>>Dr. Ketchum: This will be the part two of two lecture notes for the ionic basis of action
potentials. And so we are going to begin with the rapid depolarization phase of the action
potential. So here we are assuming that threshold has been reached. Again, we had an excitatory
postsynaptic potential, which brought the membrane potential to negative 55 millivolts,
which generated an action potential at the axon hillock. So in rapid depolarization,
this is number three. And in rapid depolarization your membrane potential is going to be changing
from negative 55 millivolts toward positive 30 millivolts. But what we—what we want
to know is why, right? In physiology we always ask why. So we want to look at how does that
membrane potential become more positive? Well that’s going to be dealing with the configuration
of your voltage-gated ion channels. So let’s look at the voltage-gated sodium activation
gate. So as you can see here, the activation gate now is open. So at negative 55 millivolts,
these voltage-gated sodium activation gates begin to open. And so they don’t all open
at once along the length of the axon, but they open in a progressive fashion. So one
channel opens and the next channel opens, and the next channel opens, and so on. Now
the voltage-gated inactivation gates are open. However, when the activation gate opens, that
is going to trigger the receptor for the inactivation gate. And when you trigger the receptor for
the inactivation gate, that tells the inactivation gate to close. It is only triggered; that’s
important. Meaning it’s still open, but it’s been triggered to close. Remember that
the inactivation gate is slow. Now, the other thing that happens is that the voltage-gated
potassium channels—yes, when you look at the diagram they are closed. However, voltage-gated
channels are always stimulated to open when there’s a change in the membrane potential.
So we’ve had a change in the membrane potential to negative 55 millivolts. So yes, that will
stimulate voltage-gated potassium channels to open; however, they are only triggered.
Remember they are slow, so they are not open at this point. They are slow to open. So they’re
closed, but they’re slowly opening, but they’re never actually open during this
phase in the action potential. When we look at the configuration of these channels and
potassium channels are closed, voltage-gated sodium channels are open, you can look at
sodium and how sodium is going to be moving into the cell along it’s electrochemical
gradient. So if we have positive charges moving into the cell, that will force your membrane
potential to become more positive or less negative. So that’s what’s calling—causing
the depolarization is a sodium influx into the cell.
So let’s look at why this depolarization is called rapid depole. Let’s put in some
voltage-gated sodium channels. With these voltage-gated sodium channels, and we’re
at the axon hillock and the membrane potential has reached negative 55 millivolts. So that
means the activation gate is going to open. And when the activation gate opens, sodium
can move into the cell carrying a positive charge. Now, did that change the membrane
potential at that part of your neuron? Hopefully you answered yes. And because it changed the
membrane potential there, that stimulates the next voltage-gated channel to open and
sodium will move into the cell, bringing more positive charges with it. And then that change
in the membrane potential will stimulate the next voltage-gated channel to open, and therefore
sodium comes into the cell once again. So we’ve entered into a, a type of feedback
that you should probably be familiar with, and we’re enhancing a change. So this is
called positive feedback. And so positive feedback is the reason that the slope of rapid
depolarization is so steep. So the next phase of your action potential
then is called repolarization. And in repolarization, this begins at the peak. So it begins here
at number four, and then it continues until the membrane potential reaches negative 70
millivolts. So repol then goes from positive 30 (when your membrane potential goes from
positive 30 millivolts) back down to negative 70 millivolts. So let’s look at what’s
causing this, what’s responsible for this. So by the time you reach positive 30 millivolts,
the sodium inactivation gate, remember it was triggered to close in depol? Well, now
it’s closed. It was so slow that it took it all to get to repol before it closed. The
activation gate is still open, but if the activation gate is open and the inactivation
gate is closed, as you see in your diagram, can sodium move into the cell? No. You can
have no sodium influx at this point because one of the gates is closed. Now remember the
voltage-gated potassium channels were triggered to open during depolarization, but they’re
so slow that they don’t actually open until repol. And so please realize that this is
a dynamic process: When the peak of your action potential here is reached, that does not imply
that all of your activation gates are open and all of your inactivation close all at
once. It’s dynamic, it moves down the length of the axon. And the same is true for the
voltage-gated potassium channels. They do not all pop open at once; it occurs progressively
down the length of the axon. Let’s take a look at the configuration of your voltage-gated
sodium channels. Here we have the voltage-gated action gate is open; the inactivation gate
is closed. This is the closed and incapable of opening configuration. In other words,
what this means is that these gates have been inactivated. So if we close the inactivation
gate, in other words, this neuron cannot respond to another stimulation. These gates, rather,
are closed and they're incapable of opening, so they cannot respond to another stimulus. What refractory
period would this be? I’ll leave that an open-ended question for you to figure out.
