Most physiologists would not have too much difficulty describing the difference between a channel and a transporter. A channel is a hydrophilic pore through a membrane, which can let through many thousands of ions each time it opens. It can be selective for particular ions, but ions can only move `downhill' – that is, they cannot move up their electrochemical gradient. By contrast, transporters move far fewer ions, but some have the potential to move them up their electrochemical gradient – what is called `active transport'. This distinction is fundamental to physiology. It is thus surprising to find that the archetype of a major class of ion channels, the chloride channels, or ClCs, actually moves chloride up its electrochemical gradient in exchange for hydrogen ions: that is, it behaves as an exchanger.

Alessio Accardi and Christopher Miller work on a chloride channel from Escherichia coli, the bacterium that we carry around (in kilogram quantities) in our own guts. ClC-ec1 is an archetypal chloride channel, and its sequence is close enough to the chloride channels of animals to be a clear member of the family. Like other chloride channels, it lets through chloride ions and is activated, not by membrane voltage, but by low pH. It has thus been seen as a proton-activated chloride `leak' channel that may help E. coli live in the acid environment of our guts. However, the simple story does not stand up to detailed investigation. When studied in isolation, the reversal potential of the channel (the potential at which no current flows through the channel when it's open) is 30 mV, rather than the 45 mV that would be predicted for a pure chloride channel from the transmembrane chloride distribution. This must mean that the channel is permeable to more than just chloride. In addition, the channel has relatively low conductance, letting through only 10<sup>4</sup>–10<sup>5</sup> ions per second, compared with 10<sup>6</sup> ions per second through the classical sodium channel. In their paper, Accardi and Miller reach the stunning conclusion that ClC-ec1 is actually not a channel at all, but an exchanger that moves two chloride ions in one direction for one proton in the other. Thus, the activation by low pH is not a gating effect but simply reflects increased activity of the exchanger when extra protons are available. The low conductance is thus a property of the `channel' not being a channel at all, but an exchanger. And critically, by imposing an appropriate proton gradient, it is possible to drive a chloride flux against its electrochemical gradient – a clear example of `secondary active transport'.

The authors go further. By studying the recently elucidated crystal structure of their channel, they identified a glutamate residue that they predicted might be critical for Cl^–/H⁺ coupling. When this amino acid was changed to alanine, ClC-ec1 became a `classical' chloride channel with no sensitivity to pH.

The authors wryly remark that the distinction between a channel and a pump may be exceedingly fine. Given that many chloride channels are found near big pH differences – they've been argued to be the classic `partner' for the proton-pumping V-ATPase – it may thus be pertinent to re-examine our understanding of these `channels' in animals, too.