Modeling mechanosensitive responses of Hv1 proton channels via two-, four-, or six-state kinetic schemes. Simulations of time courses of normalized proton conductance (G/G_max(t)) in response to increase in membrane tension for dimeric (A–C) and monomeric Hv1 (D). The kinetic schemes used for the simulations are shown in Fig. S1. Parameter values are in Tables S1, S2, and S3. Note that dimer kinetics are ∼10 times slower than monomer kinetics. (A and B) Simulation of Hv1 WT at V_m near the foot of its G-V curve (“−20 mV”, see Fig. 6). B shows how the O (blue) and O_p (green) states contribute to the total conductance in the four-state model. Insets show the changes in state probabilities at the onset and offset of the pressure pulse. (C) Simulation of Hv1 dimer at V_m near the top of the G/V curve (“+80 mV”; see data traces in Fig. 3). Inset shows an enlarged view of the currents predicted by the three models during the pressure pulse. (D) Simulation of Hv1NC_VSP at V_m = 80 mV (see data traces in Fig. 4). Inset in the top panel shows an enlarged view of the currents predicted by the two- and four-state models during the pressure pulse. Instantaneous onset and offset of increased membrane tension (in response, experimentally, to applied pipette aspiration, i.e., “Pressure on”) is assumed. Asterisks in A and B indicate a step to V_hold simultaneous with Pressure off, as in some experiments.