Now the next phase of the action potential then is hyperpolarization. So in hyperpolarization,
your membrane potential is going to become more negative than rest. So hyperpolarization
occurs when the membrane potential goes from negative 70 millivolts down to about negative 80 or
negative 85 millivolts. So again, let’s look at what’s causing hyperpolarization.
At this point in time, your voltage-gated activation gates are now closed. And again
it’s dynamic, so they don’t all close right at the beginning of hyperpol, but throughout
hyperpolarization they close. The voltage-gated sodium and activation gates, they close temporarily.
Remember we said that the inactivation gates respond to whatever the activation gate
does? So if the activation gate closes, the inactivation gate is going to be closed, but
then it will pop open. So there’s only a split second there where both of those gates
were actually closed. The voltage-gated potassium channels begin to close at negative 70, and
remember, they are slow to close. So if they’re starting to close at negative 70 but yet they’re
really slow to close, can you still have potassium efflux occurring? Remember we had potassium
efflux occurring during repolarization, and that’s why the membrane became more negative
in repol. So potassium here is still exiting the cell because the potassium channels are
slow to close. You still have some potassium efflux, and that’s what’s causing the
membrane potential to become more negative than rest. Eventually, those voltage-gated
potassium channels will be closed. And by the time you reach about negative 80 millivolts
or negative 85 millivolts, they are actually closed by that point in time.
Now, let’s once again look at the configuration of your voltage-gated sodium channels.
So during hyperpolarization or near hyperpolarization, your voltage-gated sodium channels—the activation
gate is closed and the inactivation gate is open. And so here remember that this is the
closed but capable of opening configuration. And the reason it’s capable of opening is
because the voltage-gated activation gate is the one that responds to a change in the
membrane potential. So if a new stimulus comes along and that gate’s closed, it will respond
to a change in the membrane potential. If the gate’s already open, it cannot respond
to a change in the membrane potential. So in this case—in this configuration where
the gates are closed but capable of opening—you’re in another type of refractory period, and
I’m just gong to leave it up to you to decide which refractory period that this is.
So now hyperpolarization is over, and we’re going to assume that there’s no new stimulus.
So remember, during depolarization you add sodium influx. So sodium ions enter the neuron,
causing the neuron to become more positive, and that’s why depolarization occurred.
During repolarization, we had potassium efflux. So positive charges leaving the neuron and
therefore causing the neuron to become more negative or the membrane potential to become
more negative. So now we need to restore our ion distributions. One thing that’s really
important to understand is that yes, there were ions moving during the action potential,
however, there’s very little ion movement actually taking place. So we can restore the
ion distributions using the sodium potassium pump and the leak channels, they can work together
to restore the ion distributions. So my question for you is does this event have to be completed
before the neuron can be stimulated again? In other words, do you have to restore the
ion distribution before that neuron can respond again? I’ll give you a little hint: Think
about the configuration of the voltage-gated sodium channels. Okay, so now the cell is
returned to rest, and it’s returned to rest by using a sodium potassium pump and the leak
channels as well. So we’ve restored your ion distributions, your voltage-gated activation
gate for sodium is closed. Your inactivation gate is open; your voltage-gated potassium
channels are closed. And that’s the end of the action potential for this neuron. So
this neuron has responded to some stimulus, and now the stimulus is gone, so it has stopped
responding. So that is the end of this segment. Thank you for listening.