Rectification of ATP-gated current of rat P2X2 and P2X7 receptors depends on the cytoplasmic N-terminus

The phenotypes of ATP-gated currents thought ionotropic P2X channels depend on the composition of the oligomeric receptor. We constructed chimeric P2X2/P2X7 receptors to study the effect of cytoplasmic domains on rectification of current flow through the open channel. We found that the identity of the N-terminus determines the pattern of rectification, with chimeric receptors containing the N-terminus of the P2X2 receptor displaying inward rectification, and chimeric receptors containing the N-terminus of the P2X7 receptor displaying slightly outward rectification. In contrast, rectification of current through chimeric receptors with swapped C-termini always mimicked the wild-type receptor. Thus, our findings suggest that the N-terminus of P2X receptors regulate ion flow through the channel pore and are responsible in part for determining current rectification.