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Fig. 4 ZEBRAFISH CLC-1 ORTHOLOGUES SHOW DIFFERENT PH DEPENDENCE AND 9-AC INSENSITIVITY A, representative current traces of human ClC-1 and zebrafish orthologues at pH 5.4. B, pH dependence of the apparent open probability (App Po) of human ClC-1 (N = 8), clc-1a (N = 7) and clc-1b (N = 9). Data points indicate means ± SD. Both clc-1 orthologues show marked inversion of their App Po under acidic conditions. C, analysis of 9-AC sensitivity. Bars represent means ± SD of the relative current intensity (normalized to control conditions in the absence of 9AC) measured at +70 mV. Two-tailed unpaired Student's t test statistical analysis was performed comparing control (Ctrl) and 100 µm/1 mm 9-AC groups for each clc-1 variant. 100 µm 9-AC significantly affected human ClC-1 elicited activity (N = 8, P = 0,13E-14), while no significant effect was detected in clc-1a (N = 4, P = 0.13) nor clc-1b (N = 9, P = 0.16). 1 mm 9-AC dramatically altered human ClC-1 activity (N = 4, P = 0.12E-22), also affecting clc-1b (N = 4, P = 4.70E-08). Significance is shown as: **** P ≤ 0.0001, *** P ≤ 0.001.