Kinetic scheme providing an interpretation of the findings on the deactivation kinetics of the mutant R198Q. Following activation, K_V7.2 channels tend to become resilient to close as they remain activated. This shows a reduction in the rate of deactivation, making it slower. The activated mutant R198Q becomes more stable as the channels remain activated by depolarization (Fig. 6 D). This happened at any pH_EXT. However, at low pH_EXT deactivation was faster for any duration of the activating pulse than those observed at higher pH_EXT (e.g., Fig. 6 D, pH_EXT 6.0, blue circles, and pH_EXT 8.0, purple squares, respectively). (A and B) This strongly suggests that the conformation of the highly protonated open channels (A) is less stable than that of the channels that are less protonated (B). Thus, at low pH_EXT, the channels readily deactivate, while at higher pH_EXT, the channels deactivate slowly.