Now, when you dissolve potassium chloride crystals in water, the same thing happens. The potassium and chloride would dissolve. Chloride is happy in water, and the positive potassium, much like sodium, is dissolved in water, with the oxygens pointed to the potassium. What this means is that these positive ions are happy in water.
To go into a channel, they have to come out of the water, and come into a little part that we call the selectivity filter. The potassium channel is such that it has oxygens, the same kind of atom as in the water, but they are part of the protein itself. And these oxygens are held, so that when the potassium comes in, instead of being close to the oxygens of water, it's close to the oxygens of the protein. Now, sodium can do that, too. But what the potassium channel does, it makes a hole that's a little bit bigger. It's a good size for potassium, and it's a little too big for sodium.
When we consider selectivity, let's think about sodium. Sodium can be in water, or it could be in the potassium channel. And where it's going to be depends on where it's energetically most stable. Now, in water, the oxygens from the water get very close to the sodium ion, but in the potassium channel, because the little hole that the channel provides is a little too large for sodium, the sodium would rather be in the water. And so what happens is it partitions or it stays in the water. The potassium, on the other hand, seems to be equally happy in the potassium channel and in the water, because the hole made by the channel is just the right size for potassium. And you have to understand, it's an energetic balance between "does the ion want to be out in the water?" or "does it want to be in the channel?" And to the best we can understand, this structure, of course, allows us to make this as a hypothesis. What it appears to us is that the sodium ion would rather be in the water than in the channel due to the hole size, whereas the potassium ion is equally happy in the channel and in the water, and thus you have a potassium channel.
SA: When you determined the structure of the potassium channel two years ago, was there anything completely unpredicted by previous mutagenesis studies or other studies?
Yes, there were many features that were really not predicted. People certainly had an idea that there would be a protein with a hole down in the middle, and in fact the idea that there would be probably oxygen atoms available to surround a potassium ion in the selectivity filter. And we even knew which amino acids would make the selectivity filter; we knew that from our own mutagenesis work in this lab. So we knew which amino acids would do it, but we did not know what kind of structure they would take. In order to understand that, we really had to see it, because there are so many ways you could arrange a given set of amino acids.
Then there was a feature of the channel that was altogether unpredicted. We never would have been able to predict it without seeing it. And that was this very strange arrangement of the helical segments of the channel. Proteins are made of some basic structural elements, alpha-helices and beta-sheets, and these elements were described a long, long time ago. It turns out the potassium channel is mostly alpha-helices, and it has a certain set of alpha-helices that are arranged in a very interesting way. The alpha-helix has polarity in that it has two ends; it is not the same going forward and backward. One of the differences in the ends is the amount of charge. One end that we call the amino terminus, the N-terminus of the helix, tends to be plus-charged--here again we are talking about charges--and the C-terminal end of the helix tends to be negatively charged. The channel's architecture is such that it points four helices, the negative ends of the helices, straight at the middle of the membrane.