Welcome to this tutorial on the Propagation of Action Potentials. This is the final tutorial in a set in which we've been considering the ionic basis of the resting membrane potential, the action potential. The molecular mechanisms involved in the generation of action potentials. And now, we're going to talk about how these signals propagate along the length of an axon. So welcome to my home. It's a chilly, rainy evening. I suspect you can probably hear the rain falling in the background. So please don't mind that. It may sound a bit staticky but it's really a lovely sound from where I'm sitting. And I hope you can enjoy that with me this evening. Well, let's begin. Once again, our story today on the propagation of the action potential. Pertains to, our second of our eight core concepts in the field of neuroscience. That is, that neurons communicate using both electrical and chemical signals. Our learning objectives for today are that I want you to be able to describe the ionic basis of the action potential. In terms of the voltage in time -dependant changes in ionic permeabilities that occur across the neuronal plasma membrane. Same learning objective you saw with our last tutorial. But now what I want you to do is to apply that knowledge to the concept of propegation of action potentials along a lenth of axon. And that brings us to our second objective, and that is to consider the benefits of adding myelin to an axonal sheath. So I want you to be able to characterize the advantages of myelin for the conduction of a l-, action potential along an axon. Well, in order to set the stage for what I want to discuss with you today. I'm going to recommend that you pause for just a moment and view animation 2.3 at the website that supports our textbook. This animation will account for you again the ionic basis of the action potential. You can click on the hyperlink that's part of your tutorial notes. Or navigate yourself to the website that supports our text. Okay well, I think we're ready to move on. And let's consider for a starters some of the properties again of an axon. And some of the limitations that need to be overcome as we consider what it takes to propagate an action potential. Now, you'll recall a point I made right at the start of the course, and that is that; neuronal membranes apparently poor conductors of electricity. One reason for that, of course, is that these membranes tend to be somewhat leaky. They just don't allow for the conduction of electrical charge very efficiently. And this phenomenon is illustrated with. The application of a relatively weak electrical signals to a length of an axon. So we might call this a sub-threshold stimulus one that is not going to depolarize neuron sufficiently to reach threshold for falling an actual potential. So threshold in this particular axons is around minus 50 millivolts. And even right near our stimulating electrode, we record a depolarization of only about seven or eight millivolts. So, not sufficient to bring this neuron from minus 65 to minus 50. But that's okay. This experiment illustrates the point that all we have to do is travel a relatively short length down this axon. Just a few millimeters, and already there's significant decay of the current that's been passed at a particular site. So without the presence of myelin, an axon by itself is just not going to provide, sufficienct conduction through purely passive means. Now, when we talk about the passive flow of current along an axon, this is essentially what we're talking about. With the sub-threshold depolarization, all we have is passive current flow down this axon. And due to the leakiness of the membrane, especially in the absence of myelin, there's just not much hope of conducting the electrical signal more than a millimeter or so. But thankfully, there are indeed active properties that can facilitate the propagation of an action potential. So now, let's look at a length of axon that is stimulated with a stronger stimulus. Such that the local region of the membrane is depolarized sufficiently to achieve threshold for firing a action potential. And then let's watch what happens. Okay. This is a bit of a busy figure from your textbook, figure 3.10. But I think it illustrates quite nicely the basic phenomenon that we want to consider. Let me just set up this figure for you, just a little bit. So we have three moments in time. That are illustrated. Time 1, time 2, and time 3. And then we have three locations along the axon that are illustrated. Point a, point b, and point c. So let's begin at time equals 1 and point a. And so this, in fact, will be the site at which we stimulate this axon by injecting positive current at this local site. Now, if we inject sufficient current to depolarize this membrane beyond threshold. What we will have is an action potential. Okay? And that action potential, as you now know, involves the voltage dependent opening of sodium and potassium channels. First sodium, very quickly, and that allows for sodium to rush in through these open sodium channels. And that sodium now triggers the passive movement of charge along the length of this axon. So that charge is going to go in both directions, away from this side of stimulation. Now let's see what's happening as we move from point A to point B. Positive charge is flowing as indicated by the red shading in the middle of the axon. And as we reach point B, now, if there is sufficient depolarization of this membrane, the next batch of sodium channels are going to open up, sodiums going to rush in. And the wave of depolarization is going to continue in this direction from point A to point B, and now from point B to point C. But let's return upstream to point A where we initially stimulated to consider what's happening. Recall that the opening of potassium channel lags behind the opening of sodium channels. So this means that while an action potential has been triggered and depolarization has reached point B, at point A now. What we have is the opening of potassium channels and the efflux of potassium ions. This means that The initial site of stimulation is now engaged in the process of repolarization. This, in essence, puts a brake on the back propagation of the action potential. Allowing the signal to propagate. Primarily in the downstream direction from the site of stimulation to outward. Okay. So, now let's arrive at point C and as with point B, the depolarization. Is sufficient to open enough voltage-gated sodium channels that the inward sodium current is greater than any lake of potassium current and any voltage dependent efflux of potassium. That means that sodium is going to rush in, that positive cycle is going to be regenerated and The action potential will continue to propagate. Now, if one is to put a recording electrode at each of these points. What we'd see is that, at time 1, at point A, we have an action potential. At point B, a little later in time, we have an action potential recorded. And further along the axon at point C, and a little later in time, we can likewise record another action potential. Now while point C is firing its action potential, again the process of re-polarization is taking place upstream at point B. So potassium ions are leaving. As the potassium channels open more slowly, and that again puts a bit of a blockade on the backwards propagation of that action potential. So this slower negative feedback loop in essence helps to push the action potential Down in a direction that, for most axons, would be physiological. Now, let me make a point about nomenclature. We talk about the propagation of an action potential. Or