So we're going to move right along today and talk about the next chapter, chapter 12. This chapter focuses on transport across the membrane. First, we're going to talk about the importance of ions, because as much as what we talk about today is going to focus on membrane transport in general, it's no secret, and it'll become clear after today's lecture, that most transport across the membrane is the transport of ions. And in fact, the transport of ions is probably the most important.
Of all the membrane transport that a cell does. So again, all the concepts that we discussed today will be applicable to transport across the membrane of any molecule. But since most of that transport is based in ions, that's really where we focus our lecture.
So we'll start off the lecture by talking about the importance of ions, and then of course a little bit of the basics of ion transport. In that conversation, we will need to discuss and define channel proteins and transporter proteins. More specifically, the class or subclass of transporter proteins called the pumps.
It'll be clear what these are once we get to them, but for now it suffices to say that these are some of the ways and some of the proteins which are responsible for ion transport. We'll use one super important protein as our example. The sodium-potassium pump is a protein, a transporter protein, which pumps, quite obviously, sodium ions and potassium ions. We'll talk about why that's important and how this pump works. We'll discuss the concept of the membrane potential and talk about why and how ions play such a critical role in not only transport across the cell membrane, but maintaining a sort of stored energy, a cellular battery, by the use of ions.
And finally, we'll wrap up with the idea of ion channels. So, this is a logical progression from the last lecture. The last lecture we got a very good understanding, I hope, of the cell membrane, its structure, what it's made of, what it allows and what it doesn't.
And now it's time to discuss how we actually get molecules across this semi-permeable barrier. Cells are not closed systems. Cells are living entities which are in a constant state of flux or molecular communication with their environment. So cells survive pretty much solely by exchanging molecules with that environment that they're in.
This is a two-way exchange. The cell takes things... in from the outside environment, the cell releases things from its interior into the outside environment.
And without this two-way exchange, life simply couldn't exist. But we have this problem. The interior of the lipid bilayer, remember those tails, those hydrocarbon tails, those hydrophobic kinked tails of the phospholipids?
They are hydrophobic, water-repelling. So the interior of the lipid bilayer is hydrophobic. But the molecules responsible and needed for life are almost all hydrophilic. They're polar and or charged. And so we need to get these hydrophilic molecules across this hydrophobic membrane.
And unfortunately the membrane made up of the way that it is just of phospholipids blocks these hydrophilic molecules from passing across it. But we need a two-way exchange. If most of the molecules necessary for life are hydrophilic, and we have this impenetrable hydrophobic wall separating the cell from the outside, we have to have some way of getting these molecules across the membrane.
Some of the hydrophilic molecules responsible for life, sugars, our source of energy, amino acids, our building blocks of proteins, ions, which will become clear. These are typically things we bring into the cell, but don't forget, we've got a lot of crap we've got to get out of the cell, too. Like any living system, cells create metabolic wastes, wastes that could be toxic to the cell if they're allowed to build up.
Those wastes need to be released out of the cell. So again, this two-way exchange. We need to be able to get things in and get things out of the cell. So how do we fix this?
How do we create a transport across a membrane? that inherently blocks the most important molecules responsible for life. Well to do this, to bypass this limitation, we have proteins. Specifically, we have integral transmembrane proteins, and you should know what those terms mean now after the last lecture, that are more specifically transport proteins. Proteins whose sole responsibility it is to get things in and or out of the cell.
So this is the scenario we would be faced with with just a lipid bilayer. We've got some polar charged hydrophilic things in the cell. They can't get out because they can't cross the lipid bilayer. We've got a whole bunch of stuff outside the cell, which is hydrophilic.
We'd like to get that in. They can't get in. They can't get through the lipid bilayer.
So we have these unique, specific transport proteins. These doorways, protein doorways in the lipid bilayer that let these purple triangles out. of the cell.
Notice this protein complex here is only for purple triangles. It is the doorway for purple triangles to leave the cell. It allows these green rectangles into the cell from outside.
Need a separate transport protein for that, but that's okay. And then some transport proteins are a two-way door and can let blue circles in or out of the cell depending on what the cell needs at that time. So these transport proteins provide specialized custom doorways through the cell membrane for specific types of molecules or even in the most extreme case for only one specific type of molecule. But those are the two concepts we need to carry forward for this lecture.
Transport proteins are doorways for molecules to leave and enter the cell. However, they are specialized doorways only for a subset of particular molecules. In addition, it makes sense that the cell wants some control over this. Sometimes you'd like purple triangles to leave, sometimes you'd rather they didn't. And so this transport is regulated.
These doorways can typically be opened or closed, allowing molecules to move across the membrane or not. So that's what we're going to talk about today. Transport across the cell membrane in general and where appropriate in specifics too.
But before we go there, we're going to be throwing around a lot of terms today, terms that are specific to transport across membranes. So Let's be clear what we mean by some of these terms before we move forward. First, we've already introduced it, but we have this idea of transporter proteins. A transporter is a protein that contains moving parts and can transfer molecules from one side of the membrane to the other.
The way that transporter proteins work is by changing their shape. That should be a very familiar concept by now. Most proteins accomplish their activities, accomplish their functions by shape changes. And transporter proteins are no different. What transporter proteins do is they take a molecule from one side of the membrane, change their shape, and squeeze that molecule out to the other side.
And so transporter proteins can typically move molecules from inside the cell to out, or from outside the cell to in. The exception to that is it is extremely rare for a transport protein to move molecules in both directions at the same time. We're going to see an example later on in the lecture of how a transport protein can move molecules either from in to out or out to in.
But what's important is that it's not done at the same time. The cell never wastes its energy and wastes its own time. So it would make no sense to move, say, glucose out of the cell, only to turn right around and move it right back in.
Because it started in the cell. Why would you do that? But there are times where the cell will, at this point in time, move all the glucose out. And later on as conditions change, that same transporter protein will move glucose in.
Okay, so transporter proteins can do both, they just typically don't do both at the same time. The other thing transporter proteins can do is that they can oftentimes move things, move molecules against their concentration gradients. We're going to talk quite a bit more about that as we get deeper on into the lecture.
This is contrasted to another family of proteins called channel proteins. Channel proteins are also doorways in the membrane. But they typically have no moving parts whatsoever. They're often referred to as pore proteins.
You can think of a pore as just a hole or an opening. And that's exactly what channels do. They create small holes in the membrane.
These small holes are hydrophilic, so they are acceptable and favorable to hydrophilic molecules going through them. But they are selective in the sense that not any hydrophilic molecule can move through any channel. There are specific channels for specific molecules. Most channels are specific for ions and more particularly small, inorganic, which is just a fancy way of saying carbon lacking ions, and so most channels are referred to as ion channels because that's what they allow through.
For channels there is no active transport. Always, when dealing with a channel, molecules are following their concentration gradients, moving from areas where they are more concentrated to less crowded areas where their concentration is lower. So, this is our first figure from your textbook. It kind of shows the difference between these two categories. Channel proteins first because they're simpler.
Here it is, a hole in your membrane, a hydrophilic channel, a hydrophilic pore embedded in the membrane where ions can pass through, typically going from where there's more of them to where there's less. Transporter proteins on the other hand, moving parts. You can see how this transporter protein started.
closed here at the top region and open in the bottom. In comes a molecule into the open side. The binding of that molecule causes a shape change.
