Figure 1

NM reversibly inhibits TRPM7 currents in HEK293T cells. A i, example peak currents recorded at +100 (filled circle) and -100 mV (open circle) (V_h = 0 mV) in the presence of 0.1 mM Ca²⁺ and 0.1 mM Mg²⁺ before and during NM: 100 μM, 250 μM, 500 μM, and 1 mM (filled bars). ii, example I-V curve for NM-induced inhibition of TRPM7 (+100 mV; IC₅₀: 617 ± 40 μM; Hill coefficient: 1.4; n = 14 and at -100 mV; IC₅₀: 514 ± 39 μM; Hill coefficient: 1.3; n = 14. B. i, example peak currents recorded at +100 (filled circle) or -100 mV (open circle) (V_h = 0 mV) in divalent free solution before and during NM: 1 μM, 10 μM, 50 μM, 100 μM, and 200 μM (filled bars). ii, example I-V curves of currents before (at 1 in A) and during applications of NM (at 2, 3, 4, 5 and 6 in A). iii, dose-response curve of inhibition by NM at +100 mV; IC₅₀: 121 ± 2 μM; Hill coefficient: 1.2; n = 6 and at -100 mV; IC₅₀: 15 ± 2 μM; Hill coefficient: 1.3; n = 6. C, example peak currents recorded at +100 (filled circle) and -100 mV (open circle) (V_h = 0 mV) in the presence of 0.1 mM Ca²⁺ and 0.1 mM Mg²⁺ before (a, d, g), during (b, e, h) and after (c, f, i) 1 mM NM. D, example I-V curves for WT TRPM7, E1052A, and D1054A mutants. E, inhibition of the average current density of inward currents mediated by WT TRPM7 or its mutants, recorded at -100 mV. Each column represents the mean ± s.e.m. (n = 7-14), ***, P < 0.001 vs. WT.