the conduction of the action potential, as if something's actually moving. Well, what's moving as charge within the cytoplasm of the axon. But really, what I think you can appreciate is that the action potential is being regenerated at each of these points A, B, and C. One additional point to make before we leave figure 3.10. And that is the importance of passive current flow. The passive current flow that I've been speaking about refers to this movement of charge down the axis cylinder of the axon. And, as you know from your studies of the movement of fluids through tubes from physics That the greater resistance. Then, the less flow there's going to be, down that cylinder. The same is true for the movement of charge. So, small diameter axons impose greater resistance to the axial diffusion of ions. Or the axial conduction of charge. Larger diameter axons are for less resistance and facilitate the rapid conduction of passive current. This is why small diameter axons will have a slower propagation rate of action potential conduction. Compared to larger diameter axons. So one way to speed up action potential propogation is to incrase the diameter of an axon and vice versa. Okay, now what about myelin. How does myelin contribute to the propogation of action potentials. Well, I would remind you that myelin is produced in the central nervous system by oligodendrocytes. In peripheral nerves in the body, myelin is made by Schwann cells. But we're focused mainly on the central nervous system in this course so I'll use as our example for myelin forming cell the oligodendrocyte. So, you'll remember that the oligodendrocyte grows out a plasmalemma or a layer of membrane, that then wraps around a segment of axon. The length of that segment is typically about a millimeter, sometimes, More, sometimes less, but typically a millimeter. And at the junction of a myelin sheath that's formed by one cell and different cell, is a gap. And that gap is known as a Node of Ranvier. And at this gap we have a concentration of Ion channels. Channels for sodium and channels for potassium, allowing for the regeneration of action potentials at the Nodes of Ranvier. In between the Nodes of Ranvier, we have a tight wrapping of myelin. Which serves to increase the passive current flow by making the myelinated segment of axon much less leaky than it would be otherwise. So more charge is effectively transferred from one node to the next. There's another advantage here to the presence of myelin. And that is that this Node of Ranvier presents a limited space for the concentration of ion channels. Without myelin to ensure effective propagation of axon potentials, one might imagine a much larger number of ion channels would need to be inserted into the membrane in order to ensure propagation. But with myelin, a smaller number of ion channels can be concentrated in, much less, surface area along the axonal plasma membrane. So this leads to greater efficiencies as well as greater, speed of conduction. So let's look at how this works. Consider a similar kind of an experiment. Looking at a length of axon at three points in space along the length, but also at three moments in time. And consider what happens when a stimulus is applied, let's say to point A. So when this happens, as we saw previously, voltage-dependent sodium channels open, sodium rushes in. And positive charge can now very effectively and very rapidly passively diffuse down along the length of myelinated axon. Until the next Node of Ranvier is reached. We'll call that point B. Here, sodium channels are opened. More sodium can rush in as the action potential is regenerated here. The net positive charge, now again, effectively, passively Defuses down that axon and reaches our third point, point c, again regenerating action potential as sodium ions rush in. Meanwhile upstream at each of these sites, there is the delayed opening of potassium channels. So, potassium flows out. The membrane repolarizes again putting the brakes on the back propagation of that action potential. The same would be true, of course, with the repolarization of the membrane. At site B. As an action potential is generated one nodal length. In the downstream direction at point C. So, the advantages of myelin is really twofold. One is an increase in the propagation of action potentials in terms of both efficiency and in terms of the conduction velocity. But also there is an advantage of economy. Fewer ion channels need to be produced by the cell body and inserted into a much more reduced surface area of axonal plasma membrane. Now, let's compare the generation and propagation of action potentials in an unmyelinated axon that might be sitting in a spinal nerve right next to a myelinated axon. The unmyelinated axon might be a post ganglionic axon derived from an autonomic nervous system neuron. The myelinated axon could be a sensory or motor fiber present in peripheral nerve. And if we stimulate, nearby locations along that nerve. We might drive sodium into both of these axons and trigger an action potential at the same time in the same place. But because of the presence of myelin, the propagation of positive charge is going to be Much more rapid and much more efficient in the myelinated axon compared to the unmyelinated axon. And so we are able to generate the second action potential efficiently at the next node in just a fraction of a second. Meanwhile, in the unmyelinated axon. In order for there to be effective conduction of action potentials. We need to put very many voltage dependent sodium and potassium channels along the length of this membrane, to ensure the regeneration of action potential at each adjacent point along its length. Now, as we continue to move down that axon, we see that at least in this illustration, we've about doubled the relative conduction velocity of the mylenated axon compared to the unmylenated axon. Again, with the additional advantage, a fewer ion channels are needed, only at the nodes to regenerate the action potential. Compared to what must be necessary in this un-myelinated axon where the action potential must be regenerated at each adjacent location in the membrane. Now there's a term for the type of conduction that we see in the myelinated axon. It's called saltatory conduction. Which means, to jump. So, the implication is that the action potential jumps from one node to the next, along the length of this myelinated axon. And it's because the action potential need not be regenerated along each adjacent segment of membrane. Because of the efficiency of the passive flow of current along the length of the myelenated segment. Action potentials only need to be regenerated at each node. So there's this jumping of signal from one node to the next to the next to the next along a myelinated axon. So, I'd like to leave you with a study question that will challenge you to consider how these concepts might play out in a clinical condition. That might affect the integrity of myelin sheaths around axons. One of the, more common conditions that can produce this result is multiple sclerosis. So consider the study question that you can find here, as well as at the bottom of your tutorial notes, and respond accordingly. Lastly, I would encourage you to view animation 3.2. You can do that by clicking on the hyperlink in your tutorial notes document or follow the your browser's navigator to the website that supports our textbook. And view animation 3.2, Impulse Conduction in Axons. And hopefully that'll give you yet a different take on this important concept of the propagation of electrical signals along the length of an axon.
