It has been demonstrated that cancer tissues can secret endogenous formaldehyde.In the central nervous system, formaldehyde at pathological concentration can induce misfolding and aggregation of neuronal tau in hippocampus neurons, which is closely related to neurodegeneration.The present study aims to find the involved ion channels of formaldehyde effect on hippocampus neurons.Intracellular calcium is an important intracellular messenger, playing a key role in the whole cell cycle.Based on the changes of intracellular calcium signaling([Ca2+]i) by confocal images, we found that formaldehyde at a low concentration (1 mM) could increase [Ca2+]i in primary cultured hippocampal neurons by one fold.Both (2R)-amino-5-phosphonopentanoate (AP5, 25 μM, a selective NMDAR antagonist) and mibefradil (1 μM, a blocker of T-type calcium channels), given five minutes after formaldehyde perfusion, partially reverses the increased [Ca2+]i of hippocampus neurons, and this effect could be reinforced when they are given simultaneously.Three minutes before formaldehyde perfusion, AP5 (even at 50 μM) could not inhibit the formaldehyde-induced [Ca2+]i increase.But mibefradil (1 μM), given three minutes before formaldehyde, can significantly inhibit formaldehyde effect nearly by seventy-percentage.The results suggest that formaldehyde at a very low pathological concentration could increase intraeellular calcium concentration in hippocampal neurons; NMDA receptors and T-type calcium channels are the main potential targets of formaldehyde.