ATP Binding and Channel Activation in P2X Receptors

Abstract

Purinergic P2X receptors are a family of nonselective cation channels gated by extracellular adenosine 5?-triphosphate. They are important drug targets primarily because of their involvement in neuropathic pain and inflammation. ATP binds allows Na⁺ and Ca²⁺ to pass through the channel pore, thus causing membrane depolarization and a?ecting various downstream Ca²⁺-dependent signaling processes. A concerted effort by investigators over the last two decades has culminated in significant advances in our understanding of where ATP binds and how ATP binding leads to channel opening and ion flux. The recent publication of the crystal structures for both the closed and open channel conformations of the zebrafish P2X4 receptor sheds new light on how P2X receptors work. In this review, we will attempt to present the existing functional data regarding ATP binding with the available crystal structure data and different experimental approaches that have been used to explore the ATP-binding sites.