Section on Cellular Signaling, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4510, USA
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. P2XRs are homomeric or heteromeric
proteins, formed by assembly of at least three of seven subunits
named P2X
1-P2X
7. All subunits possess intracellular N- and 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 Ca
2+ 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
P2XRs 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 P2XRs, including
heteromerization, chimerization, mutagenesis, and biochemical
studies.
