>>Dr. Ketchum: In this segment of the neural integration notes, you’ll be learning about
inhibitory postsynaptic potentials. Here’s the same outline that you saw in the excitatory
postsynaptic potential lecture, and in this segment we will only be focusing on the inhibitory
postsynaptic potentials. This is also the same overview that you saw on the excitatory
postsynaptic potential lecture. Be sure you understand what channel-linked receptors are
and G-protein linked receptors are before proceeding. And remember, when we talk about
postsynaptic potentials, we’re talking about types of graded potentials. And so we’ve
already discussed our excitatory postsynaptic potentials—our EPSPs. And in this segment
we’re going to be focusing on our inhibitory postsynaptic potentials.
Now just to review quickly, the excitatory postsynaptic potentials bring the membrane
potential of the postsynaptic membrane closer to threshold. And the closer you are to threshold
or negative 55 millivolts that increases your chances of generating an action potential
on the postsynaptic membrane. So remember if threshold is reached, an action potential
will occur. So let’s compare this to an inhibitory postsynaptic potential. In an inhibitory
postsynaptic potential, we want to bring the membrane potential of the postsynaptic membrane
further from threshold. We want to take it away from threshold in a negative direction.
So we can do that in an inhibitory postsynaptic potential or we can stabilize the membrane
at negative 70 millivolts, which if you recall, would be at rest—
stabilizing the membrane at rest. Either way, if we bring the membrane potential further
away from threshold or we stabilize the membrane potential at negative 70, both of these are
going to decrease our chances of generating an action potential on the postsynaptic neuron.
They’re decreasing the likelihood because now our membrane potential is further away
from threshold, and the further away from threshold you are, the less likely you are
to generate an action potential. So inhibitory postsynaptic potentials can occur by opening
either fast potassium channels or fast chloride ion channels.
So once again, whenever we begin, think about what’s the goal—what’s the big picture
for these fast inhibitory postsynaptic potentials? In this case, since we’re dealing with potassium
channels, the goal is to hyperpolarize the postsynaptic membrane. If you hyperpolarize
the postsynaptic potential membrane, it is more negative than rest (which remember is
negative 70 millivolts.) So we’re moving that membrane potential further or more negative
than negative 70 millivolts. So let’s look at how this can happen.
And so we’ll start with number one. And you have a neurotransmitter that binds to
the receptor. Now remember this is a fast IPSP, so that receptor must be called an ionotropic
receptor. So once that occurs and the neurotransmitter binds to the ionotropic receptor, the potassium
channel opens. And when the potassium channel opens remember that we have a potassium gradient,
and there’s a higher concentration of potassium in the cytosol of your cell and a lower concentration
of potassium in the extracellular fluid. So potassium is going to move out of the cell.
So we will have potassium efflux. And so one thing to think about is, well, potassium carries
a positive charge and it’s taking its positive charge with it outside of the cell. So because
the cell is losing positive charges, this is going to cause the membrane potential to
become more negative than rest. So what this means then is that we hyperpolarize the membrane.
And once we hyperpolarize the membrane, this decreases our chances of generating an action
potential. That’s why it’s called an inhibitory postsynaptic potential; we’re decreasing
the chances of generating an action potential on that postsynaptic membrane.
Now we can also generate inhibitory postsynaptic potentials by using chloride channels, and
there are three different ways in which this can be done. I’m going to step you through
each one of these, realizing that these mechanisms would be found on different neurons. So let’s
take one neuron in particular, and this neuron has a chloride pump on it. And so if this
is a chloride pump, we’re pumping chloride ions from a low concentration toward a high
concentration. So if we’re pumping these ions out of the postsynaptic cell and into
the extracellular fluid, that’s creating a gradient. So by using the chloride pump,
we create a chloride gradient. So what this does then is we can have a neurotransmitter
come in and bind to your chloride channel; and this is fast, so this chloride channel must be
ionotropic. And when the neurotransmitter binds to this ionotropic chloride channel,
the chloride channel opens. When the chloride channel opens, which way will chloride ions move?
They’re going to move into the cell, because we use the pump to create that gradient.
So chloride ions—we have a chloride influx, they move into the cell. So when they move
into the cell, they’re carrying what charge with them? That'd be a negative charge,
and hence, they’re bringing more negative charges inside the cell. So we’re hyperpolarizing
the membrane. And when we hyperpolarize this postsynaptic membrane that decreases our chances
of generating an action potential on the postsynaptic cell.
