Hello. Welcome to our second session about the nervous system. We're going to talk about membrane potentials. Membrane potentials are changes or differences in the amount of charge on either side of the membrane of cells. In particular, we're going to talk about neurons. This is going to be our first introduction into the method of communication in the nervous system. Dr. Jakoi has already talked to you about the electrochemical gradient. These are chemical gradients of electrically charged molecules. She told you how the sodium potassium ATPase is so important in establishing these gradients. We'll talk more about that later. The whole point of this, our bodies spend a significant portion of their ATP setting up this gradient, and they do it so that they can harness the gradient to do different jobs. Sometimes they use the potential energy that's in that gradient to help transport certain substances across the membrane. We'll be hearing about that in other organ systems. But the other thing they can do is use this gradient to allow ions to flow across the membrane and form a current that can be used in signaling. That's what we're going to be talking about for the next several minutes. One thing that you need to remember, and you don't need to remember these concentrations down here at the bottom of the slide, but what you do need to remember is that the sodium potassium ATPase is going to make a larger concentration of sodium on the outside of the cell compared to the inside of the cell. There's much more potassium on the inside of the cell compared to the outside of the cell. We'll see in a few minutes why this is really helpful. We've taken two different positive ions and segregated them to two different sides of the membrane, basically. We'll see how that's advantageous. The other thing to keep in mind is that in neurons and in many other cells of our body, when those cells are at rest, there is what we call a negative membrane potential. That's what's shown right here. What a negative membrane potential refers to is the fact that there are more negative charges inside the cell than outside of the cell. We're going to talk about that in much greater detail as well. So, we've established that in a normal cell, we have a lot more sodium on the outside and a lot more potassium on the inside. That's what's shown here in a simplified system on this slide. Here, we have a 150 millimolar potassium chloride on the inside of the cell and 150 millimolar sodium chloride on the outside of the cell. Since these are potassium chloride and sodium chloride, there are equal numbers of positive and negative charges on each side of the membrane. Right now, the membrane potential equals zero millivolts. There's no charge difference between the sides of the membrane. Also, you'll note in this figure that we have some ion channels. These are the blue boxes. There are several things to keep in mind about ion channels. One is that they're specific. These happen to be potassium channels, which means that they're only going to transport potassium for all intents and purposes. Sodium is not going to be able to go through these channels in any perceivable manner. They're specific for potassium and they're going to be gated. This makes sense. If you spend ATP to segregate sodium and potassium to build this electrochemical gradient, you don't want ion channels just sitting there, open and unregulated, that let the ions flow down their concentration gradient. You want ion flow to be highly regulated if you're going to put so much energy into building the gradient. So, these will be gated. We'll be talking about the different modalities that can gate these channels. Then the other thing to keep in mind is that when the channels are open, they're bi-directional. Potassium's going to be able to move in either direction across these channels, depending on both the chemical gradient that's present and the electrical gradient. So, in step 2, that's what's happening. We are opening a potassium channel. As we do that, we've got no electrical gradient. We have a very large chemical gradient for potassium. So, potassium is going to leave the cell. As soon as one potassium leaves, then all of a sudden, we've got a excess of negative charge on the inside of the cell versus the outside. Now we've got a negative membrane potential. Potassium is going to continue to diffuse through the channel, down its concentration gradient. So we're going to get more and more positive charges on the outside of the cell, and more negative membrane potential for the cell, until finally, in step three, we've got enough positive charges outside of the cell that now the electrical gradient drives some potassium back into the cell. So we've got more potassium leaving, but now some potassium is starting to head in towards the cell. In step four, we've got the same number of potassiums leaving the cell as we have entering the cell. That's when we have reached the equilibrium potential for potassium. So, we still have a very large chemical gradient. Even in step four the number of potassiums that have left to form this electrical gradient is still very small. We still have a very large chemical gradient, but we have a large enough electrical gradient that it opposes the chemical gradient. The membrane potential, at this state, in step four, is positive. It is the equilibrium potential for potassium. So, what that number is in