Fluxion

As I seem to remember describing on one or more previous occasions that I can't be bothered to track down now, cells are more-or-less discrete units, essentially little bags of biochemical glop. The interior has a pretty complicated structure that we don't need to be overly concerned with right now, but what we do need to be concerned with is that their chemical composition usually differs from what's outside in rather important ways. Indeed, managing those differences is one of the main consumers of energy in pretty much any living organism. For a cell -- or anything made up of cells -- being alive basically equates to being able to control your chemical content. If you don't have that ability, you are dead.

The membrane that divides out from in for a cell is somewhat watertight, but not hermetically sealed: if it were fully so, the cell would be in big trouble. Cells don't and can't exist in a vacuum. They must interact with their surroundings to live. For big multicellular organisms like you and me there's a stupendous amount of intercellular communication required for even the most minimal bodily function. And even single-celled lifeforms like bacteria need to be able to sense their environment in order to navigate -- and devour -- it.

For good logistic reasons, then, the membrane is riven with little switchable channels that can allow various kinds of traffic in and out with a high degree of selectivity. (There are other mechanisms as well, but let's fry one kettle of worms at a time.) A good many of the things that get shipped over the great divide are ions, so as well as changing chemical composition their movements also change the distribution of charge -- that is, they are electrical currents. As such, they are measurable.

The field of electrophysiology is concerned with exactly that: measuring bioelectrical currents and determining what they mean. Sounds pretty simple, right?

The problem is that there are really quite a lot of distinct currents involved, operating over a wide range of different timescales, initiated, modulated and shut off by a wide range of factors -- including other currents. Much of that complexity is not directly measurable. Most of the time what is measurable is just the aggregate of it all.

The measurement of ion currents is commonly performed by patch clamp techniques, to which we have fleetingly alluded before in ways that aren't worth linking to here. The fundamental instrument of the patch clamp is a fine glass pipette used as an electrode -- not coincidentally, also the basis of SICM -- which is placed against the membrane surface of a cell, creating an isolated -- and controllable -- route for ion conductance. There are, off the top of my head, five common patch clamp configurations, but we can group them as two: whole cell, in which the overall net current flow across the entire cell membrane is the target; and single channel in which the quantile flows associated with a small number (the name misrepresents somewhat) of individual ion channels are measured. (It should go without saying that whole cell currents are basically an aggregation of single channel currents, but at a scale where the individual openings and closings are usually undetectable.) A patch clamp measurement normally -- although not always -- records the currents' time course, which is to say, what are the electrical variations associated with the ion channels' opening and closing over some number of seconds or minutes.

Because there are so many different kinds of ion channel, controlling passage of several different ion species in response to a large number of environmental triggers, it is typically very difficult to pick apart the contributions of each kind to the overall current, but each has its own particular row to furrow and will often respond differentially to various chemical agents, such as toxins or drugs. This is where the pharmacology comes in. Experimentally, it is often possible to differentiate between channels by chemically enabling or inhibiting them, which in turn can allow one to start to analyse what is going on in terms of transmembrane communications in different cells. And the time courses of different channels in a given context will themselves differ, which can sometimes be identified as pieces of the aggregate time course.

It may not be obvious from the above why anyone could or should possibly care about any of this, but consider: all of these channels serve a physiological function, and that function is usually highly relevant to the function of their host cell within the body as a whole. Communication is one of the key functions, and that is the basis of pretty everything that makes us what we are: sensations of pleasure and pain, thoughts and moods, excitation and depression. These infinitesimal ion chemical flows are at the root of how we work.

Even if, at first sight, they're nothing but impenetrable fluxions.
Posted by matt at December 6, 2007 11:04 PM