You can imagine, I hope, that this molecule kind of snaps where the bottom comes together opening the top. These two halves kind of rotate towards each other. Bottom is closed, top is open, and there goes your molecule out the other side transported across the membrane.
So back to the idea of ions, more specifically ion concentrations, concentration gradients and all of that. I've already said it in the opening slides but much of the transport across membranes is dedicated in general to ion transport. Ions are the most critical molecules for a cell to consider around its membrane and the most critical molecules to be transported. So in many ways the transport of ions is the most critical of all the cellular membrane transport mechanisms.
For that reason, we focus on ion transport more than any other in today's lecture. Cells intentionally maintain differential ion concentrations between the inside of the cell and the outside. So oftentimes you'll see the concentration of inorganic small ions differing sharply on either side of the membrane. And these differences are intentional, they're on purpose, and they are crucial for cellular survival.
We'll see this near the end of the lecture. Some examples of the most critically controlled ions, which cells manipulate the movement of and regulate, are sodium ions, potassium ions, calcium ions, chloride ions, and protons. So this figure here, not from your text, just shows in general what we mean by this. On some sides of the membrane we have more sodium, on other...
On the other side of the membrane we have more potassium, we see more chloride over here, more of these non-labelled negatively charged ions over here. And so we have this sharp divide, this sharp difference in the ions that we find inside a cell versus the ions that we find outside of the cell. And the cell does that on purpose. It's controlling the concentration of these ions, keeping them more concentrated on one side or the other.
These ions, it should go without saying, are the most plentiful ions in life, the most plentiful ions in a cell's environment. Sodium, potassium, calcium, chlorine, and protons are the most abundantly found ions that we see. And again, their movement, the regulation of their transport, is critical for cellular survival. It's important to note here, and only here, as we go through this lecture, remember that ion transport is the fundamental basis of neuronal communication and neuronal activity.
Neurons function, the brain functions, you can almost say exclusively due to the transport of sodium and potassium. So a lot of the concepts we're going to skirt around today are the underlying concepts for all of neuroscience. But intentionally, I am not going to go into any cellular-specific activity here.
We won't be talking about neurons and specifics, nor will we be talking about any other cell type and specifics, just because this is a cell biology course. We're supposed to be covering the basics here. So the material that I cover in this lecture is applicable to all cells, and that's intentional.
But if you're interested in neuroscience, if you've had neuroscience training in the past, if you think you're going to have neuroscience training in the future, these concepts we're covering in these lectures are fundamental to those ideas of neurons and information transfer. within and between neuronal cells. But back to the general. So, sodium is the most plentiful ion that we find outside of a cell relative to its interior. So the cell intentionally keeps the amounts of sodium inside the cell much, much lower than the amount of sodium that you would find outside the cell.
The pattern for potassium ions is the opposite. Potassium is the most plentiful ion that we find inside cells, and it is much more concentrated inside the cell than it would naturally be found outside the cell. A mnemonic to remember this, because I have a horrible memory, is the word kin.
Hopefully you're familiar with the word kin. It means family member or relative, kinfolk. If you can remember the word kin, you can remember this concept K for potassium, IN for in.
So potassium is much more concentrated in the cell. K-I-N, kin. This table here from your textbook, table 12-1, shows the relative abundance or concentration of all of the ions that we talked about in the previous slide. And you can see what I've just mentioned is here on the table.
Potassium, I'm sorry, sodium is much more concentrated outside the cell relative to inside, intracellular. Sodium levels are much lower. Potassium has the opposite pattern, almost exactly opposite if you compare the numbers. Potassium is much more concentrated inside the cell relative to outside.
Magnesium is fairly well balanced. Calcium much more concentrated outside the cell than inside. Protons roughly balanced. Makes sense, don't forget! Protons contribute to pH. Proton concentration gets too high, you have a low acidic pH. Proton concentration gets too low.
And you have a very basic alkali pH. So it makes sense that we're hovering around neutral here on either side of the membrane, but there are differences in concentration. And chlorine, chlorine much, much more concentrated outside of the cell versus inside, chloride ion I should say. All of this is on purpose, all of this is kind of a finely balanced choreographed balance, again for lack of a better word, of charge and concentration.
If the electrical charge balance, that is the overall net electrical charge, were too skewed. In other words, if we were much, much more positive inside the cell than we were negative, those electrical or ionic forces would just tear the cell membrane apart. You would have too much electricity, for lack of a better way of saying it, going around within the cell.
So it's critically important for the cell to keep the overall charge balanced. It's going to have a hell of a lot of... potassium inside the cell, you better have a hell of a lot of negatively charged stuff, too, to get the overall charge inside the cell neutral.
Same goes for sodium outside the cell. If you're going to have a hell of a lot of sodium outside the cell, sodium is positively charged. You better have a lot of stuff out there that's negatively charged, too, to keep the overall charge outside the cell neutral. Inside the cell, all the intracellular positively charged potassium is balanced by a very large, wide array of negatively charged anions.
And there's so many different types of them that they're not included on this table. If you read the fine print here, that's what the fine print here says, that all of the potassium inside the cell has to be balanced, and it's balanced by a collection of different negatively charged anions, such as bicarbonate, potassium ion. Proteins and nucleic acids themselves, as we know, are negatively charged, at least sometimes for proteins, all the time for nucleic acids, and all of these things help to balance the positive charge of potassium. We need this balance outside the cell, too.
We also need an electrically neutral environment outside the cell. There's a hell of a lot of sodium outside the cell, but there are almost equal amounts of chloride ion, and those two balance one another quite effectively. So, chlorine ion is the most...
Common way to balance the potassium charge outside of the cell. That's not to say the overall net charge is always zero. There are minor and localized imbalances of electric charge typically found right at the cell membrane, and that's on purpose. Actually, it is those minor, rare, localized events of charge imbalance that are the most critical for cellular survival, and we'll see that near the end of the lecture too.
So the cell goes through a great, great... amount of activity and a great amount of effort to make sure that charges in general are balanced, but conversely the cell also intentionally makes charge imbalanced right near the membrane in order to harness some of the energy associated with that. And so these are also important things for the cell to control, to balance, to regulate, to monitor, and transport proteins and transport across the membrane is an underpinning phenomenon for all of that.
So let's kind of start over now in a way and go back to some of our knowledge about lipid bilayers and talk about why transport is blocked, how transport is achieved and work our way back to this idea of the importance of charge, charge balance and imbalance. I'm sure you've put it together yourself already but it's worth saying explicitly, ions are charged. Ions are some of the most hydrophilic molecules we have.
They are very water loving and because they are so extremely hydrophilic they cannot, literally can't, get through the hydrophobic lipid bilayer because there's too much chemical differences between the hydrophobic tails of the bilayer and the hydrophilicness of the ions. So the segregation of ions, keeping ions on either side of the cell membrane, is controlled by the bilayer itself. The simple fact that ions can't diffuse across the cell membrane means that ions stay where they're supposed to.
If we're going to move ions, we have to do it intentionally, so that means the movement of ions requires or needs transporter proteins and channel proteins. This gives the cell the ability to control that movement because it is the cell that regulates the manufacture, the synthesis, and the state. of the transporter of channels.
