Ligand Gated Ion Channels

Voiceover: Have you ever wondered how our nervous system like our neurons and our brain, can react so quickly? Well, the reason is because of ligand-gated ion channels. Ligand-gated ion channels are one type of major membrane receptors. The three categories are: ligand-gated ion channels, G protein-coupled receptors, and lastly enzyme-linked receptors. Today we're going to focus on the ligand-gated ion channels. These are also called ion channel linked receptors. Ligand-gated ion channels are transmembrane ion channels that open or close in response to the binding of a chemical messenger like a ligand. Like we mentioned, a very common place to find ligand-gated ion channels are in electrically excitable cells like neurons. The reason why is because these ion channels react really quickly to the binding of ligands, and so they're very commonly found in cells that need to react very quickly to stimulus. When we talk about transmembrane ion channels, what we really mean is they are transmembrane or integral proteins that also have a channel, a hole through them, in which things can move in and out. To start out with, let's say we have an ion channel that looks something like this. Let's go ahead and color that in. This particular channel at the moment is closed. Right now, we have our intracellular environment, this is where our cytosol and all of that stuff is. This is our extracellular environment. As you can see, this ion channel has a weird kink in it, and this is a place where a messenger, like a ligand or a neurotransmitter can bind. Let's say we have a ligand that looks like this. This is our ligand. This ligand can bind in there. Notice that the shape of our ligand is complementary to the shape of our channel, so it fits right in there. Only specific ligands can bind to specific channels. This is what we call our "lock and key", or a more updated one is called "induced fit". Once this ligand binds, what it'll actually do is it'll cause this closed channel to actually open up. We'll actually see this channel open up, kind of like that. Now this is our open channel. One really interesting thing about ligand-gated ion channels, is if you look at where this ligand binds, the binding site of this ligand is not anywhere near the actual channel. The reason why is because this is what we call allosteric binding. The ligand binds to what we call an allosteric site. This is a place that's away from the ion channel. But what happens is, once the ligand binds, it can control the opening and closing of the ion channel by altering the protein conformation of the entire protein. Once it binds, a channel opens in a different place, and the ion permeability of the entire plasma membrane can quickly change. Remember this is not just one thing happening. When these ligands are binding, there are many of these channels scattered throughout these cell membranes, so all of these are opening and closing all at once. Once this channel opens it'll let ions, like potassium, sodium, chlorine or calcium being the most common, move through the open channel. Once these ions are moving in and out, this will cause a change in the electrical properties of a cell. In other words, you'll convert this extracellular ligand signal, into an intracellular electrical signal. Once these ions move in, or they can also move out, you'll have an intracellular electrical response, electrical signal happen inside the cell. There are two things I'd like to note real quick. The first is that the allosteric binding site of a ligand, this area that is complementary to the ligand, can be intracellular, it can be inside the cell, but that's considered pretty rare. Why might that be? Well, we'd have to think about the main purpose of membrane receptors. We have to realize that they generally are meant to respond to extracellular signals, to things that are on the outside of the cell. Generally speaking, ligand-gated ion channels will have the binding site on the extracellular side. The second thing to note is that it is possible for there to be multiple allosteric binding sites for ligands. It's possible that there are multiple of these kinks, of these complementary shapes, that let the ligands bind for each protein. Finally, I'd like to clear up two quick misconceptions. Ligand-gated ion channels are easily confused with two types of ion channels. They are not the same as voltage-gated ion channels. Voltage-gated ion channels rely on the difference in membrane potential. As we recall, ligand-gated ion channels actually respond to the binding of a ligand. The voltage-gated ones only depend on the difference in membrane potential. The second one they're easily confused with is what we call stretch-activated ion channels. As the name implies, stretch-activated ion channels depend on what we call the deformation of the cell membrane, or the cell membrane stretching and being pushed and being stressed. In summary, ligand-gated ion channels are one type of membrane receptors. They are transmembrane ion channels that open or close in response to the binding of a chemical signal like a ligand. You'll notice that here our channel is closed, and once this ligand binds to an allosteric site, which is a site that's not on the channel itself, it'll let ions such as potassium and sodium and so on move through the membrane. This will actually cause an intracellular electrical signal. We have one outside ligand, and this will allow us to have an intracellular electrical signal. This will actually tell the cell to do something. Ligand-gated ion channels are not to be confused with voltage-gated channels, which only rely on a difference in membrane potential, and they are not to be confused with stretch-activated ion channels, which are affected by a deformation of the cell membrane.