NM potentiates and also activates TRPM7 channels in hippocampal neurons. A, left, trace examples of the TRPM7 currents. TRPM7 was evoked by 0.1 mM Ca2+ (and 0.1 mM Mg2+). Pre-expose: NM (200 μM) was applied before lowering divalent cations for 1-2 minutes; co-apply: NM (200 μM) was applied together with 0.1 mM Ca2+ (and 0.1 mM Mg2+). Right, bar graph showing the potentiated ratio by NM on the TRPM7. n = 7, ***, p < 0.01 vs. control. B, NM opens TRPM7 at the physiological concentration of divalent cations. Left, examples of TRPM7 current trace monitored by voltage ramps (-100 mV to 100 mV). Divalent cation concentration was 2 mM Ca2+ and 1 mM Mg2+. Right, I-V curve from voltage ramps. 200 μM NM caused marked while 25 μM NM have little effects on TRPM7, n = 6. C, NM activates and also blocks TRPM7 channel. Left, trace example of NM-induced current. Bath solution contained 2 mM Ca2+ and 1 mM Mg2+ and stayed unchanged. Black bar indicates application of NM and white bar indicates washout of NM. NM (200 μM) at the physiological concentration of cations directly induces an inward current, which became larger upon brief NM removal (inset enlarged). n = 5. Right, bar graph showing amplitude of NM-induced current (243 ± 66 pA) compared to current amplitude upon NM washout (379 ± 86 pA).