Organic anion transporter 1

Transcription

In the last video on the nephron, we talked about the different parts of the nephron and what, I guess, molecules are reabsorbed by the body and the different parts. If you remember, in the proximal convoluted tubule, we talked about maybe glucose and amino acids and sodium being reabsorbed. We talked about the ascending part of the loop of Henle. We talked about salts, so that sodium, potassium, chlorine being reabsorbed. In the distal convoluted tubule, it was calcium, other things. But at least in my mind, when I first learned it, I said how does that happen? How do we actively pump out these things, especially against their own concentration gradients? What I want to do in this video is get a little bit more depth on exactly what's happening on the borders of these tubules to actually allow these ions to be selectively transported out of the lumen or the inside of these tubes or to be reabsorbed out of the filtrate. The mechanism's actually reasonably similar in the different parts of the nephron, but let's look at each of the parts, because they're each reabsorbing different types of molecules. And I won't go through all of the molecules, but I'll just give you a sense of things. Let's start with the proximal tubule right here. So let's say if we were to zoom in right over on that part-- so let me draw the inside of the nephron. The inside of the nephron maybe looks something like this. So this the inside. This is where our filtrate is right here. Actually, let me draw it a little bit different than that. So the inside, I'm going to draw it like this because the proximal tubule has these little things that stick out, sometimes referred to as a brush border. So this inside right here, this is our lumen. That is where the filtrate is. The glomerular filtrate is coming in this direction. This is, you can imagine, the inside of the nephron. And then the border of the tubule is made up by a bunch of cells. So maybe this is one cell right here, this is another cell right here, that's another cell. Obviously, this is a cross-section. It would be actually more of a cylinder. It would go around like that. This is to give an idea. That's another cell right there. And maybe this is their basal side right there. And when we say basal, we can imagine that's kind of the base of the cell. Those are good words to know, fancy words. So the side of the cells that are facing the lumen, or kind of facing the inside of our tubule, this is called the apical side. And then this side is normally referred to the basal lateral side, or this membrane, if you view this as a membrane, this would be the basolateral membrane. This is true regardless of what part of the nephron we're in, whether the proximal, whether the loop of Henle, or whether we're in the distal part. What we have here, and on the other sides of these cells, we'll have our peritubular capillaries. That's another fancy word. So our peritubular capillaries will look something like this. They're actually cells as well. Actually, instead of drawing the cells, I'll just draw it as kind of the tube of-- I'll just draw it like this. They're porous. So this is actually blood flow right here. This is blood right here. This is blood right here. I'm not going to do too much detail on the actual cells of the capillary walls. I really want to give you the idea of how things are transported out of the lumen, how they're selectively reabsorbed. So this is the peritubular capillary. And once again, fancy word, but peri means around, like perimeter. So it's around the tubes. These capillaries go around the tubes. If I were overlay it on this picture, we have these capillaries that are going all around the tubes. So when things get secreted or reabsorbed out of the nephrons, they're going into those capillaries. So this is our proximal convoluted membrane right here. Let's think about what happens with the glucose. So what happens is we actually have sodium-potassium pumps on the basolateral side of these cells. So this is sodium-potassium pumps. I'll just draw one right here. You might want to watch the video on sodium-potassium pumps. I have a whole video on it. But the idea here is that sodium, maybe I'll draw as plus particles right there, they'll attach on the inside right here, ATP will come along. When ATP attaches to the right part of this protein, it'll change its shape, its conformation, and then the protein will essentially close on this side and open on that side, and then when it's in that conformation, the sodium doesn't want to bond as much to the protein and it will go outside or it'll cross the basolateral membrane and eventually make its way into the blood. And then on the other side, it's a sodium-potassium pump. When it's in this kind of open configuration-- I'll draw it over here; I have a whole video on this-- at that point, potassium likes to bond to it. So potassium likes to bond to it. Maybe it bonds to it over here. This is a gross oversimplification. That causes the protein to change its conformation. It doesn't require ATP at that point, and it goes back to this conformation, and then the potassium doesn't want to bond anymore, and then it gets released, because the protein is now a different shape. So the general idea: Sodium bonds. ATP bonds. The ATP gets its phosphate popped off of it. That changes the shape of the protein to this. Now the sodium wants to get released, and now potassium wants to join. When potassium joins, we get to our original one. The end product of this is we're having sodium being pumped out of the cell and we're having potassium being pumped into the cell, and this is active transport. Why is it active transport? Because we're using ATP to drive sodium against its concentration gradient to keep pumping the sodium out of the cell, and then potassium kind of comes in, you could almost imagine, passively. It doesn't require ATP. And that's why this is often called a sodium-potassium ATPase, which means it's a protein or an enzyme that breaks ATP. But it breaks ATP, it uses that energy to change its shape to pump sodium out and potassium in. Well, anyway, this is all a review of what we learned in those videos, but how does that help us, for example, get glucose out of our lumen? Well, what we have over here is we have other proteins. I'll just do the example of glucose. Let's say we have a protein here. There's a very general term for this. It's