DAPI and HSB strongly modulate TRPM7 current in hippocampal neurons. A, i, DAPI (250 μM) completely and reversibly blocked TRPM7 current (evoked by 0.1 mM Ca2+ and 0.1 mM Mg2+) in cultured hippocampal neuron, n = 5. ii, left, representative current traces of TRPM7 current blocked with various concentrations of DAPI. DAPI was acutely applied and washed out as indicated by black bar. DAPI rapidly blocked TRPM7 current. iii, concentration response of DAPI blockade of TRPM7 current. IC50: 38 ± 8 μM; hill coefficient: 1.8; n = 5. B, DAPI activated TRPM7 at 2 mM Ca2+ and 1 mM Mg2+, voltage ramps (-100 mV to 100 mV). Right, I-V plot. 100 μM DAPI have strong effect while 25 μM was without effect, n = 5. C, and D, HSB has similar effect as NM on TRPM7. C, co-applied HSB (200 μM) blocks TRPM7 current. D, pre-exposed HSB (200 μM) potentiated TRPM7 current by 6.0 ± 1.0 fold, n = 6, p < 0.01; while co-applied HSB inhibited 90 ± 1% of TRPM7 current, n = 5.