Welcome to this tutorial on the Ionic Basis of the Resting Membrane Potential. This tutorial will relate to one of the core concepts in the field of neuroscience. It's core concept number two, as defined by the society for neuroscience. I would encourage you to visit BrainFacts.org and navigate to core concepts to learn more about what these concepts are all about. but for our purposes, it's useful to just highlight how this tutorial, right now, related to the broader field of neuroscience. And it does so, because we're going to begin a discussion about how neurons communicate. Using electrical and chemical signals. The concept for today's tutorial, the resting membrane potential, really sets the stage for all manner of communication among neurons. I have some learning objectives for you today. I want you to be able to describe the concept of electro-chemical equilibrium. And relate this concept to the resting membrane potential of neurons. I want you to be able to explain why the permeability of the neuronal plasma membrane at rest to potassium ions. The concentration gradient of this ion across the neuronal plasma membrane together account for the resting membrane potential of neurons. I want you to do so in a rather formal way. I want to introduce to you something called the Nerst equation, and challenge you to use the Nerst equation to predict the resting membrane potential of neurons given knowledge of the concentration gradients of permeant ions. Okay, well let's begin. Okay, to begin with let's consider two important mechanisms that support all manner of electrical signaling that we find in nerve cells. These mechanisms are supported by two very different kinds of proteins that we find in membranes of neurons. One type of protein is an ion pump, or an ion transporter. It's illustrated on the left hand side of the slide. What these pumps and transporters do is translocate ions. From a region of low concentration to a region of high concentration which is why I've drawn this large arrow over to the left indicating an active mechanism that's pumping ions up stream, if you will, that is against the concentration molecule binds an ion from a region of low concentration inside the cell and delivers it across the membrane to a region of high concentration, there's the to be an example of active transport. Now, on the right side of this slide, we have an illustration of the second kind of mechanism that's critical for neuro-signaling. Once we establish concentration gradients of ions, we can discharge those gradients to create electrical signals. But that requires some means of regulating the permeability the neuronal plasma membrane to a permeate ion. And this is accomplished via the function of ion channels. So these are integral membrane proteins that create aclei's pore for the passage of an ion from a region of high concentration to low concentration. So what we see on the right is a means for allowing for ions to diffuse down their chemical concentration gradients. So I want you to see how these two mechanisms work hand in hand. Pumps establish the concentration gradients that provide the driving force. For the diffusion of ions across the neuronal plasma membrane. Now, in order to understand how all this works and the significance of ions passing across a permeable membrane, let's begin by considering a simple model system. So, in this case what we have is a semi-permeable membrane that divides some kind container into two kinds of compartments. And that membrane has ion channels in it that allows for the passage of potassium ions. So, what we've done here. Is we've simply filled a container with a one millimolar potassium chloride solution, with this membrane running right down the middle. So under these conditions, potassium ions are free to pass from one side of the membrane to the other. And there is no net flux of potassium. That is, just as much potassium goes to one side as back across the membrane and to the other. And as a result if we were to insert wires into either side of this chamber, and then record a electrical potential. We'd see that there's essentially no potential difference that is the voltmeter would record a potential of zero. Now, imagine what would happen if we replaced the solution on one side of this chamber, let's say on the left side of the chamber, with a ten millimolar potassium chloride solution. Such that on the left side, we'd have ten times the concentration of potassium as on the right. So, if we were to do this kind of an experiment, what we would find is that, very quickly, we would go from the condition to some kind of equilibrium. And that equilibrium will be established as potassium ions diffuse down their concentration gradient from the left side of the chamber to the right. Now, what will happen? Well, potassium ions will move, and potassium ions carry a positive charge. So, as potassium ions diffuse down their concentration gradient, what we will discover is the accumulation of positive charge on the right side of this membrane. That is the right side of this membrane will become slightly positive, relative to the left. And in a complimentary fashion, we'll have the accumulation of the negative charge. On the left hand side of this membrane in the compartment of higher potassium chloride