If you don't want sodium to flow across the membrane anymore, close your sodium channel. Sodium can't diffuse across the bilayer itself, and if the channel for sodium is also closed, sodium will not be moving across your cell membrane. If you've reached the point as a cell where you do want sodium to move, open the channel.
Sodium still can't diffuse across the bilayer itself, but with the channel open, sodium can move through that portal, that pore, and go to the other side of the membrane. So we have charged molecules being the most hydrophilic, they're strongly repelled by the hydrophobic interior of the cell membrane. Most of the time, given enough time, all molecules will diffuse across everything and anything.
The question becomes, how quickly do molecules diffuse across the membrane, depending on what type of molecule it is, and then related to that, is that natural diffusion time fast enough to support life? In other words, if a sodium molecule single sodium molecule is going to diffuse across a lipid bilayer once every five years or so. Is that fast enough to support life?
Now, the obvious answer is no, but for other molecules that aren't quite as hydrophilic as ions, maybe the speed of diffusion across the membrane itself is enough. So small, nonpolar. Okay, so these are non-water loving. Small nonpolar molecules, and some examples are oxygen and carbon dioxide, the cell membrane doesn't even exist to them. They're small, so they move around easily.
They're nonpolar, so they don't mind the hydrophobic environment of the cell membrane. They easily diffuse across the cell membrane all by themselves. They don't need channels, they don't need transporters, they don't need any proteins.
They float through the cell membrane like a ghost through a wall. So we don't need to worry about these molecules. They're going to flow just fine on their own.
We also have small polar molecules that are uncharged. Now that's critical. They're polar, so hopefully you remember from early on in the lecture, hydrogen bonds, polar bonds, water being a polar molecule, partial charges and all that.
Molecules that have that type of polarity have hydrogen bonds and partial charges, but aren't fully charged. As long as they're small, they can also diffuse across the membrane. Here size matters.
The lack of charge is important, but the fact that these molecules are small means that they can slip through the cracks, so to speak, of the cell membrane, and they can get across the cell membrane without any channels or transporters. Water is a good example of a molecule that can do this. So can ethanol explain some of the potent effects of ethanol when it's consumed? It just diffuses into cells, all cells. Glycerol can also do this.
How about uncharged polar molecules that ain't so small? Well, some examples of these are amino acids, sugars, nucleosides. These are the bases that make up DNA along with the riboses.
They lack the phosphates. They lack the charge of nucleotides. So they are bases in ribose sugars with no full charge.
What do these molecules do? Well, oops, got ahead of myself there. Sorry about that. Well, they can't diffuse across so easily because they're too big.
Now the combination of being polar, having partial charges and being big makes it difficult to diffuse across the membrane. Can they diffuse across the membrane on their own? Yeah, they can, but they can't do it fast enough to support life.
So things like amino acids, glucose, nucleosides and other related molecules, they do require transporters or channels because the speed at which they diffuse across the membrane just isn't fast enough for the speed that the cells need. And finally, although we already said it, ions. Polar and charged molecules containing full charge are all but blocked from diffusion across the membrane, no matter how big or small they might be.
Do they diffuse? Yes, they do. What are the speeds of diffusion?
Literally, on the order of months to years. So if you have to wait months for a single sodium ion to cross the lipid bilayer of the cell, that is much too long to support life, and so they require channels. and transporters.
It's not so much the size of these molecules that hinder their diffusion as it was for these yellow non-charged molecules. It is their full charge. They are simply too charged. They are simply too hydrophilic. They love water too much, and so they can't sneak through the hydrophobic tails of the lipids.
Believe it or not, even though water is itself polar, water has partial charge. There's nothing more hydrophilic than water, in a way of speaking. Hydrophilic means water-loving, and water certainly loves itself. Still, lipid bilayers are a billion times more permeable to water. That means a billion times more likely to let water float through than they are to allow the smallest of ions to diffuse across their membrane.
Smallest of ions, for example, sodium. A billion times! That's ten to the ninth power. It's 10 to the 9th power more likely that water, itself hydrophilic, will diffuse across a lipid bilayer than an even smaller inorganic ion such as sodium. That's the effect of full charge.
And so full circle now, this means we need specific dedicated proteins to facilitate transport across the membrane. If a cell is going to move ions such as sodium, potassium, calcium in and out of their cell, if the cell is going to move... Large, non-charged polar molecules such as glucose, amino acids, nucleosides, in and out of the cell, they can't rely on diffusion.
Diffusion for these molecules is much too slow. Here is where we need our membrane transport proteins. Transport proteins are found in all membranes, in all cells throughout life. You cannot be a living cell without transport proteins.
Each membrane is specialized. with the transport proteins it contains because each transport protein is specialized for the types of molecules it will allow through. For example, a sodium transport protein will not allow potassium through it.
Even though sodium and potassium are roughly the same size and have the same charge, these channels and transporters are highly specialized and only allow their own particular molecules through them. We call this being exclusive. Transport proteins are exclusive, just like an exclusive club that will only let in the people who are on the list at the front door.
It won't allow anyone else in. You have to be a member of the club to get in, and the same is true for the channels. The types of transport proteins that we deal with are transporters and channels.
We've talked about that before. Channels rely specifically on the charge of the molecule and the size of the molecule to determine whether or not that molecule will be let through. And so the exclusivity of channels is due to the size and charge of the molecule going through it.
Okay, that's how channels work. Molecules that are the right size and charge pass through the channel. They float right through it, no problem.
It's almost as if the channel is a trapdoor and the molecule just flows right through it. Molecules with the wrong size and or the wrong charge don't fit through the trapdoor, don't get through the channel. Transporters are a little bit different. Transporters are a little bit more specific. To pass through a transporter protein, the molecule has to fit perfectly into a binding site which is on the transporter, like a key into a lock.
It's not just a simple matter of right size, right charge. It is the complete three-dimensional shape of the molecule to be transported which must fit perfectly into a binding site on the transporter. The transporter, only with a perfect lock and key fit, only with the correct molecule bound to it, will change its shape, squeezing that molecule across the bilayer.
We saw this diagram before, but it is correct in its schematic. You can see here that the solute has a particular shape to it, and that shape fits perfectly into a mirror image shape on the transporter protein. The solute binds to the transporter protein, and that...
Binding is the signal for this protein to snap shut on top and snap open on the bottom, allowing the molecule through. So transport proteins can be thought of much more as a turnstile than a trapdoor. Moving parts, getting in, being validated, being allowed through. Perfect image here for us, right? Nice little T station.
So perfect example, perfect analogy for a transporter protein. It is a turnstile. You will.
approach the gate, the gate is closed. You are not allowed through. You feed your Charlie Pass into the turnstile.
It is validated by the turnstile. You fit into the turnstile correctly, and what happens? The doors open, and you're allowed through.
There's a change in shape. There's a movement, and you're allowed to pass through. If you put in the wrong card, let's say you put in a MetroCard from New York City, that's the wrong card. You have not been validated and the door remains closed because you are not carrying the correct information in order to be allowed through this transport protein.
