A second substrate can inhibit transport of the first by binding to the carriers thus reducing the number of carriers free to complex with the first. However, it is also possible for a second substrate to increase transfer of the first. In the extreme case if the carrier can only change conformation while a substrate is bound, the carrier is an obligatory exchanger and net transfer of one solute can only occur in the presence of another. More generally efflux of a substrate can, by increasing the rate of changes from inward to outward facing conformations increase the availability of carrier to collect a different substrate on the outside and hence its influx. Exchange whether or not obligatory can result in secondary active transport in which uphill transport of one solute is driven by downhill flux of another [322–324, 326]. Manifestations of this coupling are sometimes called variously counter-transport, counter-flow or trans-stimulation (see Fig. 12).