solution. So the positive charge is conveyed via potassium ion. The negative charge is reflected in the dissociation of chloride ion from the potassium chloride compound. Now, of course, these movements of ions across this membrane happen in just an instant. So this equilibrium is established very quickly. And what will happen at equilibrium is that an electrical potential, will become established across that membrane. With a predictable magnitude of that potential. In fact, in this case, the potential has a magnitude of 58mV with compartment number 1 on the left hand side the 58mV negative to compartment number 2 on the right hand side. So, when we establish electrochemical equilibrium, we have achieved a state at which the flux of potassium ions from one side of this membrane to the other side This is in fact the definition of equilibrium. So let me repeat myself and try to make this even more clear to you. So as potassium diffuses down it's concentration gradient and electrical force builds up that is exactly equal and opposite. To the strength of the chemical gradient. So in conceptual terms we have a conceptual gradient because we chose to put on one side of this membrane a tenfold more concentrated solution of potassium chloryde. But once that was done, potassium diffused across this semipermeable membrane to the point where an electrical gradient was established that's equal and opposite in magnitude. And that gradient, as measured by our volt meter, is precisely minus 58 mV. And I want you to understand intuitively. No so much quantiatively, but intiuitvely, what that magnetude of electrical potential actually is. And how to get a feel for understanding changes in that potential across the in the membrane if you know something about the permeant ions and their concentrations. But before we get to a more formal and quantitative approach to understanding this memory potential at equilibrium. Let's just emphasize again the key factors that are responsible for setting up this potential in the first place. The key factors that are needed for the generation of this bio-electrical potential are a mechanism for establishing the concentration gradient. And that happens via the activity of ion pumps and ion transporters, as illustrated on the left hand side of the figure. Now, we established the concentration gradient. But there will be no membrane potential unless there's the passage of ions through some permeability channel. And that's where the integral membrane protein that creates and ion channel comes in. So the ion channel allows for this membrane to be selectively permeable to a particular ionic species. Now, for real neurons in real nervous systems, both of these mechanisms. Are in operation with respect to potassium ions. In fact, at first approximation, the movement of potassium ions across a semipermeable membrane is sufficient to explain the resting membrane potential of neurons. Now, I'd like to make just a couple of other points as we Pass through this discussion of resting membrane potential. One is that we don't actually have to move a large number of potassium ions in order to establish this potential. So it happens very quickly, and it happens with the movement of a relatively small number of ions. And as a consequence we really aren't fundamentally changing the concentration of solutions on one side of that membrane or another. So we still have a ten milimolar solution on one side, a one milimolar solution on the other in our module system. Another consequence is that because we have chloride ion on either side of our membrane and that chloride ion has no channel, in this model system anyway that will allow it to permeate. We can establish overall electrical neutrality. that is to say That while there is a separation of charge on either side of the membrance the solutions themselves on The positive charge is balanced out by negative charge. And then lastly I would say that the separation of charge is really only limited to this membrane. Sometimes I like to think about being inside of a cell and maybe the walls of this room being the plasma membrane surrounding this wall and if there's overall electrical neutrality I can move But if I were to touch the wall, such as what I might do. If I were to touch the wall maybe I would get a bit of a shock because the Well, I'm not sure how well that worked for you on camera, but I think you get the idea. So the separation of charge is limited just to the perimetery of that cell. That is to either of the neuronal plasma membrane. From time to time, I'm going to point you to what I think are pretty helpful animations that are at the website that supports the textbook. That I'm recommending that you read as we work through these tutorials in medical neuroscience. So, if you follow the link in the handout that I gave you or if you navigate to the website from Sinauer Associates that supports neuroscience fifth edition, you'll get to a series of animations. And I would direct your attention to the animation in Chapter 2, called The Resting Membrane Potential. So if you simply click the link in the PDF file, that should take you right there. Otherwise, you can navigate there on your own. And helpfully, you'll find this animation a useful summary of what we've discussed so far. And even more.