These two different transport proteins, by that I mean transporters and channels, also differ in their energy requirements. It's intuitive I think but channels have no moving parts. Channels are doorways, channels are trap doors, they sit there and so that doesn't take any energy.
You're either open and everyone goes through or you're closed. and no one goes through. So they're largely energy neutral.
But transporters have moving parts. Transporters are snapping open, snapping closed, snapping open, snapping closed, and so movement usually requires energy and certainly transporters are no exception to that. I'm working on the assumption that everyone in class knows the difference between passive diffusion and active transport. We will cover it briefly here, but if these concepts aren't familiar to you, please come to me and get these straightened out for yourself.
Really, everything we're going to talk about from this point moving forward is reliant on this idea of concentration gradients, transporters, active transport, passive transport, etc. So if that's not something you're comfortable with, you should come see me to get it straightened out and then maybe revisit this portion of the lecture. But, in a nutshell, molecules typically have a concentration gradient.
This means they are more concentrated on one side of a barrier than the other. Molecules, like people, tend to move from areas of high concentration to low. If you've got 70 people stuffed into a room that fits 20, it gets hot, it gets sweaty, it gets uncomfortable, and everyone wants to leave. You want to get into the hallway where 5 people are sitting, where the air is fresher, there's more elbow room, and less crowdedness. People prefer to get from regions where they're more crowded to where they're less in molecules.
are the exact same way, they behave the exact same way. So molecules have a natural tendency to flow or move from where they are more concentrated to where they are less. And indeed, diffusion is the process, or the concept, of molecules flowing from high concentration to low. We typically say a molecule followed its concentration gradient when it goes from high regions to low. So on this diagram, all of the molecules shown have the same concentration gradient.
There's a higher concentration on the top than on the bottom. And these molecules want to flow from the top where they're crowded to the bottom where they're not. Simple diffusion, or just diffusion is typically how we refer to it, has this little red dot moving from area of high concentration to area of low. And it's going right through the cell membrane to do that. So you can think of this as oxygen or carbon dioxide can do that.
Passive transport also referred to as facilitated diffusion, is the idea of a molecule still following its concentration gradient from areas of high concentration to areas of low. So that's why we still have the word diffusion in here. However, this molecule cannot go across the cell membrane on its own. The lipid bilayer is blocking its movement, and so a channel is there to allow it.
That's why we call it facilitated diffusion. Is it diffusion? Sure is. Molecule is going from high concentration to low.
The reason why it's facilitated diffusion is because that diffusion had to be facilitated. What's doing the facilitation? The channel. The channel's providing a point of entry where the molecule can follow its natural concentration gradient.
Transporters can do this too. Here the molecule is going from a region of high concentration to low. That's still diffusion.
That's still diffusion. but it needs to go through the transporter to do it. So it's facilitated diffusion. This is contrasted.
So for facilitated diffusion, also referred to as passive transport, molecules are following their concentration gradient. They're going from high to low, but they need a protein to go through in order to cross the bilayer. This is to be contrasted against active transport.
Active transport is moving a molecule against its concentration gradient. Here's the green square, and we are moving the green square from a region where it is less concentrated to more. That's getting one of the people in the nice, breezy, cool hallway and stuffing them back into the crowded room with 70 people. That's going to take energy.
That's not the natural flow. This is not where the molecule wants to go. So the molecule is being forced against its natural tendency to go from a region of low concentration to high concentration. That is called... active transport because it's an active process and it is energy requiring.
Sometimes this energy comes from ATP, sometimes from other sources, we'll discuss that in just a second, but always active transport requires energy. Only specialized transporters can do active transport, and we typically refer to them as pumps because in fact that's what pumps do, isn't it? When you pump water out of a basement or out of a boat, you're taking 70 gallons of water from the boat, and putting it into a million gallons of water in the ocean. That is against the concentration gradient.
The water wants to come from the ocean into the boat. The water wants to go from higher concentration to lower concentration. That is its natural tendency. When you pump water back out of the boat, you're pumping it against its gradient.
That takes energy. That needs a pump. And it's the same for proteins. Protein pumps move things against their concentration gradients.
Protein pumps... are responsible for active transport. Here is the sodium potassium pump.
We'll come back to this guy in just a minute, but just take a look at what it's doing. It is moving potassium from outside the cell to inside the cell. Remember Kin? Potassium is higher in its concentration inside the cell, and this protein is moving potassium from outside, where it is less concentrated, to inside, where it is more.
That is pumping. That takes energy. The sodium-potassium pump pumps sodium from inside the cell to outside, from where it's less concentrated to where it's more. That requires energy. That's going against the concentration gradient.
That is active transport. So, let's try now to get a better and deeper understanding of how channels, transporters, and pumps are different from one another and how they actually achieve their functions. More importantly, building off of the concepts from the last lecture, How channels, transporters, and pumps achieve their functions in the context of the lipid bilayer and the ions that surround it.
So we're going to start with transporters and their functions. So we can get stuff into a cell. That's great. Congratulations. But that's just step one.
You remember the cell we talked about before the exam? All those organelles, all that compartmentalization, all the different stuff happening in different places? Each organelle has its own function. Each organelle has its own job.
Each organelle needs its own stuff. And so each organelle has its own set. of organelle membrane transport proteins which are used to move molecules, the correct molecules, into the correct organelles. So sure, we've got nucleotide transporters on the cell membrane, sugar transporters, amino acid transporters, we've got sodium pumps. Great!
But that just gets this stuff into the cell. Different components need to get to different organelles. The lysosome, for example, has a proton transporter. Why do you think that is?
Why do you think the lysosome? has a proton transporter? Well, your stomach has an acidic pH, right?
The acidic pH of your stomach aids in digestion. The lysosome is the stomach of the cell, quite literally. And so the lysosome also needs an acidic pH to do cellular digestion.
What is acidic? Well, high proton concentrations. How do you get the interior of the lysosome acidic? Well, I guess you need to pump protons into it. Increase the proton concentration inside the lysosome, have it.
give it a low pH, make it acidic, make it digestive. So proton pumps are found on the lysosome membrane, keeping protons in the lysosome, keeping the lysosome acidic. Pyruvate is the name of the sugar metabolite that is converted directly into ATP by the mitochondria.
So, no big surprise that the mitochondrial membrane has a pyruvate transporter on it. Pyruvate's made in the cytosol, in the cytoplasm. Once that pyruvate is made, it needs to be put into the mitochondria so that metabolism can continue.
And the mitochondria has a pyruvate transporter. Hopefully you get the idea. I alluded to this in the last lecture, but the makeup of the membrane of the cell and the organelles gives you a very clear idea of that structure's function.
If I gave you a random membrane and it was studded with proton transporters, you could tell me with some degree of certainty, I think this is a lysosomal membrane, because there's no other organelle in a cell that would require as many proton transporters as this. If I gave you a different membrane, and it was studded with pyruvate transporters, you could ascertain with some degree of certainty, this is probably a mitochondrial membrane, because only the mitochondria needs to pump pyruvate into it. And so the makeup of the proteins in the membranes give you a very clear idea of the function of those structures. because they tell you what those structures needed to pump in and what they needed to pump out. Some transporters, and I mentioned this earlier as well, some transporters, the glucose transporter is a good example, can and will move molecules in either direction, either from in the cell to out or out the cell to in.
