Transporters as Channels

This review investigates some key aspects of transport mechanisms and recent advances in our understanding of this ubiquitous cellular process. The prevailing model of cotransport is the alternating access model, which suggests that large conformational changes in the transporter protein accompany cotransport. This model rests on decades of research and has received substantial support because many transporter characteristics are explained using its premises. New experiments, however, have revealed the existence of channels in transporters, an idea that is in conflict with traditional models. The alternating access model is the subject of previous detailed reviews. Here we concentrate on the relatively recent data that document primarily the channel properties of transporters. In some cases, namely, the observation of single-transporter currents, the evidence is direct. In other cases the evidence—for example, from fluctuation analysis or transporter currents too large to be described as anything other than channel-like—is indirect. Although the existence of channels in transporters is not in doubt, we are far from understanding the significance of this property. In the online Supplemental Material, we review some pertinent aspects of ion channel theory and cotransport physiology to provide background for the channels and transporters presented here. We discuss the existence of channels in transporters, and we speculate on the biological significance of this newly unveiled property of transport proteins.