Changes in the pH_o sensitivity of TRPM2 mutants. (A–G) Dose–response curves of the effects of acidic pH_o on mutants H973Q, Q981E, D987Q, H995Q, D1002N, E1010Q/D1012N, and E1022Q. Current amplitudes at the indicated pHs were normalized to the maximal current amplitude at pH_o 7.4. Inset panels illustrate original recordings of WT TRPM2 and the mutants at pH 7.4 and 6.0. Best fit of the dose–response curves yielded IC₅₀s for the mutants indistinguishable from that of WT TRPM2. (H–J) Altered pH_o sensitivity in H958Q, D964N, and E994Q compared with WT TRPM2. Dose–response curves were rightward shifted, and the IC₅₀s were changed by ∼1 pH unit for H958Q, D964N, and E994Q, respectively. Inset panels illustrate representative recordings at pH 7.4 and 6.0. Note that the linear I-V relation of WT TRPM2 was not changed in H958Q, D964N, and E994Q. The Hill coefficient was n_H = 1.4 ± 0.1 for WT TRPM2, n_H = 1.0 ± 0.1 for H958Q, n_H = 1.7 ± 0.3 for D964N, and n_H = 3.2 ± 0.3 for E994Q.