Iodide inhibits human TRPM7 currents independently of intracellular Mg2+. Whole-cell patch clamp experiments were performed in tetHEKTRPM7 cells. Voltage ramps were from −100 to +100 mV over 50 ms and given at an interval of 2 s. TRPM7 current amplitudes were assessed at +80 mV, averaged and normalized to cell size (in pF). Error bars indicate SEM. For detailed solution composition see “Methods”. a TRPM7 currents measured in cells perfused with either 14 mM (solid circles) or 154 mM (open circles) intracellular Cl− solution in the absence of intracellular Mg2+ (n = 6–8). b TRPM7 currents in cells perfused with either 14 mM (solid circles) or 154 mM (open circles) intracellular bromide (Br−) solution in the absence of Mg2+ (n = 6–8). c TRPM7 currents in cells perfused with either 14 mM (solid circles) or 154 mM (open circles) intracellular iodide (l−) solution in the absence of Mg2+ (n = 6–8). d TRPM7 current development in the presence of 800 μM Mg2+ and either 14 mM (solid circles) or 154 mM (open circles) intracellular Cl− (n = 6–8). e TRPM7 currents in 14 or 154 mM intracellular Br− and 800 μM Mg2+ (n = 6–8). f TRPM7 currents in 14 or 154 mM intracellular I− and 800 μM Mg2+ (n = 6–8). g Representative I/V curve for TRPM7 with intracellular 14 mM (black trace) or 154 mM Br− (red trace) in the experiments described in panel e. h Representative I/V relationships for TRPM7 with 14 mM (black trace) or 154 mM (red trace) intracellular I− solution in the experiments described in panel c and panel f, respectively. All I/V curves were extracted at 200 s experimental time. i Dose–response curves for TRPM7 inhibition by increased I− concentrations in the absence (open circles) or presence (solid circles) of intracellular 800 μM Mg2+. Data points correspond to average current amplitudes measured at +80 mV at 200 s of whole cell recording, normalized to cell size and plotted as a function of internal I− concentration (n = 6–8). The best fit was obtained by a Hill coefficient close to −4 and −13 for the responses with intracellular 800 μM Mg2+ (solid circles) or without intracellular Mg2+ (open circles), respectively. Therefore the coefficients were fixed at those values, respectively. With intracellular Mg2+, the calculated IC50 value for I−-induced inhibition of TRPM7 currents is 59 ± 1 mM, and 120 ± 6 mM without Mg2+