Simulations of pore dilation using the kinetic model. Pore dilation is manifest as a reversal potential shift (compare Fig. 3). The response of P2X2aR (left) and P2X2bR (right) to 100-µM ATP stimulation for 70 s in the presence of NMDG⁺-only medium. (A) Current simulations initially exhibiting a brief and small outward current generated by P2X2aR- and P2X2bR-expressing model cells followed by an inward current. The current is outward because states Q₁, Q₂ have reversal potential (E₁₂) more negative than the holding potential V . P2X2aR currents desensitize much more slowly than P2X2bR, because the loss of dilated states is more prominent in the latter. The very fast accumulation of receptors in states Q₁ + Q₂ relative to the slow accumulation of receptors in the states Q₃ + Q₄ (B) is essential for reproducing the shift in the reversal potential in the I-V curves (C) during voltage ramps (−80 to +80 mV delivered twice per second to P2X2aR and twice per 100 ms to P2X2bR). The slopes of the I-V curves in C decrease because L₃ > L₄ (i.e., desensitization masks dilation).