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Image: The Rockefeller University POTASSIUM ION CHANNEL, whose architecture was revealed by MacKinnon's lab, is embedded in the cell membrane. It is designed such that potassium ions, but not the smaller sodium ions, can pass through it.

I guess to answer the question, the very initial excitement about it was to understand electricity in living cells. And then the questions became more focused as people understood that there are channels through the membrane. They, and myself, wanted to know "How do they work?"

Different kinds of channels only let a specific ion through. So a sodium channel is called a sodium channel because when it is open, only sodium goes through and potassium doesn't go through. Sodium is a little spherical atom with a +1 charge on it, and the sphere of sodium is a little bit smaller than the sphere of potassium. They both have the same +1 charge on them. The sodium is 0.95 angstrom in its radius, and the potassium is 1.3 angstroms in its radius. So they are just a little bit different, and yet the sodium channel only lets sodium through, and the potassium channel only lets potassium through. So the question that I really wanted to understand is, what is the chemistry for this, what we call "selectivity." How does the channel tell the difference between a potassium and a sodium? That's another exciting, fascinating feature for me that's driven my research.

SA: As far as I know, you found out what makes the potassium channel selective for potassium ions, as opposed to sodium ions. But why doesn't it let sodium ions through if they are smaller?

RM: When you consider what factors go into which ions go through the channel, there are really two sides of an equation you have to consider. The ions, like potassium and sodium, are very happy in water. So, for example, when you add sodium chloride (table salt) crystals to water, they dissolve very well in it. What's happening there is that the +1 sodium ion is separating from the -1 chloride ion, and they float off independently, or fairly so, in the water. What that means is ions, like sodium and chloride, are happy dissolved in water. And the reason they are happy dissolved in water is, in the case of sodium, that the water structure is such that it can organize around the sodium ion and stabilize it.

The sodium has a +1. And the water doesn't have a charge, but actually has a "partial charge separation." The H2O is like a little Y, where the oxygen is at the meeting point or the stem of the Y, and that's a little bit negatively charged. An equal amount of positive charge would be balanced over the hydrogens, the forks of the Y. So although it doesn't have a net charge, it has what we call a "little charge separation." The waters actually gather around, pointing the partially negative oxygen against the positive sodium ion, and we say the sodium is "hydrated" by water. If we could imagine seeing a sodium ion in water, what you would see is, the sodium would be in there, but then waters would be gathered around it, oriented with their oxygens toward the surface of sodium, so the partial negatives of the waters would be close to the positive charge of the sodium, since opposite charges attract, and that would be a stable situation.

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