Molecular dissection of purinergic P2X receptor channels

The P2X receptors (P2XRs) are a family of ATP-gated channels expressed in the plasma membrane of numerous excitable and nonexcitable cells and play important roles in control of cellular functions, such as neurotransmission, hormone secretion, transcriptional regulation, and protein synthesis. MRS are homomeric or heteromeric proteins, formed by assembly of at least three of seven subunits named P2X(1)-P2X(7). All subunits possess intracellular Nand C-termini, two transmembrane domains, and a relatively large extracellular ligand-binding loop. ATP binds to still an unidentified extracellular domain, leading to a sequence of conformational transitions between closed, open, and desensitized states. Removal of, extracellular ATP leads to deactivation and resensitization of receptors. Activated P2XRs generate inward currents caused by Na+ and Ca2+ influx through the pore of channels, and thus mediate membrane depolarization and facilitation of voltage-gated calcium entry in excitable cells. No crystal structures are available for MRS and these receptors have no obvious similarity to other ion channels or ATP binding proteins, which limits the progress in understanding the relationship between molecular structure and conformational transitions of receptor in the presence of agonist and after its washout. We summarize here the alternative approaches in studies on molecular properties of MRS, including heteromerization, chimerization, mutagenesis, and biochemical studies.