FIGURE 5.

Structure-activity relationship of AMI derivatives. A, schematic demonstration for structure-activity relationship of AMI. B and C, representative current traces showing the channel activation under neutral pH (B) or inhibition of pH 5.0-activated currents (C) from ASIC3 expressing CHO cells induced by compounds as indicated. Every compound was used at the concentration of 1 mm. Different colored traces represent the currents induced in the presence of different compounds, in which black is for AMI; red is for methyl-3,5-diamino-6-chloropyrazine-2-carboxylate; and blue is for 5-(N-methyl-N-isobutyl)amiloride, respectively. The stimulatory and inhibitory results from 5-(N,N-dimethyl)- or 5-(N-methyl-N-isobutyl)amiloride (data not shown) were similar to that of 5-(N-ethyl-N-isopropyl) amiloride (blue). D, pooled data from experiments in C. The inhibition ratio was defined similarly as shown in Fig. 4B. Data points are means ± S.E. of four to seven measurements. **, p < 0.001 versus zero.