They just can't do it at the same time. Right after you've eaten a meal, there's glucose in your bloodstream because you've consumed that food. That means the glucose concentration is higher in the blood than in the cell and so the glucose follows its concentration gradient.
The glucose transporter is a passive transporter. It allows glucose to follow its own concentration gradient. After a meal, glucose moves through the transporter from the blood into the cell. However, after it's been a while since a meal, there's been some fasting, it's been some time since you've eaten, there's a higher level of glucose in the cell from glucose stores.
than there are in the blood. And so the glucose transporter just does what it does, allows glucose to travel along its concentration gradient, this time from the region of higher concentration in the cell to region of lower concentration in the blood. And so glucose leaves the cell through the glucose transporter. This is good for us because the only energy source that our brain can use to survive is glucose.
The brain can't survive on anything but glucose. And so if glucose levels are low in the brain, and in the blood, excuse me, that means the brain is starving. As these glucose stores are released by cells back into the bloodstream, that glucose can go to the brain and fuel the brain for survival.
Cells themselves can live on other things in the short term. They don't need glucose to survive. And so the glucose transporter is truly a turnstile, truly a specialized, exclusive doorway for glucose, but that allows glucose to follow its concentration gradient. Kind of like a turnstile or a gate before and after the game. So, great Boston Bruins game, playing the Montreal Canadiens, everybody wants to go see, big crowds, sold out arena.
Before the game, what is the net flow of human beings? From the street into the arena, everyone is going into the arena. After a meal, glucose, like the people, are all amassed in the bloodstream.
Everyone goes into the cells, going from where the people are most crowded out on the street to where they're least crowded in the arena. Game goes on, it's been a long time since you've eaten, game is over, brain is starving for food, what happens? Well, now everyone leaves the arena, everyone goes in the same direction, just the opposite direction as last time. The glucose leaves the cells and mass back into the bloodstream, the people leave the arena, go back onto the street, everyone moving in the opposite direction.
So the direction of movement in these cases is always governed by the gradient. From... areas of higher concentration to areas of lower. Nice little story for glucose, but it's not so simple for charge molecules. In the localized region of the cell membrane, there are differences in charge between the inside and the outside of the cell in addition to differences in gradient.
This means that charge molecules have another chemical property that they need to consider and contend with. And this is the push and the pull of their electrical charge, combined with the push or pull of their concentration gradient. Remember, with electrical charges opposites attract.
And so in one scenario, we see there's a high concentration of blue circles here, outside the cell, and a low concentration of blue circles inside the cell. What's the concentration gradient? Well, the concentration gradient is from top to bottom, from high to low.
Great. Let's consider the charge now. Outside the cell is very, very positive.
Inside the cell is very, very negative. Opposites attract. So these positive balls, these positive circles, would like to get from outside the cell to inside the cell with respect to charge as well. So great, we have agreement. Here, the two gradients work in the same direction.
So these circles want to move from outside to inside, from high concentration to low, and from positive charge to negative. But... What if that's not the case?
Here the blue circles are positively charged. They're more concentrated inside the cell than outside. Their concentration gradient is pushing them from in to out.
However, outside the cell is still positively charged, while inside the cell is negatively charged here at the membrane. And so electrically, ionically, these positively charged molecules would rather stay inside the cell than out. Here the two push and pull effects, the two gradients, are opposing one another.
The concentration gradient is trying to move these blue dots from inside to out. The electrical gradient, opposites attract, is trying to keep these blue dots from outside to in. At the cell membrane, usually the inside of the cell is more negative, so this is an accurate diagram. providing a strong positive attractive force for positive ions and repelling negative ions from entering the cell.
The composite of these two forces, one being charge dependent, the other being concentration dependent, is called the electrochemical gradient and ions especially across the cell membrane are constantly contending with an electro chemical gradient, not just a concentration gradient. As we saw on the previous slide, if both forces are in the same direction, if the concentration gradient agrees with the electrical gradient, then that is a very strong force pushing a molecule from one side of the membrane to another. This is the case for sodium.
Sodium's concentration gradient behaves in the same direction as its ionic gradient. Every force is trying to push sodium into a cell. However, if these two forces oppose one another, as we also saw in the previous slide, it becomes a tug-of-war, where the concentration gradient is opposed by the electrical ionic gradient. It's possible for the two forces to be roughly equal, in which case the concentration gradient is completely opposed or neutralized by the ionic gradient. That means the overall pull on the molecule is zero.
This is the case for potassium, actually. The concentration gradient for potassium wants potassium to leave the cell. excuse me, and go outside the cell where its concentration is lower.
The electrical ionic gradient is trying to keep potassium in the cell where it's more negative and repels it from outside the cell where it's more positive. Here the ionic and concentration gradients are in almost direct opposition, and so potassium actually has a very little net force on its movement. So now with this extra complication, how do we actually move molecules against their electrochemical gradient? Despite any strong force that might be keeping a molecule on one side of the membrane or the other, sometimes for some cellular reason, the cell really needs to move that molecule against its chemical gradient, its electrochemical gradient. There are three main strategies for achieving active transport across an electrochemical gradient which opposes that movement.
First are coupled transporters. Keep in mind, all of these require energy, so we're talking about active transport, moving a molecule against a gradient that encompasses both its concentration gradient and its ionic gradient. We're moving molecules where they don't want to go.
That's active transport, it needs energy. So the first way we do this is called coupled. transporters. For coupled transporters, we actually use one molecule that's following its gradient to power the movement of another against its gradient.
What do we really mean by that? Well, this is a game I used to play when I was a kid, believe it or not. It was called Circus.
The idea here is that these colored boxes are balloons and these stick figures are clowns and you need to use the clowns to pop the balloons. I used to love this game. This was an Atari game.
I'm dating myself, but so what? The idea was that this clown that we see here in the air is falling. This clown is using the force of gravity, right?
He's dropping from a high height. He's dropping all on his own. That's energy independent.
You don't need energy to make something fall. Just lift it up and drop it. When this clown lands on this seesaw, it's going to propel this clown all the way up into the air and hopefully pop some of these balloons, because that's where you get your points. This is coupled transport. We want to get this clown up in the air, but that takes energy.
It takes energy to launch something. Just watch a shuttle liftoff and you'll see that. It takes energy to launch something up in the air against gravity. Where is the energy coming from to launch this clown into these balloons?
From this falling clown that is simply following the laws of gravity to fall. That's coupled transport. In coupled transport, you use the energy of one molecule following its gradient, just doing what it needs to do naturally.
A clown falling from a high height. A molecule falling at its concentration gradient. That's what these things do. That doesn't require energy, but you harness the energy of that movement to pump something against its concentration gradient.
You harness the energy of this clown falling to propel this clown up against gravity into these balloons. Incidentally, as bad as these graphics might be, when you missed the clown who was falling, it was pretty clear to see what happened here. even with a poor stick figure graphics of the old Atari system. I always like this image. This is a good way to show that a clown had squashed his head.
Anyway, there's two different types of coupled transport. We call them symport and antiport. The proteins that do this are called symporters and antiporters.
The sym and anti just refer to the flow of movement. For a symporter, the molecule which is following its concentration gradient moves in the same direction as the molecule being pumped against its gradient. Sym-porter, they're both going from one side of the membrane to the other in the same direction. In an antiporter, the concept is the same.