So this is just one mechanism for using chloride channels to generate a fast IPSP. Here’s
a second mechanism. So on other neurons the goal then of the chloride channels is to stabilize
the membrane potential. So let’s look at how we could stabilize the membrane potential
by using chloride channels. So to begin, let’s start with this channel here. And this is
a leak channel, and this leak channel allows your chloride ions to move through the leak
channel. So via this leak channel, your chloride ions go to equilibrium. In other words, I
have no gradient for my chloride ions. So if there’s no gradient, think about what
will happen. Now these leak channels are always operating on these types of neurons. So now,
in step two, our neurotransmitter binds to the chloride channel. And again, this would
be an ionotropic channel because this is a fast response. When the neurotransmitter binds
to the chloride channel, the channel will open, and what happens? Do we have a net influx
of chloride ions? Hopefully you said no. The reason that we have no net movement of chloride
ions is because there’s no gradient for your chloride ions. So because there’s no
net movement of the chloride ions—so in other words, there’s no net negatives coming
in, there’s no net negative going out—this will stabilize the membrane potential. So
that’s a second way that we can create an inhibitory postsynaptic potential on some
neurons. Here’s the third way to generate a fast inhibitory postsynaptic potential,
and this could occur on other types of neurons. So on these types of neurons, we still have
the leak channel that we just discussed. So through these leak channels or due to these
leak channels we have no chloride gradient because those—of those leak channels allowing
chloride ions to go to equilibrium. But here’s the difference: We can have an excitatory
neurotransmitter bind to a receptor, and when this ionotropic receptor or channel opens,
we get a positive influx. So whatever this ion is, it’s a cation. So we get positive
charges being influxed into the cell.
Now, we can have another neurotransmitter being an inhibitory neurotransmitter. So for
the inhibitory neurotransmitter, it also binds to an ionotropic receptor, but this is a different
receptor. And the channel opens…and when the channel opens, chloride ions move into
the cell. Hopefully you’re questioning this, because we have no concentration gradient
for chloride ions because of the leak channels here in number one. So why is it that chloride
ions can move into the cell if there is no concentration gradient? The reason the chloride
ions can move into the cell is because we have an influx of positive charges, and that
attracts the negative chloride ions into the cell as well. So now your chloride ions are
not moving based on a chemical gradient, they are—their driving force is electrical. Because
the inside of the cell became a little more positive, chloride ions were attracted to
that and they moved into the cell as well.
Now let’s look at the overall effect of this then. So we have negative ions and positive
ions moving inside the cell. And it’s a one for one, so these cancel each other out.
Each positive cancels out each negative. Therefore, if we’re cancelling them out, has the membrane
potential changed at all? Hopefully you answered no. So we have no change in the postsynaptic
membrane potential. Therefore, we have stabilized the postsynaptic membrane potential at negative
70 millivolts. So these inhibitory postsynaptic potentials once again are graded potentials.
So again, please remember and always visualize what we’re doing. This is our presynaptic
neuron, here’s the postsynaptic neuron. And what we’ve got is an increase in the frequency
of action potentials traveling down the synaptic neuron. So when you increase the frequency
of action potentials coming down the presynaptic neuron, that means you’re going to release
even more neurotransmitters. Remember that these are inhibitory neurotransmitters, that’s key.
So if you have more neurotransmitters being released that means more of them can
bind to the postsynaptic cell. But now we want to think about how does this affect the
chances of the IPSP reaching the axon hillock? Remember that these are inhibitory. So the
more inhibition you have on the postsynaptic cell, the less likely you are for that IPSP
to reach the axon hillock. So if you have low chances of your IPSP reaching the axon
hillock, that means you have decreased your chances of generating an action potential.
After all, that’s what an I, an inhi–an inhibitory postsynaptic potential do—does;
it decreases your chances of generating an action potential on the postsynaptic cell.
Now just as a little reminder here, after a postsynaptic membrane has gone through either
an excitatory postsynaptic potential or an inhibitory postsynaptic potential, either way,
your neurotransmitter has to be removed from the cleft. And in order to be removed
from the, from the cleft–and remember why, right? Why do we want to remove neurotransmitter
from the cleft? Well, as long as the neurotransmitter is there, you will keep responding to
the environment. So for example, if you put your hand on a hot stove, you want to withdraw
your hand once and then the response should be over. So you have to get rid of the neurotransmitter
to shut off that response. So remember that there are three ways to do this. One is for
the neurotransmitter to diffuse away; so it diffuses away from the synapse and it’s
later degraded. The other way is to degrade the neurotransmitter in the cleft by using
enzymes, and that occurs right in the synapse. And then the third way to get rid of your
neurotransmitter in the cleft is to do reuptake.