Welcome back. We're going to be talking in this session about action potentials. These action potentials are going to be another major way that neurons communicate. We'll talk specifically about their role in communication but we will start talking about the ion channels that are important and that are necessary to have in action potential. An action potential is going to be a very specific kind of change in membrane potential. The reason why action potentials happen instead of a graded potential is because of the types of channels that are present where we have action potentials. Instead of being channels like the ligand gated ion channels we talked about with graded potentials. For action potentials, you must have voltage-gated channels. We're going to talk about the voltage-gated sodium and potassium channels that are going to be so common in forming an action potential. The fact that their voltage gated means that a depolarization of the membrane. when the membrane becomes more positive, is what gates them. This is what causes them to open. That's what's shown in this fist spot where they start off closed. Then we have depolarization. That causes them to open. However, keep in mind the sodium channel is always fast to make these changes to its structure, and the potassium channels are slow. So sodium is going to be fast and the potassium is going to be slow. So, the sodium channels are going to open first. The sodium channels are going to allow sodium to rush into the cells. That's what happening here in this next spot. Whereas, the potassium channels they've still been stimulated by that depolarization. However, they just haven't opened yet. After a little bit of time, then what happens is the potassium channels have finally opened in response to the stimulus. But in that same amount of time, you see this little structure has now closed or filled in the opening of the sodium channel. When that happens, the sodium channel moves to an inactivated state. This means that it not only is no longer moving sodium ions into the cell but it also can't be opened. That's why it's called inactivated. It's different from being closed. At this third time point, then we only have potassium moving out of the cell. As potassium moves out of the cell, then that means the membrane potential is starting to head towards the equilibrium potential for potassium. This repolarizaton of the cell then causes the closing of both the potassium channel and the closing of the sodium channel. Now, we know it was in the inactivated state and it wasn't moving sodium ions. But once it returns to the closed state, then it can be opened with another change in the voltage. So this properties of these voltage gated channels are what form and give the properties of the action potential. This property of the sodium channel being inactivated until the membrane potential comes back down to rest. is also a very important aspect of the action potential. Let's talk about why it's important. Tt's responsible for the property that we call the refractory period of the action potential. This is a period while those sodium channels are inactivated. No matter what you do to stimulate the membrane, they're not going to open. You're not going to have another action potential. We'll see why that's important soon. Let's put together these properties of these channels. What that's going to mean for the membrane potential when an action potential occurs. In our state 1 here, we are at rest. Then, you can see the next step 2 is that we have some stimuli. These stimuli are very often going to be graded potentials. So that say on our membrane we're releasing a little bit of neurotransmitter that binds to some sodium channels causing them to open. Then sodium rushes in because of its chemical and electrical gradient. That's going to cause a little bit of an increase in the membrane potential in that spot. This diagram shows two sub-threshold stimuli. They don't go high enough, they don't depolarize the membrane enough, to open these voltage-gated channels. So they just die out as graded potentials do. Nothing happens. But if we get a stimulus that’s great enough, that gets the membrane moves to threshold. That is when the sodium and potassium channels will open. That's when we'll get to stage 2, which we’ll remember we said both channels are going to be activated by this reaching threshold. But that sodium channels are going to open really quickly. So, that means in stage 2, we have only sodium channels open. So sodium's going to rush in, that's going to make the membrane more positive or the membrane potential more positive, which then is going to open more sodium channels. And so we're going to have a positive feedback cycle going on where we bring in more and more sodium and open up more and more more sodium channels. Then the membrane potential is going to head towards the equilibrium potential for sodium because we have only sodium channels open. So that's what's happening in stage 2, we're getting a huge depolarization and overshoot. In stage 3 now, we've had a little bit of time pass and so we've got 2 things happening. One is now there's enough time that the potassium channels have opened and there's been enough time that now the sodium channels are in the inactivated state. Which, remember, means they're no longer moving sodium and they can't be opened right now. So, if we've got only potassium channels open, then membrane potential is going to head towards the equilibrium potential for potassium. Those potassiums are going to rush out of the cell based on both the chemical and electrical gradient at this point. So, we're going to have a big repolarization of the membrane in stage 3. In stage 4, now we've come back down to rest. Now we're starting that reset of the channels. Where the sodium channel is going to be able to close, which is what's shown here. It could, in theory, be opened at this point. The potassium channels are going to be slow to close. They're still going to stay open. That's why we're going to go below and get to the equilibrium potential for potassium. But then in stage five, finally the potassium channels have caught up and now they're closed. Then, we're going to get back to rest through the actions of the sodium-potassium ATPase which gets our gradients back in order where they should be. Keep in mind, with all of these big changes in the voltage of the membrane, we're moving very few ions. Our chemical gradients, our concentration gradients are not changing appreciably, even though we're having these huge swings in the membrane potential. So based on this, you can see how this is different from a graded potential. If you don't reach threshold, nothing happens, but as soon as you reach threshold, you're going to have the same response no matter what. You're going to have an action potential, so it's an all or nothing phenomenon. We'll talk many times about this property and what that means for what the nervous system can accomplish. We'll also talk about how this is not going to decay over a distance. That's what shown here. So, remember we've talked a little about or we're going to be talking about the fact that these voltage gated channels (that mean that an action potential can occur) are going to be in an axon. Here's a neuron with an axon and we're saying that right here, we can have an action potential. It will travel down the axon. At this point where this action potentials is occurring, sodium is rushing in and it's going to then depolarize the membrane in the neighboring area. That it's