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How a sodium potassium pump can maintain a voltage gradient across a cell or neuron's membrane. Created by Sal Khan.
Video transcript
In the last video, I showed you what a neuron looked like and we talked about the different parts of a neuron, and I gave you the general idea what a neuron does. It gets stimulated at the dendrites-- and the stimulation we'll talk about in future videos on what exactly that means-- and that that impulse, that information, that signal gets added up. If there's multiple stimulation points on various dendrites, it gets added up and if it meets some threshold level, it's going to create this action potential or signal that travels across the axon and maybe stimulates other neurons or muscles because these terminal points of the axons might be connected to dendrites of other neurons or to muscle cells or who knows what. But what I want to do in this video is kind of lay the building blocks for exactly what this signal is or how does a neuron actually transmit this information across the axon-- or really, how does it go from the dendrite all the way to the axon? Before I actually even talk about that, we need to kind of lay the ground rules-- or a ground understanding of the actual voltage potential across the membrane of a neuron. And, actually, all cells have some voltage potential difference, but it's especially relevant when we talk about a neuron and its ability to send signals. Let's zoom in on a neuron's cell. I could zoom in on any point on this cell that's not covered by a myelin sheath. I'm going to zoom in on its membrane. So let's say that this is the membrane of the neuron, just like that. That's the membrane. This is outside the neuron or the cell. And then this is inside the neuron or the cell. Now, you have sodium and potassium ions floating around. I'm going to draw sodium like this. Sodium's going to be a circle. So that's sodium and their positively charged ions have a plus one charge and then potassium, I'll draw them as little triangles. So let's say that's potassium-- symbol for potassium is K. It's also positively charged. And you have them just lying around. Let's say we start off both inside and outside of the cell. They're all positively charged. Sodium inside, some sodium outside. Now it turns out that cells have more positive charge outside of their membranes than inside of their membranes. So there's actually a potential difference that if the membrane wasn't there, negative charges would want to escape or positive charges or positive ions would want to get in. The outside ends up being more positive, and we're going to talk about why. So this is an electrical potential gradient, right? If this is less positive than that-- if I have a positive charge here, it's going to want to go to the less positive side. It's going to want to go away from the other positive charges. It's repelled by the other positive charges. Likewise, if I had a negative charge here, it'd want to go the other side-- or a positive charge, I guess, would be happier being here than over here. But the question is, how does that happen? Because left to their own devices, the charges would disperse so you wouldn't have this potential gradient. Somehow we have to put energy into the system in order to produce this state where we have more positive on the charge of the outside than we do on the inside. And that's done by sodium potassium pumps. I'm going to draw then a certain way. This is obviously not how the protein actually looks, but it'll give you a sense of how it actually pumps things out. I'll draw that side of the protein. Maybe it looks like this and you'll have a sense of why I drew it like this. So that side of the protein or the enzyme-- and then the other side, I'll draw it like this. It looks something like this, and of course the real protein doesn't look like this. You've seen me show you what proteins really look like. They look like big clusters of things, hugely complex. Different parts of the proteins can bond to different things and when things bond to proteins, they change shape. But I'm doing a very simple diagram here and what I want to show you is, this is our sodium potassium pump in its inactivated state. And what happens in this situation is that we have these nice places where our sodium can bind to. So in this situation, sodium can bind to these locations on our enzyme or on our protein. And if we just had the sodiums bind and we didn't have any energy going into the system, nothing would happen. It would just stay in this situation. The actual protein might look like something crazy. The actual protein might be this big cloud of protein and then your sodiums bond there, there, and there. Maybe it's inside the protein somehow, but still, nothing's going to happen just when the sodium bonds on this side of the protein. In order for it to do anything, in order for it to pump anything out, it uses the energy from ATP. So we had all those videos on respiration and I told you that ATP was the currency of energy in the cell-- well, this is something useful for ATP to do. ATP-- that's adenosine triphosphate-- it might go to some other part of our enzyme, but in this diagram maybe it goes to this part of the enzyme. And this enzyme, it's a type of ATPase. When I say ATPase, it breaks off a phosphate from the ATP-- and that's just by virtue of its shape. It's able to plunk it off. When it plunks off the phosphate, it changes shape. So step one, we have sodium ions-- and actually, let's keep count of them. We have three sodium-- these are the actual ratios-- three sodium ions from inside the cell or the neuron. They bond to pump, which is really a protein that crosses our membrane. Now, step two, we have also ATP. ATP gets broken into ATP plus phosphate on the actual protein and that changes the shape. So that also provides energy to change pump's shape. Now this is when the pump was before. Now after, our pump might look something like this. Let me clear out some space right here. I'll draw the after pump right there. And so this is before. After the phosphate gets split