(A) Local alignment of the β11–12 linker of resting (blue, PDB:5WKV) and open (green, PDB:4NTW) states. Leu414 and Asn415 side chains are depicted as ball and stick. (B) Representative responses from cASIC1 wild type (left) and L414A (right) to pH stimuli ranging from pH 7 to 5. (C) Summary of pH response curves for cASIC1 wild type (black) and L414A (red). (D) pH50 values of activation for all patches from panel (C). (E) Representative patch recording of L414A when activated by pH 6, 5, 4.4, 4.2 and 4 (left to right) but zoomed in on the sustained current. (F) Summary of fold increase in sustained current for L414A patches at a range of pH values. Note the sizeable increase around the previously reported pH50 for this mutation. All error bars are S.E.M. and the circles are individual patches.