going to get that part of the axon above threshold and cause it to have an action potential. So we had an action potential right here and then it stimulated this area right here to have an action potential. That's what's happening right here, which is then has stimulated this area to have an action potential, so we've got sodium rushing in right here. Now, you can see when we're having action potential right here, we have sodium rushing in and it's diffusing in all directions. However, this area right next door is still having its action potential and so, it's still highly depolarized. This means those sodium channels are still in the inactivated state. So we can't have an action potential right here where we're still having one. We can only have one downstream in this direction. onsequently, once we get started here we can only move the action potential down the axon. Now, if we started in the middle that would be a different issue but since we always start at the initial segment in the neuron, then we're going to have a unidirectional propagation of the action potential. It's because of that refractory period of the sodium channels when they're inactivated. So, this is where we're going to talk about the different parts of the neuron and what channels are expressed where. So, really to make things simple, you can think about the fact that the dendrites and the cell bodies are going to tend to have ligand gated ion channels. Which means these are going to the parts of the neuron that are going to be responsive to neurotransmitter. They're going to be the parts that are going to have a synapse from another neuron which releases neurotransmitter. The dendrites in the cell body are going to have the ion channel that respond to those neurotransmitters. That means that the dendrites and cell body will have graded potentials. The axon is going to be different. It's going to be where you have the concentration of the voltage gated channels. That means that's where you're going to have the action potential. Specifically right here in the initial segment, the site where that axon meets the cell body is where you're going to have a super high concentration of this voltage gated channels. So that if whatever's happening with the dendrites or the cell body with the forming graded potentials is great enough to get this little spot above threshold. Now remember, they're going to decay over time and space and be proportional to the stimulus but if they're great enough, then we will cause an action potential. So in this way, you can think of the cell body and the dendrites as kind of the place that's summed, all those signals are summed through graded potentials. If the stimulus is high enough, then the initial segment will take that information and decide whether or not to have an action potential. We'll talk about this much more right now. So this is the idea of having multiple synapses so multiple inputs through graded potentials. Imagine that we're measuring the membrane potential at the axon initial segment. We know if a membrane potential goes above threshold at the axon initial segment, then we're going to send an action potential down the axon. So here we have synapse 1, where when that neuron releases a little bit of neurotransmitter. It causes a little bit of depolarization of the membrane that reaches that acts on initial segment. Let's say it causes some sodium to enter the neuron. Synapse 2, when it fires, in this case, causes an even larger stimulus, so maybe it's closer to the axon initial segment. So then there's more of those positive charges that enter when those sodium channels open. This reaches the initial segment to make a larger depolarization there. Then we have synapse 3, which is actually causing a hyper-polarization of the membrane. Perhaps it's causing ion channels to open that let chloride into the cell or let potassium out of the cell. So we get a hyperpolarization when synapse 3 fires. Since these graded potentials are additive, then they are additive when you look at the axon initial segment. So if we have firing of one and two at the same time, we get a larger effect and we get closer to threshold than if either one of them fired by themselves. We can also have and additive affect with a positive or an excitatory and an inhibitory synapse. In that case they kind of cancel each other out. Then, remember we can also have repeated stimuli. S we might not just have a greater stimulus. But very often the nervous system is going to signal by having repeated actions potential, so repeated stimuli. When that happens, then they can be additive. In that way, get to threshold so that we have an action potential. So this is what we're talking about when we're talking about the axon initial segment integrating information. It's allowing these graded potentials to be additive. If they're strong enough, then they cause an action potential. The last thing we're going to talk about with action potentials is the role of myelination. We talked about how the myelinate portions of the axons leave a space, which we call the node of Ranvier. This is a bare spot of the membrane that isn't electrically insulated by the myelin. It has a large concentration of these voltage gated channels. What that means is if we have an action potential, for instance let's say it's happening at this node, the sodium rushes in, that is positive charges rush in. Because of that myelination does not allow leaks of the sodium across the membrane, it is really insulating it. Then that means that the effect of those positive charges of sodium, instead of just being felt here, are felt all the way down here in the next node. They're also felt down here in the previous node but we're saying that's the spot that just had an action potential and so here the sodium channels are inactivated. It doesn't matter that the depolarization is felt at the node. They just fired. It does matter that it's felt at this downstream node. In this way the fact that the action potential can jump from node to node, the effects of the action potential are felt further away because of the insulation. This allows the transmission of the action potential or the conduction of the action potential to happen much more quickly. Instead of having to have an action potential here and then an action potential here and then an action potential here, it just has one at the node and then at the next node. So it's very rapid. So there are two main ways that an axon can have characteristics that allow for very fast transmission, which is important for certain modalities such as touch. Certain sensory axons are myelinated. Some will be unmyelinated if it's not as important for fast transmission. The other factor is the diameter of the axon. It's just like a wire where if you have a thicker wire, a wire with a larger diameter, then current will travel down it more quickly because there's less resistance. Because there's more paths to choose because it has a larger diameter. An axon behaves just in the same way. A larger diameter axon has lower resistance. Axon potentials will travel faster down a large axon that's myelinated. So to wrap this up, we've talked about an action potential which is going to be where you have sodium, come in to the cell which causes a large depolarization. And then, potassium leaves the cell. This causes a large repolarization. The fact that that's going to be all or none, and that there will a refractory period, which means that the cell needs to come back to rest in that location before another axon potential can fire.