One molecule is following its gradient, powering another molecule being pumped against its gradient. But for an antiporter, the two molecules are moving in opposite directions, so we call it antiport. The second class, or second strategy for pumping things against their electrochemical gradient are ATP driven pumps. This is pretty self-explanatory, I think. These pumps use the energy of ATP, more specifically the energy derived by hydrolyzing ATP, to provide the energy for forcing the movement of molecules against their gradients.
The third strategy are light driven pumps. These are pumps that derive energy from light itself. and use that light captured energy to pump molecules against their electrochemical gradient. And we don't need to discuss this one because bacteria rhodopsin.
We went into some great detail in this mechanism in our last lecture. And so bacteria rhodopsin is the perfect example of a light-driven pump. But I don't care what you're pumping, just like the clowns, if it goes up, he's got to come down.
And if you've pumped something into the cell, sooner or later it's going to flow out. And if you've pumped something out of the cell, sooner or later it's going to flow in. You've pumped things against their concentration gradients. And their concentration gradients insist that they flow from high to low. So, for example...
If you have an ATP-driven sodium pump, which is pumping sodium out of the cell against its gradient, using energy from ATP, sooner or later that sodium is going to come back in. And most often it's going to come back in intentionally through a coupled transporter. Why is that important?
Well, sodium rushing back in following its gradient is providing some energy for coupled transport, facilitating the active transport of some oxygen. other molecule. Okay, do we get that? It's a pretty complicated system. We're putting energy in to pump sodium.
We're using ATP to pump sodium. We're pumping sodium out of the cell against its gradient. Then we turn right around and let that sodium back in through a separate channel, through a symporter or an antiporter. But the reason why we're letting it back in, because that power, that movement of sodium back into the cell carries some other molecule with it.
And it's the other molecule that we're actually moving on purpose, that we're actively transporting. I've come up with an analogy for this that I hope makes it a little bit more clear. Let's say we pump some water uphill. So pumping water uphill always requires pumping water.
Water likes to travel towards gravity. Water likes to travel downhill. So we have this stream.
I'm going to set up this massive pump. And we're going to pump water from the bottom of the hill back to the top. That takes energy. Okay, we're going to pump water to the top of this hill.
Now what's that water going to do when it gets to the top of the hill? It's going to flow right back down again. Well, you say, well, how stupid.
Look at all the energy we put in to pump the water to the top of the hill only to let it down. Why did we do that? Well, the reason we did that was because it was critically important for us to get this toy boat from the top of the hill to the bottom of the hill.
The problem was, without the water, the toy boat wouldn't flow. We needed the water to carry the boat. And so we pumped the water to the top of the hill. We expended energy in moving water so that the water would carry the boat down the hill for us. Without the water, the boat would not flow.
boat wouldn't flow. Without the water being pumped and the energy being expended for that, we couldn't get the boat to the bottom of the hill. So did we fruitlessly pump water against its gradient only to have it come down again?
It might appear so, but in reality we needed to move the water in order to carry the boat. That's what we're doing with sodium. Does it appear fruitless that we're using all this ATP to pump sodium out of the cell only to allow it back in?
Well, it may appear so, but it's actually the sodium that is carrying other molecules in or out of the cell for us, just as the water carried the boat. In fact, if the ATP-driven sodium pumps in our cells were to stop working, sodium would stop moving, of course, but it wouldn't be the only thing to stop moving. Lots of molecules would no longer be pumped in their proper direction, because those molecules follow the flow of sodium.
just as our toy boat followed the flow of the water. Many molecules rely on sodium-dependent transport, and so the ATP-driven sodium pumps are quite literally central to all of our cellular physiology. So let's start wrapping up, at least in the early stages here, by talking a little bit more about sodium, and more specifically about the sodium-potassium pump. The sodium pump, and we've referred to in the previous slide, is actually a twofer. It pumps sodium out of the cell against its gradient, but it also allows potassium into the cell.
Remember, potassium really doesn't have a gradient. Potassium's concentration gradient is in direct opposition to its ionic gradient, so the net force on potassium is near zero. But still, the sodium-potassium pump does move potassium as well. This is an ATP-dependent pump. Therefore, the pump is not just a transporter protein, it's also an enzyme.
More specifically, it's an ATPase. It's an enzyme that hydrolyzes ATP, releasing the energy and harnessing that energy of ATP. So the pump itself...
cuts ATP, releasing that energy. This pump alone, the sodium-potassium pump, is responsible for about 30%, or one-third of a cell's total ATP consumption. Can you believe that?
Think of that for a minute. Almost a third of all the energy a cell uses, it uses to pump potassium and sodium. Think of the things that the cell is doing.
Transcription. Translation, protein transport, protein regulation, gene expression regulation, everything we've talked about in this class and everything we haven't. Most of that requires energy. The cell needs to do all of it to survive.
And how does the cell spend about a third of all its total energy consumption? Pumping sodium and potassium. Unbelievable!
Pumping sodium is a very expensive endeavor, but the cell does it anyway, and why? Because it's critically important to cellular survival. By itself, this pump keeps the intracellular concentration of sodium somewhere between 10 and 30 times lower than the extracellular sodium concentration. That is simply amazing. And what it results in is a dam.
This is the Hoover Dam, one of the man-made marvels of our species. And this dam is storing an abundance of energy that we can't even comprehend. Why and how? Because all this water on this side of the dam desperately wants to flow through the dam and down the channel. That's a lot of water you see there.
That is a lot of potential stored energy. But the dam is blocking that energy, the dam is blocking that movement. This is what the cell creates with the sodium concentration.
All that sodium outside the cell, desperately trying to flow in, is like all this water stored on one side of the dam, desperately wanting to flow over it. When you allow that water to flow, you release a lot of energy. And when sodium is allowed to flow, a lot of energy is released as well. we are creating an electrochemical dam. The dam itself is the lipid bilayer.
The energy is stored in the desperate wanting of sodium to flow across it. There's a movie on Canvas that shows the function of the sodium-potassium pump in some very good detail, and I suggest you watch it just to see how this pump works in action. We'll come back to the idea of stored energy in just a second. In fact, we're going to end the lecture with it.
But before we get there, Let's talk about one other important thing that sodium and potassium do, and what the pump is related in. Water, like every other molecule, diffuses, and it goes from where it's more concentrated to where it's less concentrated. And the diffusion of water gets its own special name, osmosis.
It stands to reason, if you think about it for a second, but in any area where there are more ions, there are less water. You can't have two things in the same place at the same time. So, if there are more ions in a particular region, that means there's less water. water there. The ions are taking up the space and the water's not.
So water tends to follow ion concentrations. In other words, if there's more ions in a cell, that means there's less water in the cell. Can't have ions and water taking up the same space-time thing at the same time. And so if there's more ions in a cell, there's less water in there. But water likes to flow from high concentrations to low.
So the ions get in the cell first. That means there's less water in there. And the water wants to go from high concentrations to low concentrations, so the water rushes into the cell following the ions.
