P2X receptors: dawn of the post-structure era

P2X receptors are non-selective cation channels gated by extracellular ATP. They play key roles in various physiological processes such as nerve transmission, pain sensation and the response to inflammation, making them attractive drug targets for the treatment of inflammatory pain. The recent report of the three-dimensional (3D) crystal structure of zebrafish P2X4.1 represents a step change in our understanding of these membrane ion channels, where previously only low-resolution structural data and inferences from indirect structure–function studies were available. The purpose of this review is to place previous work within the context of the new 3D structure, and to summarize the key questions and challenges which await P2X researchers as we move into the post-structure era.