The ClC-0 chloride channel is a ‘broken’ Cl−/H+ antiporter. Nature Structural & Molecular Biology 15:805–810. doi

Ion channels have historically been viewed as distinct from secondary active transporters. However, the recent discovery that the CLC ‘chloride channel ’ family is made up of both channels and active transporters has led to the hypothesis that the ion-transport mechanisms of these two types of membrane proteins may be similar. Here we use single-channel analysis to demonstrate that ClC-0 channel gating (opening and closing) involves the transmembrane movement of protons. This result indicates that ClC-0 is a ‘broken ’ Cl−/H+ antiporter in which one of the conformational states has become leaky for chloride ions. This finding clarifies the evolutionary relationship between the channels and transporters and conveys that similar mechanisms and analogous protein movements are used by both. Members of the CLC chloride-transport protein family facilitate an impressive array of physiological functions including endocytosis, skeletal muscle excitability, neuronal chloride distribution and epithelial ion transport1–3. This diversity of physiological function is accompanied by a surprising diversity in thermodynamic mechanism. Roughly half of the CLC family members are chloride-selective ion channels, which provide passive pores tha