>>Dr. Ketchum: This is the third video lecture for neural integration, and in this video lecture we’re
going to be focusing on the voltage-gated channels. So in order to understand how a
neuron responds to its environment, you have to understand how voltage-gated channels can
change their configuration, and then ion permeabilities (through those open channels) can change the
membrane potential. But you need to understand the background behind or the fundamentals
of how these voltage-gated channels work. So in this outline, our focus is to look at
the types of channels in which we’ve already talked about leak channels, but we’re going
to be focusing on gated channels. And so then once we focus on our gated channels we'll spoke—
we will focus on specific types of gated channels as well.
So if you recall, I mentioned earlier that this particular slide you’d be seeing a lot
of this semester. And so we’ve already talked about our leak channels and the fact that
leak channels are always open. Now we’ve already talked about—in terms of gated channels—chemically
ligand-gated channels. So what you should do after we discuss voltage-gated channels
is you should compare and contrast what you learned about chemically gated or ligand-gated
channels to what you’re going to learn about voltage-gated channels. So the figure on the
right here illustrates voltage-gated channels for you. And so these voltage-gated channels
are going to open in response to a change in the membrane potential. So when the membrane
potential changes, a voltage-gated channel can open. Voltage-gated channels do undergo
conformational changes and voltage-gated channels do illustrate the concept of specificity,
which we’ve talked about on several occasions now. Please compare and contrast chemically
or ligand-gated channels to voltage-gated channels.
So we want to look at where these channels are located on the neuron or in the membrane
of the neuron, and various structures that make up the neuron. And so first off for leak
channels, leak channels once again are always open, and they’re located along the plasma
membrane of the entire neuron. So you would find leak channels in the plasma membrane
of the dendrites, the cell body, the axon, the axon terminal. The ligand-gated channels are going
to be found primarily on the cell body (we’ll use “cb” for cell body) and the dendrites.
And so you’ve already seen when you studied excitatory postsynaptic potentials and inhibitory
postsynaptic potentials, you’ve already studied these ligand-gated channels that are
located on the cell body and the dendrites. And so we also have sodium voltage-gated channels
and we have potassium voltage-gated channels. These are located at the axon hillock
and along the axon. There’s a higher concentration of these sodium voltage-gated channels and
potassium voltage-gated channels at the axon hillock. And the function for these channels
is to initiate and propagate the action potential. We have a third type of voltage-gated channels
and those are called calcium, calcium voltage-gated channels. These are located primarily at the
axon terminal. So when you study the synapse and events that occur at the synapse, you
will learn about voltage-gated channels and their activity at the synapse.
So first let’s focus on the voltage-gated sodium channels, and then we will return our
focus to the voltage-gated potassium channels. The voltage-gated sodium channels have two
gates. And that’s very important to remember. There are the inactivation gate and there
is the activation gate. It’s very important that you understand how each of these channels
works, or each of these gates rather, works. Both gates make up the voltage-gated sodium
channel. The inactivation gate on your figure looks like the ball and chain. So when it’s
closed, it’s bound to a receptor. And the inactivation gate responds to what the activation
gate does. So the voltage-gated sodium channel activation gate is voltage sensitive. Notice
we did not say the inactivation gate is voltage sensitive; it is not, it responds to what
the activation gate does. So if the activation gate is voltage sensitive, that means that
it will open in response in a change in a membrane potential.
So first off, let’s look at the configuration of the voltage-gated sodium channel when your
neuron is at rest. So remember the resting membrane potential for a neuron is negative
70 millivolts. In this particular situation, the activation gate is closed and the inactivation
gate is open. Remember we called the inactivation gate “the ball and chain,” so you can
see how it looks in this diagram. Remember that the inactivation gate has a receptor
that when it’s closed, it’s bound to that receptor. If the inactivation gate is going
to close, you have to activate the receptor in order for the inactivation gate to close.
So in this configuration, the activation gate is closed, the inactivation gate is open—we
call that configuration closed but capable of opening. What that means, and this is a
very important note, this means that your neuron is capable of responding to a stimulus.
So when your gates are in this configuration and you place you hand on the hot stove, your
neurons can sense the hot stove and you will remove your hand from the hot stove. So this
is the closed but capable of opening configuration. So the neuron will respond to a stimulus.
That’s the first configuration for the voltage-gated sodium channels.
The next configuration is the open or activated configuration. So here this is when the membrane
potential is from negative 50 or negative 55 millivolts to positive 30 millivolts. So
when the membrane potential is between negative 55 and positive 30 millivolts, we have an
open or activated voltage-gated sodium channels. So notice the configuration of the gates.
The activation gate is open, the inactivation gate is open, but the inactivation gate is
triggered. And what we mean by triggered is that it’s triggered to close. It is not
closed, but it is triggered to close. When the activation gate opens, that triggers the
inactivation gate to close. But it’s not closed, it takes a couple of milliseconds
for the inactivation gate to actually close. So in this case when both the acti—both the activation
and the inactivation gate is open, sodium can move into the cell. And when it moves into
the cell, it’s moving based on it’s electrochemical gradient. The last configuration for the voltage-gated
sodium channels is the closed and not capable of opening. In other words, the channel is
inactivated. When you think about this, think about the neuron and the fact that the neuron
cannot respond to a stimulus when the channels are in this configuration. So if you put your
hand on the hot stove and your voltage-gated sodium channels are in this configuration,
your neuron will not respond to that situation. Luckily for us it doesn’t happen, [laughs]
and we will explain that later.
Okay, so let’s look at what the gates are doing in this closed and not capable of opening
configuration. So here the activation gate is open and the inactivation is closed. Remember
that it was triggered to close when the activation gate opened. And now when it’s physically
closed, it’s bound to a receptor. So in this particular case, you have the inactivation
gate closed and any time you have any gate closed, your ion—such as sodium in this
case—cannot move through the channel. So you cannot have sodium influx when your chann—when
your gates are in this configuration. Now this configuration occurs when your membrane
potential goes from a positive 30 millivolts to a negative 70 millivolts. So we will be
using this information when we talk about the ionic basis for the action potential,
which will be the next video.
So we also have the voltage-gated potassium channels that are very important in an action
potential as well. And when you look at the voltage-gated potassium channels, you will
note that there is only a single gate. So we don’t have a particular name for the
gate, but there is only one gate. Voltage-gated potassium channels are slow. This inactivation
gate is also a tad bit slow. So it gets triggered, but even though it’s triggered, it doesn’t
close for a few milliseconds. So back to the voltage-gated potassium channel.
So we said that the voltage-gated potassium channel has one gate, therefore, it has
no name and it is slow. So when the voltage-gated potassium channel is closed, this is when
your membrane potential goes from negative 70 to positive 30. This is the point in time
where these voltage-gated potassium channels are closed. When the channel is closed, potassium
ions cannot move through the channel. So potassium ions cannot ent—cannot exit the cell.
When the voltage-gated potassium channel is open, which occurs when your membrane potential is—goes
from positive 30 to a negative 80 millivolts. When this channel is open, potassium can leave
the cell, or in other words we have potassium efflux, and what’s driving that efflux is
the electrochemical gradient. So for both potassium and for sodium, their movement is
based on electrochemical gradients. In this case potassium is leaving the cell, taking
its positive charge with it. Which is a very important concept that we will return to when
we discuss the ionic basis for the action potential, which will be the next video for
you to watch.