off of the ATP, it might look something like this. Instead of being in that configuration, it opens in the other direction. So now it might look something like this. And of course it's carrying these phosphate groups. They have a positive charge. It's open like this. This side now looks like this. So now the phosphates are released to the outside. So they've been pumped to the outside. Remember, this is required energy because it's going against the natural gradient. You're taking positive charge and you're pushing them to an environment that is even more positive and you're also taking it to an environment where there's already a lot of sodium, and you're putting more sodium there. So you're going against the charge gradient and you're going against the sodium gradient. But now-- I guess we call it step three-- the sodium gets released outside the cell. And when this changes shape, it's not so good at bonding with the sodium anymore. So maybe these can become a little bit different too, so that the sodium can't even bond in this configuration now that the protein has changed shape due to the ATP. So step three, the three Na plusses, sodium ions-- are released outside. Now once it's in this configuration, we have all these positive ions out here. These positive ions want to get really as far away from each other as possible. They'd actually probably be attracted to the cell itself because the cell is less positive on the inside. So these positive ions-- and in particular, the potassium-- can bond this side of the protein when it's in this-- I guess we could call it this activated configuration. So now, I guess we could call it step four. We have two sodium ions bond to-- I guess we could call it the activated pump-- or changed pump. Or maybe we could say it's in its open form. So they come here and when they bond, it re-changes the shape of this protein back to this shape, back to that open shape. Now when it goes back to the open shape, these guys aren't here anymore, but we have these two guys sitting here and in this shape right here, all of a sudden these divots-- maybe they're not divots. They're actually things in this big cluster of protein. They're not as good at staying bonded or holding onto these sodiums so these sodiums get released into the cell. So step five, the pump-- this changes shape of pump. So pump changes shape to original. And then once we're in the original, those two sodium ions released inside the cell. We're going to see in the next few videos why it's useful to have those sodium ions on the inside. You might say, well, why don't we just keep pumping things on the outside in order to have a potential difference? But we'll see these sodium ions are actually also very useful. So what's the net effect that's going on? We end up with a lot more sodium ions on the outside and we end up with more potassium ions on the inside, but I told you that the inside is less positive than the outside. But these are both positive. I don't care if I have more potassium or sodium, but if you paid attention to the ratios I talked about, every time we use an ATP, we're pumping out three sodiums and we're only pumping in two potassiums, right? We pumped out three sodiums and two potassiums. Each of them have a plus-1 charge, but every time we do this, we're adding a net-1 charge to the outside, right? 3 on the outside, 2 to the inside. We have a net-1 charge-- we have a plus-1 to the outside. So we're making the outside more positive, especially relative to the inside. And this is what creates that potential difference. If you actually took a voltmeter-- a voltmeter measures electrical potential difference-- and you took the voltage difference between that point and this point-- or more specifically, between this point and that point, if you were to subtract the voltage here from the voltage there, you will get -70 millivolts, which is generally considered the resting voltage difference, the potential difference across the membrane of a neuron when it's in its resting state. So in this video, I kind of laid out the foundation of why and how a cell using ATP, using energy, is able to maintain a potential difference across its membrane where the outside is slightly more positive than the inside. So we actually have a negative potential difference if we're comparing the inside to the outside. Positive charge would want to move in if they were allowed to, and negative charge would want to move out if it was allowed to. Now there might be one last question. You might say, well, if we just kept adding charge out here, our voltage difference would get really negative. This would be much more negative than the outside. Why does it stabilize at -70? To answer that question-- these are going to come into play in a lot more detail in future videos-- you also have channels, which are really protein structures that in their open position will allow sodium to go through them. And there are also channels that are in their open position, would allow potassium to go through them. I'm drawing it in their closed position. And we're going to talk in the next video about what happens when they open. But in their closed position, they're still a little bit leaky. And if, say, the concentration of potassium becomes too high down here-- and too high meaning when they start to reach this threshold of -70 millivolts-- or even better, when the sodium gets too high out there, a few of them will start to leak down. When the concentration gets really high and this is really positive just because of the electrical potential, some of them will just be shoved through. So it'll keep us right around -70 millivolts. And if we go below, maybe some of the potassium gets leaked through the other way. So even though when these are shut-- if it becomes too ridiculous-- if it goes to -80 millivolts or -90 millivolts, all of a sudden, there'd be a huge incentive for some of this stuff to leak through their respective channels. So that's what allows us to stay at that stable voltage potential. In the next video, we're going to see what happens to this voltage potential when the neuron is actually stimulated.