Figure 4. Examples and models of slow conformational changes in P2X receptors displaying pore dilation.

A. Current-voltage plots for example recordings of the I₁ and I₂ states for P2X2 receptors expressed in Xenopus oocytes are shown. The I₁ state has low permeability to the organic cation NMDG⁺ (hence a negative reversal potential). With time the permeability to NMDG⁺ increases, indicated as a shift in reversal potential by ~ +16 mV. B. Representative images of a Xenopus oocyte bathed in YOPRO-1 before and during 100 µM ATP (for 30s). The oocyte becomes fluorescent as YOPRO-1 enters the cell, presumably via the I₂ state. The data shown in A and B are from Supplementary information accompanying (Chaumont and Khakh, 2008). C. Diagrams illustrating the differences between the Panx-1 and gating models for the I₂ state. In the gating model, small cations, organic cations and dyes enter due to slow conformational changes in the P2X pore. In the Panx-1 model, organic cations and dyes enter via an accessory ion channel protein called Panx-1. On balance the field is converging on the gating model, but there is also evidence for the Panx-1 model in the case of P2X7 receptors that are natively expressed (as discussed in the main text). In both models, the cytosolic domains of P2X receptors are important.