Figure 1.
Figure 1. Nonpurified pyridine dinucleotides act as low affinity TRPM2 activators. (A–C) Macroscopic T5L-TRPM2 currents elicited in inside-out patches by cytosolic application of saturating (125 µM) Ca2+ (black bars) and either 32 µM ADPR (dark blue bars) or increasing concentrations of nonpurified NAD (A, green bars), NAAD (B, blue bars), or NAADP (C, purple bars). (D) Dose–response curves for fractional current activation by ADPR (dark blue; replotted from Tóth and Csanády, 2012), and nonpurified NAD (green), NAAD (blue), and NAADP (purple). Currents were normalized to those measured in 32 µM ADPR. Solid lines are fits to the Hill equation yielding K1/2 = 1.4 ± 0.1 µM, n = 1.8 ± 0.2, and Irel;∞ = 0.96 ± 0.03 for ADPR; K1/2 = 73 ± 3 µM, n = 1.4 ± 0.1, and Irel;∞ = 0.96 ± 0.01 for NAD; K1/2 = 109 ± 17 µM, n = 1.3 ± 0.2, and Irel;∞ = 0.96 ± 0.06 for NAAD; and K1/2 = 226 ± 19 µM, n = 1.8 ± 0.2, and Irel;∞ = 0.78 ± 0.04 for NAADP. Error bars represent mean ± SEM.

Nonpurified pyridine dinucleotides act as low affinity TRPM2 activators. (A–C) Macroscopic T5L-TRPM2 currents elicited in inside-out patches by cytosolic application of saturating (125 µM) Ca2+ (black bars) and either 32 µM ADPR (dark blue bars) or increasing concentrations of nonpurified NAD (A, green bars), NAAD (B, blue bars), or NAADP (C, purple bars). (D) Dose–response curves for fractional current activation by ADPR (dark blue; replotted from Tóth and Csanády, 2012), and nonpurified NAD (green), NAAD (blue), and NAADP (purple). Currents were normalized to those measured in 32 µM ADPR. Solid lines are fits to the Hill equation yielding K1/2 = 1.4 ± 0.1 µM, n = 1.8 ± 0.2, and Irel;∞ = 0.96 ± 0.03 for ADPR; K1/2 = 73 ± 3 µM, n = 1.4 ± 0.1, and Irel;∞ = 0.96 ± 0.01 for NAD; K1/2 = 109 ± 17 µM, n = 1.3 ± 0.2, and Irel;∞ = 0.96 ± 0.06 for NAAD; and K1/2 = 226 ± 19 µM, n = 1.8 ± 0.2, and Irel;∞ = 0.78 ± 0.04 for NAADP. Error bars represent mean ± SEM.

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