Purified pyridine dinucleotides do not activate TRPM2 channels even at very high concentrations. (A–C) Macroscopic T5L-TRPM2 currents evoked by cytosolic application of saturating Ca²⁺ (black bars) and either 32 µM ADPR (dark blue bars) or high concentrations of untreated or NUDT9-treated (“purified”) NAD (A, green bars), NAAD (B, blue bars), or NAADP (C, purple bars). (D) Fractional current activation by indicated concentrations (mM) of NUDT9-treated (“+”) or nonpurified (“−”) NAD (green), NAAD (blue), and NAADP (purple). Currents were normalized to those measured in 32 µM ADPR. Error bars represent mean ± SEM.