a cotransporter or a symporter. Symporter means it transfers two types of molecules in the same direction. Cotransporter means one molecule wants to go through because of its concentration gradient and the other molecule kind of goes along for the ride. So you can imagine, we're actively pumping out sodium. So if we're actively pumping out sodium over here on the basolateral side, then we're going to have a low sodium concentration here. The more we pump out, the lower this is, and eventually it's going to be lower than the sodium concentration in the lumen. So the sodium concentration gradient, if there was no membrane here, sodium would want to go across this to kind of make up for all of the lost sodiums over here. Sodium would want to cross that if there was no barrier. These cells here take advantage of sodium wanting to move down its concentration gradient, which is happening because of this active transport over here, but it uses that energy of sodium going down its concentration gradient to actually also transport, in this case, maybe some glucose. So if you had to visualize it, you could imagine a protein that's on this apical membrane right here. Maybe it looks something like this. This is to get some type of visualization. Maybe you have more sodium on this side than you have on this side, so sodium is more likely to bond here. Maybe glucose will bond here. This is just a simplification, but when they bond, this protein is going to change its shape to look something more like this when they bond, and now the sodium is going to be here and the glucose is going to be here. We're essentially on the inside of the cell now, and in this conformation, they don't want to bond as much to the amino acids or whatever else is in the protein, and then they get released. And when they get released, then the protein will change its shape back to this right here and we can do this cycle over again. But this is all stipulated on the idea that there's more sodium over here to bump into this point to make this reaction happen. So sodium's going to go down in its concentration gradient. It's taking glucose for the ride. And so essentially glucose concentration will go up high here, and then if we make this porous to glucose so glucose can go through, then glucose will eventually, if this gets high enough, it'll just go down its concentration gradient eventually into the blood. And this same exact process is happening, maybe not exactly with glucose, but throughout the entire nephron. If we go to the loop of Henle, if we go to the ascending part right here, where we're trying to get the salts out of the picture, same idea. So let's say that that right there is the lumen. This is a cell that makes up the wall of the lumen. We're in the loop of Henle now and you have a sodium-potassium pump out here. You have sodium being pumped out. You have potassium gets pumped in, but actually, potassium channels are leaky, so potassium can often make its way back out in either direction. So what's happening to potassium isn't that important. But so sodium concentration becomes low here. So what we have are symporters over here, just like we had with glucose, but in this case, sodium wants to enter just as the case with glucose, but here we're trying to transport chlorine and potassium ions. So that's what we're going to join. That's what's going to take advantage of sodium's concentration gradient. We're going to have potassium and we're going to have chlorine ions. And actually, this symporter right here, it's called the sodium-potassium-chlorine cotransporter, and it's actually the second variation that you actually get in the ascending loop of Henle. So eventually, you're going to end up with a lot of chlorine here-- actually, potassium from both directions-- but as long as this is porous to chlorine, if this concentration gets high enough, the chlorine is going to make its way out and help make the medulla that much saltier along with the sodium. Same thing in the distal convoluted tubule. There, calcium. It's a little bit different. So if we're in the distal convoluted tubule, these kind of villi, these things that stick out-- this is only in the proximal convoluted tubule, those brush borders. But over there-- and just so you know, this idea where we're using a concentration gradient that's driven by some type of active transport to transport other things, this is called secondary active transport. That's nice to know. And then just finishing up at the distal convoluted tubule. So this was the lumen. Let's say that this is the lumen right here, so we have cells on either side of that. I think you get the general idea. The distal's a little bit different so let's say this is a cell, and let's say that this is a peritubular capillary right here. This is our blood. What we have here is once again, we're pumping sodium out. Sodium-potassium pumps. I have a whole video on that, and that pumps potassium in, so you end up with a lot of sodiums over here. The apical membrane that faces the lumen, it's porous to calcium. Whatever the concentration of calcium here, it's going to be here. So maybe you have calcium. These are calcium ions just like that floating around. And right here, what you have is an antiporter. So our concentration in the blood of sodium is going to be higher because we keep pumping it out. And so sodium, if you let it go down its concentration gradient, it would go back in. And so maybe right here you have some sodium going down, its concentration gradient going back in, and then when that goes in, that you can almost imagine it's some type of a rotating door, it makes the calcium go out. You can try to visualize it yourself how a protein would actually do that. I kind of imagine a revolving door. The sodium makes the door revolve. The calcium is at the other part of the door and it gets spit out. So this is called an antiporter because they're going in different directions, but once again, it's secondary active transport, because the only way that this could work is if we have active transport using ATP of the sodium out of the basolateral membrane in every one of these cases. Anyway, hopefully, you found that useful. It's more detailed than you normally get on how the nephron is actually pumping things out of the lumen into the peritubular capillaries, but for me, it made things a lot more concrete. It helps me really kind of internalize what the nephron is up to.