Mild Acidosis Potentiates AGM-Induced ASIC3 Channel Activation. (A) Representative traces showing currents induced by acid with graded pH as indicated in the absence (black) or presence (grey) of AGM (1 mM). (B, C) Pooled data as shown in (A) illustrating pH-dependent interaction between AGM- and acid-induced transient (B) or sustained (C) inward currents. Each point is the mean ± S.E.M. of four to five measurements and the solid (black) or dashed (grey) lines are fits to the Hill equation. *p < 0.05, represents the significant difference of current amplitude in the absence or presence of AGM (1 mM). The pH at half maximal activation (pH50) values are 6.74 ± 0.02 (n = 3.6 ± 0.4) and 6.81 ± 0.02 (n = 3.8 ± 0.6) in the absence or presence of AGM, respectively. (D-F) Synergistic interaction between AGM (1 mM) and mild acidosis (pH 7.0). 'I', 'II', and 'III' in (D) indicate co-, pre-, and pre + co-administrations of AGM (1 mM) and mild acid (pH 7.0) as also represented in (E), respectively. The synergistic interaction between AGM and mild acidosis (pH 7.0) is suggested by the two-way ANOVA analysis (p < 0.0001). (F) Concentration-dependence of AGM under mild acidosis (pH 7.0). AGM was co-applied as shown in protocol I of (D). Data points are means ± S.E.M. of four to five measurements normalized to pH 7.0-induced currents (control, dashed line). Expected value is the linear summation of normalized currents induced by pH 7.0 and AGM individually. **p < 0.001.