Bacterial and plant antiporters.

Articles in this chapter emphasize the phenomenon of ion exchange across biomembranes. This topic has been of interest at least since 1947, when Hans Ussing articulated his model of ‘exchange diffusion’ to account for an unexpected elevation in the rate of 22Na+ efflux from skeletal muscle (Ussing, 1947). Ussing had tried to measure net Na+ movement by following tracer flux, but found that this approach greatly overestimated the true value. To explain this overestimate, Ussing postulated that isotopic flux reflected only isotopic exchange rather than net movement of mass, and he proposed the following model. Perhaps a negatively charged carboxyl group on some membrane element accepts the positively charged 22Na+ so that the neutral complex can move through the membrane (mechanism unspecified) without interference from the electric field? If so, at the opposite surface, tracer could be discharged, replaced by (nonradioactive) 23Na+, and the neutral complex would return to the original membrane surface, and at that point 23Na+ would be released to let the cycle begin again. Clearly, by following the movement of 22Na+, one might considerably overestimate the true net movement of Na+ itself. Note that Ussing’s conceptual analysis of exchange is the same as that offered by Widdas (1952) in the latter’s presentation of the more general idea of a membrane carrier. Moreover, the idea that ion pairs might constitute essential elements in the movement of charged compounds is as useful today as it was in 1947. Indeed, we need only modify Ussing’s proposal in minor ways to arrive at a view of ion exchange pertinent to the topics treated here. First, we would specify that the catalyst for transport is a specific kind of membrane protein – for example, one having 10–12 transmembrane helices, this being the most prevalent structural element found among the various porters now known. Second, we would note that the physiologically relevant mode of exchange must be a heterologous, not a homologous, event – that is, that Na+ might exchange with H+ (as discussed in this chapter) or Ca2+ or K+ or some other cation; or that one anion might exchange with another anion – inorganic phosphate (Pi) with glucose 6-phosphate (discussed here), ADP with ATP, or perhaps Cl2 with HCO3. I note that, although not unimaginable, there is no good example of an exchange reaction in which the carrier mixes passengers of opposite charge; this deficiency points to an instructive role for the pairing of charge(s) between porter and passenger, as first suggested by Ussing. Subsequent to Ussing’s work, cation exchange systems continued to be of theoretical interest. In particular, they played an important role in the chemiosmotic hypothesis of Peter Mitchell (Mitchell, 1961). In that case, such ‘antiporters’ (as we now call them) were considered to be essential if mitochondria were to express a membrane potential,