So water will move into the cell through osmosis following the ion concentration, trying to balance the osmotic gradient, trying to get the same amount of water on both sides of the membrane. For this reason, as sodium ion levels climb in a cell, water is going to follow those ions. Water's going to try to get into the cell where it's less concentrated, so water rushes in after sodium. Told you early on in the lecture that water can diffuse through the membrane itself, doesn't require channels.
There are actually channels that allow water to flow even faster. They're called aquaporins, but suffice it to say, water has no problem whatsoever getting into a cell. This is a bad proposition.
Sodium levels build up in the cell, water rushes in after it. More sodium comes in, more water, more sodium, more water. We've got this fragile, barely detectable cell membrane, barely detectable in a light microscope cell membrane.
We're setting the stage for the cell to burst. By pumping the sodium back out of the cell again, the sodium-potassium pump is actually protecting against bursting. The sodium-potassium pump is helping to keep water from rushing into the cell too much. pumping the ions that water is trying to follow back out of the cell.
Plants and protists don't do this. In fact, plants and protists don't have sodium-potassium pumps at all. Plants have cell walls.
That's what protects a plant cell from bursting. The cell wall provides a physical block. The cell can't swell beyond a certain point, and it won't burst.
Protists have contractile vacuoles. Protists will corral the water that rushes into it, and then in one shot, squirt all that water out through a contractile vacuole. And then more water will rush in, collect, and then the protist will secrete or squeeze that water back out again.
So three different strategies for keeping cells from bursting, all of them at risk of bursting because of water following ion concentrations. But animal cells pump the ions back out, water follows the ions in, water follows the ions out, perfect, no risk of bursting. Plant cells have cell walls, the cell can only swell to a certain amount of point and then it hits the cell wall, so no problem there.
And then protozoans have this neat little mechanism for squirting water out of themselves, so as the water comes in it's bucketed back out again. As far as active transport goes and coupled transport, cells of plants and cells of protists do require some type of stored energy for coupled transport, but they use protons to do that. And so there are active proton pumps in plant and protist cells that pump, that use energy from ATP to pump protons out of the cell into the extracellular environment. This is against the proton gradient.
Those protons then flow back into the cell, just like we pump water to the top of the hill, only let it flow back down. As the protons flow into these cells, they carry toy boats with them, they carry other molecules with them. This is coupled transport.
Here, this is a symporter, because the molecules are going in the same direction. And so we do get this idea of coupled transport in plant cells and protocells. It's just that they are using protons in place of water and toy boats. We use sodium.
in place of our water and toy boats, but the concepts are identical. Alright, back now and for the last time to charged ions and electrical gradients, stored energy and batteries and what it all means. Whenever we deal with charged matter, I don't care what charged matter it is, and I don't care in what context we're talking about it, we are dealing with electricity.
When charged things move, We call this current, and we measure current in units of amperes, which we abbreviate as amps. The movement of anything is kinetic energy, and that's no exception for ions. As ions move, they create current measured in amps, and this is kinetic energy.
When charged, things can't move, but they want to. We call this a potential, and we measure this in volts. All things that want to move and can't are storing potential energy. Hold the pen up in the air, and that pen wants to fall to the earth.
That is potential stored energy. But when it comes to electrical charged molecules, we call potential energy, we call it a potential, and we measure it in volts. You know this.
You encounter this every day. Take a lamp, plug that lamp into the wall. You now have 110 volts in that lamp, stored potential energy.
When the lamp is off, when the light is off, The current is zero. You have no flow of electricity through that lamp. Flip the switch, turn the lamp on.
Now electricity is flowing through the light bulb, making it glow. You now have a current in that lamp. You can measure an amperage in that lamp, because the electrons are moving through the lamp, through the light bulb, turning it on.
We are constantly dealing with these principles in our everyday life. There's no difference in these principles of the cellular membrane. At the cellular membrane, the inside of the cell is negatively charged.
We said that already, and the outside is positively charged. At the membrane, localized regions of charge imbalance. Opposites attract. The positive ions outside the cell desperately want to hook up with and interact with the negatively charged ions in the cell, and vice versa. These ions want to move.
When charged ions want to move but can't, we have a stored potential. And this is the case of the cell membrane, because with ion channels not open, these charge molecules cannot move. We call this a membrane potential because it is an electrical potential at the membrane.
And every single cell has a membrane potential. Every single cell has ions looking over the wall of the cell membrane at each other, so desperately wanting to interact. If you have an equal number of positive and negative charges across the membrane, you have a zero membrane potential.
You have no membrane potential at all, but that's not a natural state. Typically, you have more positively charged things inside the membrane, and more, I'm sorry, more positively charged things outside the membrane, and more negatively charged things inside the membrane, and so you have a membrane potential. You have a stored... Potential energy of ions wanting to move but not being able to.
The resting membrane potential, that is the membrane potential of a normal cell doing normal things, its baseline membrane potential, is somewhere in the neighborhood of 20 to 200 millivolts. Negative. 20 to 200 millivolts. Negative because we're dealing with the cell and the inside of the cell is negatively charged as opposed to the outside.
So the number reflects the unit of stored energy in volts millivolts. The charge represents the relative charge inside the cell versus outside. These forces, although they're kind of in opposition, are largely balanced.
The electric gradient that we see here, the membrane potential in other words, is opposed but balanced by the individual concentration gradients of the individual ions. We saw that for potassium. Sure, potassium would very much like to get out of the cell, but it doesn't because of its concentration gradient. Its concentration gradient keeps it, I'm sorry, because of its ionic gradient.
Its ionic gradient, being more positive outside the cell than inside, balances the force of the concentration gradient, which is trying to drive it outside the cell. That's true for every single ion except for sodium. As we saw before, sodium has a concentration gradient that is pushing it into the cell. Sodium has an ionic gradient that is pushing it into the cell.
In fact, the only thing that keeps sodium from moving is the fact that it cannot cross the lipid bilayer. It requires a channel. So when the channel for sodium is closed, sodium is kept outside the cell.
But when that channel opens, you better believe, like water through the Hoover Dam, sodium rapidly and chaotically flows through that channel, entering the cell. When sodium does so, it is following its concentration gradient as well as its ionic gradient. Any flow of ions, I don't care where they are or what they're doing, creates a measurable current in amps and changes the membrane potential because now the balance of ions on either side of the membrane has changed. Remember, we usually have a resting membrane potential of between negative 20 and 200 millivolts.
The reason for that is because we have more negative charge inside the cell than out. When sodium, a positively charged ion, goes rushing into the cell, you make that potential less. negative. You are diluting the negative charge with positively charged sodium.
That causes the membrane potential to go up closer to zero, and in fact, it could go as far as being a positive membrane potential. Since ion channels are highly selective and they only let their specific ion through, the cell accommodates this change in membrane potential by opening other ion channels, allowing the membrane potential to go up. back to what it was before, its resting membrane potential.
This implies then that different ion channels are opened and closed in a controllable and regulatable way in order to at first maintain the membrane potential and then restore it as sodium comes in and screws everything up. How is that possible? How are ion channels controlled? Well, the answer in brief is that they are gated.
Ion channels are gated. They are kept open. when they should be open and they are closed when they should be closed.
