of like the sodium funny channel where this channel opens and closes, opens,
closes, opens and closes. So again, look at phase two on your graph and look at how short
this part—the second part of slow depol is. Because the membrane potential is becoming
more positive when the T-type calcium channels are open, do we have calcium influx or calcium
efflux? Remember that calcium is going to be moving along it’s electrochemical
gradient as well, and that direction is into the cell, or calcium influx. Remember that
the equilibrium potential calcium is positive 130 millivolts. That will be important.
The voltage-gated T-type calcium channels, when they open and then they close,
this is enough to get the membrane potential to threshold. So at negative 50 millivolts,
we are at threshold. And now—because we’ve had a change in the membrane potential again—another
voltage-gated channel is going to open, and this one is called the voltage-gated L-type
calcium channel. “L” stands for long lasting, meaning that it’s open for a much longer
period of time than the T-type calcium channels are. So this voltage gated L-type calcium
channel, when it opens at negative 50 millivolts, you have calcium influx. And so positive charges
moving into the cell, and that’s what creates the rapid depolarization phase of the pacemaker.
Once the peak is reached of this action potential, then the L-type calcium channels begin to
close, the voltage-gated potassium channels are open and you have potassium efflux,
and hence, the membrane potential becomes more negative. And so it’s very important
for you to be able to draw a pacemaker—both a pacemaker potential and the pacemaker action
potential—to be able to draw it, because there are lot of scenarios and, and things
that could go wrong with the various channels.