Kinetic simulations using a linear gating scheme can broadly reproduce pH-dependent deactivation. (A) Kinetic scheme from Gründer and Pusch (25) used for simulations. (B) Simulated responses to a triple-jump protocol using a range of pHs from the scheme of Gründer and Pusch (25) as published (Left, black subheading), with fixed open and shut rates (Center Left, dark red subheading), with fixed open and shut rates plus stoichiometric binding (Center Right, purple subheading), or fit directly to data (Right, green subheading). (C) pH response curves for each of the models described above, as well as data obtained for rat ASIC1a (gray circles and gray fit line). Data are from four separate patches, and error bars show SEM. G & P, Gründer and Pusch. (D) Weighted deactivation time constants for each of the models tested, as well as data for rat ASIC1a (gray circles and line). To correct for shifts in apparent pH affinity in the models, the activation rheobase was determined (as in Fig. 2) and triple-jump simulations were performed using a pH range between that rheobase and 1 pH unit greater.