And many things can control the gate of the ion channel. Some examples are voltage-gated channels. There are ion channels that are controlled by the voltage across the membrane, the potential across the membrane. Here the channel is opened or blocked by a voltage sensor. This is a part of the protein, it's an amino acid region of the protein.
that is very sensitive to changes in the membrane potential, the voltage across the membrane. As the membrane potential changes, the voltage sensor part of the protein moves. And it either moves to get in the way of the channel, closing it, blocking it, or it moves to get out of the way of the channel, opening it.
And so here we have a very rough, brief schematic of a voltage-gated channel, closed under some voltage conditions and opened under others. In a very real and literal way, voltage-gated channels are channels gated by voltage. Voltage controls whether or not they're open or closed.
There are also ligand-gated channels. Here, some small molecule, either intracellular or extracellular, binds to the channel and forces it to open. When that molecule is present, the ion channel is open and ions flow. When that molecule is absent, the channel goes back to being closed and ions can't flow through.
So some other small molecule binds to the channel, resulting in it being opened. Some examples of small molecules which bind to these types of channels are cyclic AMP, which we've encountered before. Hormones can sometimes do this.
Lots and lots of molecules are responsible for opening ligand-gated channels. And then our final example for this are stress-gated channels. Not stress like, oh my god, I have an exam next week. That's a different type of physiology. But stress-gated channels open.
open or close, letting ions through or not, based on physical stress, pushing, squeezing, physical, mechanical movements or perturbations of the channels. That's what causes the channels to open. The neurons that are responsible for pressure sensing, touch sensing on your skin, this is how they work.
As you press down on something, that physical stress, the squeezing of that region causes channels, ion channels to open. And that stimulates neurons in your skin to say, hey, we're feeling pressure here. Completely different sensation than pain, which is why when the dentist gives you Novocaine, you don't feel pain, but you feel a hell of a lot of pressure. Because the way we feel pressure and the way we feel pain are two completely different mechanisms.
And our pressure sensation, the fact that we've come in contact with something, is due to mechanically opening ion channels and neurons at the skin. So let's wrap up then with our discussion of ion channels. All ion channels. regardless of how they're gated, are constantly in a state of flux between opening and closing. Even when we say that a gated channel is closed, it's not a hundred percent.
Closed channels do spontaneously open occasionally, letting ions through. This means that membrane potentials are not quite steady. Instead, membrane potentials are constantly fluctuating around a baseline value. What we mean by this is that when channels are opened by their stimulus, it's simply that they just spend more time open than before.
Closed channels are very, very often closed and open very briefly. Open channels are very, very often open and closed very briefly. That's the only difference. But still, it's constantly this state of flux.
And so what we mean by this is, if you just bear with me for a second here, If we were to sketch this out, here's a graph and we think of the membrane potential as a nice steady line, right? The resting membrane potential right around negative 20 millivolts, a nice steady line. But it's not true. With all these channels opening and closing, the membrane potential goes up a little bit and then the cell compensates and brings it down.
And then it goes up a little bit, the cell compensates and brings it down. So this is what we mean. Membrane potentials aren't really quite steady, they fluctuate. little bit up, always constantly trying to meet that steady state, always missing it and overcompensating.
So we're always fluctuating around a baseline value, and this is because channels are spontaneously opening, and then they close, you open other ones to compensate, closing the first and constantly dancing around this. So that's all we mean there. So all that changes by voltage gating or ligand gating or stress gating, all that changes is the frequency or probability of opening. We're shifting these channels to being open more and closed less rather than closed more and open less.
Once a channel is open, whatever channel it is, ions will flow through those channels more and more. Membrane potential changes as a result. This serves as an electrical trigger or an electrical stimulus or an electrical signal for many, many, many other cellular activities.
Thank you. and you get yourself a cascade. You get yourself a cellular response to that electrical signal.
I'm not going to go through these. This is table 12.3 from your textbook. There's some examples of the ion channels that we have in our membrane, where they're typically found, and the function that that ion channel is responsible for.
And you can see that many of these are neuronally biased. Many of these are neuron functions. But we have these ion channels to elicit cellular responses. That's all we're trying to get across here.
And again, the changes in membrane potentials, the changes in ion flow, sets off these cascading effects like dominoes. First one thing happens, then another thing happens, then another thing happens in the cell, until the cell's entire behavior has changed as a result of this electrical stimuli. In addition, while all that's happening, other channels are opening and closing, pumps are being activated, and the cell is constantly trying to restore its membrane potential back to its resting state.
And eventually we'll achieve that, and once the cell has restored the membrane potential, the cellular response ends, and the cell goes back to its resting state until it gets another stimulus. So this beautiful system of transport across the membrane, really having far-reaching effects on the physiology of the cell. So what did we talk about today? Well, we started off just introducing the idea of transport proteins.
And transport proteins are nothing more than specialized custom proteins that serve as doorways through the cell membrane, allowing molecules to move. We introduced the idea of the ions right away in the lecture, talking about sodium being the most plentiful ion found outside the cell relative to the interior, and potassium has the opposite distribution, where it's more plentiful inside the cell than out, and I gave you guys the mnemonic of kin to remember that. Channels are usually electrically neutral, they just sit there, they truly are open doors or open trap doors, where when opened, the right molecules can move through them. Whereas transporters have moving parts, and so they usually require energy in some form.
There are two forces that work together, affecting a molecule's movement across the membrane, or at least its desire to move. One is the concentration gradient, where molecules like to move from high concentration to low. The other is the charge-dependent gradient, where molecules want to move from their own charge towards opposite charge.
These two forces working together is referred to as the electrochemical gradient, and this is the gradient that is responsible for the movement, or desired movement, of ions across a membrane. There are three main strategies that are used by cells to pump ions against their electrochemical gradient. Coupled transport, that idea of water being pumped uphill to bring the boat down.
You pump one ion against its gradient to let it carry another ion through. ATP driven active transport where the energy comes from ATP or like bacteria redox in the light driven pumps we've discussed in the last lecture. We focused fairly extensively on the sodium potassium pump.
We said that the sodium potassium pump that exists in our cells not only exists to pump sodium out of the cell but which is against its gradient but it also allows potassium into the cell keeping a balance of these ions. By pumping sodium out of the cell, the sodium potassium pump keeps our cells from bursting, keeps water from overwhelming the interior of our cell, which is a good thing. And then we ended with this discussion of the far-reaching effects of changes in membrane potential. Once channels are open, regardless of what channel they are, regardless of how they were gated, and what stimulated their opening, ions will flow.
That's going to change the membrane potential, which causes two broad responses in the cell. Whatever cellular response and change in physiology was desired by the change in membrane potential, the cell is responding to some type of electrical stimulus as well as the response which is constantly trying to counteract that and restore the membrane potential back to rest. So it's a very very complicated system which we leave intentionally vague simply because the scope of this course we don't really need to have the comprehensive understanding of these electrical changes. You like this?
If this is interesting to you, then neuroscience is your thing. Alright, so we're going to step away from the membrane in our next lecture. We're going to move right along onto chapter 15. Chapter 15 is going to be broken up between two lectures.
First half of chapter 15 is going to deal with the organelles in some great detail. The second half of chapter 15 goes back to the idea of transport, but now intracellular transport as opposed to transport across membranes. And we'll leave it for the next two lectures, but we're moving on to chapter 15. after this.