millivolts, it's going to be a negative number. I'm sorry, that's going to be a negative membrane potential. It's going to be based solely on what the potassium concentration is on the inside of the cell versus the outside of the cell. That's what's gonna determine the millivolt number. It is negative. It is the equilibrium potential for potassium. We're going to look at what this means for the cell in just a moment. But you can think of it this way, if we have only potassium channels open, and we have a certain concentration of potassium inside the cell versus outside the cell, if you just open those potassium channels, those channels only, then the membrane potential will become The equilibrium potential for potassium. Here's another way of looking at it. We said at rest, our membrane potential is going to be negative, which is what's shown right here. We'll talk about why that is in a minute. Now if we look at the case for sodium in a normal cell, we said it's going to have a much higher concentration of sodium on the outside of the cell. That means that if we open sodium channels, then sodium is going to enter the cell based on its chemical gradient but also based on its electrical gradient. Because we said at rest we have membrane potential. So that means that if we open sodium channels and let sodium keep entering the cell, the chemical gradient is going to have sodium come in until finally the inside of the cell is so positive that now sodium does not want to enter the cell. Because of the electrical gradient, it wants to leave. When we will get to a spot in a normal cell or in a neuron, this occurs about a positive 60 millivolts where there's so many positive charges inside the cell. The sodium still wants to come in because it still has a chemical gradient, but it now also wants to leave because the inside of the cell is so positive. At that point you've reached the equilibrium potential for sodium if only sodium channels are open. We can look at the same case for potassium which we have a little bit previously where we said it's gonna be more concentrated on the inside of the cell which means our chemical gradient is trying to get potassium to leave. But because our resting membrane potential is negative when we first opened the potassium channels, potassium wants to enter the cell. And so that means that if we open potassium channels and let the cell come to the equilibrium potential for potassium, that's going to be at a negative membrane potential when we have opposing and equal forces from the chemical and electrical gradient. So, basically, what the cell has done is it's taken two different positive ions, put them on opposite sides of the membrane so that they will have opposite charges for their equilibrium potential. We'll see how that is going to be harnessed in order for the cell to signal. So we've now established what an equilibrium potential is for a certain ion. That it's going to be based on the concentration of the ion. But now we wanna talk about how resting membrane potential is established. One thing we know is that we need to establish the electrochemical gradient. The sodium potassium ATPase is going to do that. When it does that, it's going to move three sodiums outside of the cell and bring in two potassiums inside the cell. So that's going to establish our gradient, but you'll notice that is sending out three positive charges and only bringing back in two positive charges. So the sodium-otassium ATPase is going to establish a little bit of a charge difference. This is going to cause a little bit of a negative membrane potential because of that difference in numbers of positive ions that it's moving. The other issue is what channels are open at rest. We said if only sodium channels are open, then the membrane potential is going to become the equilibrium potential for sodium. If we open only potassium channels, then the membrane potential is going to become the equilibrium potential for potassium. If we open both up, sodium and potassium channels, then that membrane is permeable equally to those two ions. Now the membrane potential will reside in between the two equilibrium potentials. It will be proportional to whichever ion is most permeable. If the membrane is equally permeable to sodium and potassium, then the membrane potential will reside between their equilibrium potentials. In the case at rest, we have the ATPase pump forming the sodium and potassium gradients. But we also have leak channels, which are going to be ion channels that let some ions through. They're going to determine what the resting membrane potential is. If we have a fair number of potassium leak channels and fewer sodium leak channels. then we have a greater permeability of the membrane to potassium. We have more potassium ions leaving through the leak channels then we have sodiums coming in through the sodium leak channels. That means our membrane potential at rest is much closer to the equilibrium potential of potassium. Now if we had only potassium leak channels, then the resting membrane potential would be the equilibrium potential of potassium. But since we have a few sodium leak channels operating, then the resting membrane potential is just a little bit above the equilibrium potential for potassium. It's another demonstration to determine what the membrane potential will be at any certain time, you need to know the concentrations of the ions, because