Figure 1.

pH_i regulates TMEM16F ion channel activity. (A) Representative TMEM16F currents recorded from inside-out patches perfused with intracellular solutions containing 100 µM Ca²⁺ at different pH_i values. Currents were evoked by voltage steps from −100 to +100 mV with 20 mV increments, and the holding potential was −60 mV. All traces shown were from the same patch. (B) Mean G-V relations of the TMEM16F channels under different pH_i values at 100 µM Ca²⁺. Relative conductance was determined by measuring the amplitude of tail currents 400 µs after repolarization to a fixed membrane potential (−60 mV). The smooth curves represent Boltzmann fits G/G_max = 1/{1 + exp[−ze(V − V_1/2]/kT}. G_max is tail current amplitude in response to depolarization to +100 mV in 100 µM Ca²⁺ at pH_i 8.9. Error bar represents SEM (n = 7). (C) G-pH_i relationship for TMEM16F channels. Data were normalized to pH_i 8.9. Dashed line represents Boltzmann fit. G-pH_i curves from 6.1 to 8.9 were fitted with linear regression shown as the solid lines, which aligned well with the Boltzmann fits (dashed line). Thus, the mean slopes from linear regression were used as a parameter for pH_i sensitivity in later experiments (n = 7).