Oxford Biochemistry Interview: The Potassium Ion Channel Question

Harry · Biochemistry (Oxford)

Hi guys, my name is Harry, and I studied Biochemistry at Oxford University, class of 2010. I want to share the kind of interview question that biochemistry applicants can expect, by working through one of the questions I thought was among the most difficult.

The question

The question is about the selectivity filter of the potassium ion channel. Inside the filter, carbonyl oxygens point towards the incoming potassium ion, and the filter is just wide enough to fit a single potassium ion. To picture it, imagine those carbonyl oxygens lining a narrow opening, angled towards the ion passing through.

The real question is this: why can't sodium ions pass through the channel, given that they carry the same effective charge of plus one as potassium ions, and are actually smaller?

How to approach it

Your interviewers would not expect you to know the answer straight away, so the best thing to do is start by stating the obvious and building from there.

First, there is an electrostatic attraction between the positively charged potassium ions and the negatively charged carbonyl oxygens. Second, potassium ions are larger than sodium ions.

The key idea to reach is about hydration. In solution, an ion is surrounded by a shell of water molecules. When a potassium ion enters the channel, it loses that hydration shell, and in exchange it forms new interactions with the carbonyl oxygens lining the filter. Crucially, the energy gained from this new attraction is large enough to compensate for the energy lost when the hydration shell is stripped away. The filter is effectively sized so that the carbonyl oxygens sit at just the right distance to substitute for the water the potassium ion has given up.

Now the answer. Because a sodium ion is smaller than a potassium ion, its reduced proximity to the carbonyl oxygens means the resulting electrostatic interaction is weaker than it is for potassium. That weaker interaction is insufficient to compensate for the energy cost of a sodium ion losing its own hydration shell. So the sodium ion effectively stays hydrated and does not pass through, even though it is smaller.

The mindset that matters

The point of a question like this is not recall, since interviewers do not expect you to have learned the answer in advance. What they want to see is whether you can reason from first principles, in this case electrostatics, energetics, and the idea of dehydration, and whether you can talk them through each step of your thinking. Start with the obvious, build carefully towards the less obvious, and keep vocalising your reasoning so your interviewer can follow you.

There we go, our answer to the ion channel question. I hope you found it intellectually stimulating. If you would like to learn more about preparing for an Oxford or Cambridge biochemistry interview, do get in touch with us.