h2g2 The Hitchhiker's Guide to the Galaxy: Earth Edition

I did a little Google research on this subject and here is probably more than you cared to know:

1) There are many, many different types of ion channels. Some are opened or closed by a messenger molecule binding to them (like a neurotransmitter), some by chemical modification of one or more of their amino acids (for example by adding or removing a phosphate group), some by chemical modification of the lipids in the cell membrane surrounding them, and some by sensing the voltage potential in the surrounding environment. The last group, voltage-gated ion channels, are the subject of the original question.

2) Voltage-gated ion channels appear in many cell types, not just neurons. They are essential to the function of muscle cells and probably every other cell in our bodies. They seem to occur in prokaryotes too.

3) Voltage-gated ion channels, in mammalian cells at least, are usually made up of multiple peptide units, often encoded by different genes. The different sub-units of the channel change shape in response to the voltage potential between the inside and outside of the cell. The shape change either opens or closes the roughly cylindrical pore through the lipid bilayer membrane, either by changing the pore itself or moving an external protein sub-unit to block or unblock one end of the pore.

4) The parts (domains) of the proteins that form the ion channel itself through the cell membrane are mostly in alpha-helix shape(rather rigid cylindrical spirals, sort of like DNA strands except only a single strand). They have mostly hydrophobic amino acids on their lipid-membrane-facing sides but a variety of amino acids on the channel-facing side. The size and charges of the channel-facing amino acids have some role in determining which kind of ions can go through the channel when open or closed, i.e. whether it is a sodium, potassium, calcium, chloride or H+ channel.

5) The protein domains that are on the outside or inside of the cell-membrane and the ion pore itself can arrange themselves in a greater variety of shapes. They usually have more hydrophilic and charged amino acids since they are in contact with watery electrolyte rather than the lipid membrane. Some or maybe even most of these external domains are the voltage sensing part that controls the channel. The voltage-sensing domains typically have many amino acids with charged side chains that can change shape in response to the concentration of charged ions in the surrounding electrolyte.

6) It seems there is still lots of investigation and debate on the exact mechanisms whereby the voltage-sensing domains interact with the trans-membrane domains to open or close the channel. However, one general principle is clear. The exact amino acid sequence in certain parts of the proteins can dramatically change the functioning of the channel, for example determining at which potential voltages the channel opens or closes. Mutations of certain single amino acids can change the opening or closing voltage, the ion selectivity or even shut down the channel entirely.

7) Research on the exact structures and mechanisms of various ion channels is big business because ion channels are the key to many diseases and physiological processes. Googling "'voltage gated potassium channel' neuron structure" gets 70,400 hits. There is a bewildering array of variants of each ion channel sub-unit that can be mixed and matched to give ion channels with different characteristics. It looks like a job as a researcher on ion channels has very good long-term security outlook since it will take an eternity to sort through it all.

Here is an abstract for one of the more comprehensible of recent papers: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WSS-4MD97CB-B&_user=10&_coverDate=11%2F22%2F2006&_fmt=summary&_orig=browse&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=440ea7ffbfcb153f2fbb4d5a2ede34f8

Here's a professor's home page with good explanation and pictures: http://www.pitt.edu/~biohome/Dept/Frame/Faculty/grabe.htm

Here's another paper abstract I wanted to include just because the authors are at the *Institute of Hyperexcitability*: http://stke.sciencemag.org/cgi/content/abstract/sigtrans;2005/307/pe50
Wouldn't you like to work at a place with a name like that?

that'd make a good guide entry....