those determine the equilibrium potentials. Then you need to know which ion channels are open, or how permeable the membrane is to one ion versus the other. When we talk about membrane potential changing, we have certain terms that we use. I'll be using them a lot so this figure is to help you with that. When we're at resting membrane potential, we say that the cell is polarized because there's a difference in charge across the membrane. It happens to be more negative. So, at rest a cell is said to be polarized. If for instance we open sodium channels so that sodium is going to rush in, then our membrane potential will increase and head towards the equilibrium potential for sodium. Now we say that the cell is depolarizing. It's becoming less polarized. The membrane potential is less negative. If it keeps going in that direction and then the membrane potential becomes positive, then you can call that an overshoot. If then we close the sodium channels, and then open potassium channels, then the membrane potential is going to head towards the equilibrium potential for potassium. Notice the membrane potential will head toward zero and then become more negative. That is called repolarizing. Now, the cell is becoming polarized again. If we keep those potassium channels open, then we will go more negative than the resting membrane potential and closer to the equilibrium potential for potassium, then the cell is hyperpolarizing. It's becoming even more polarized. It is at rest, even more negative. I'll be using these terms, so it's good to become familiar with them. You will hear them a lot when anyone's talking about changes in membrane potential. We're going to finish up this section talking just a little bit about a type of change in membrane potential. It gets confusing I think because we've talked about membrane potential, equilibrium potential. But what we're gonna start talking about now are types of changes in membrane potential. The type of changes shown in this image is called graded potentials. They're called graded because the amount of change in the membrane potential depends on the strength of the stimulus. So it can be graded, it can be a small change or large change, depending on the strength of the stimulus. I think the easiest thing to think about when you're thinking about a graded potential is to imagine that you have a ligand-gated ion channel. Meaning that it's gated by binding a ligand, which is very often a molecule like a neurotransmitter. Let's say we have in this image, a sodium channel that's gated by a neurotransmitter. It's sitting in the membrane. We add to that little spot in the membrane just a small amount of neurotransmitter. It's going to diffuse away from where we added it. But where it's most concentrated, it's going to be able to bind to the sodium channels and open them. This causes sodium to rush into the cell. This causes a small depolarization of the membrane. The membrane potential is going to be less negative in that spot but then as go you farther out from that spot in the membrane, the change in the membrane potential is going to be be less and less. The ligand, the neurotransmitter, is diffusing away over distance so its concentration is less. It's going to be less likely to open sodium channels. So we have sodium rushing in at this spot but the ligand diffuses away so its effect on the membrane potential and decreases as you go farther and farther from that site. What's important to realize about these graded potentials, is that they are going to decay over space (distance) along the membrane, and over time as you've just put a little pulse of that neurotransmitter. When everything's diffuses away then these ion channels close. As we've already mentioned with graded potentials, if you give a greater stimulus, then you're going to have a bigger response. So when you add more neurotransmitters the second time, it's gonna be a stronger stimulus. It's going to open more of these ligand-gated sodium channels, let more sodium in, cause a larger increase in the membrane potential and affect the membrane farther out. That's what we see with this red curve, where we have a bigger response. We'll see why these properties of graded potentials are so important in the nervous system. But in our next session,we'll be talking about a different type of change in the membrane potential which you're probably familiar with, action potentials. To sum up this session, we've talked about the equilibrium potential of a certain ion, which is when the chemical gradient and the electrical gradient oppose each other. We talked about how the resting membrane potential is established. How we need the sodium potassium ATPase to make the gradients of the ions. And that we will have the potassium and sodium leak channels that are also important in establishing where the membrane potential, our resting membrane potential sits. However, if we inactivated the sodium potassium ATPase and let those leak channels open or if we let them continue to function, then eventually we would dissipate the resting membrane potential. It would become zero because we would have no more sodium or potassium gradient without the sodium-potassium ATPase. It's an extremely important molecule in signaling. Then we finished up talking about graded potentials, which vary in size with the strength of the stimulus, and they're going to decay over time and space along the membrane.
