Formaldehyde increases intracellular calcium concentration in primary cultured hippocampal neurons partly through NMDA receptors and T-type calcium channels

Objective Formaldehyde at high concentrations is a contributor to air pollution.It is also an endogenous metabolic product in cells,and when beyond physiological concentrations,has pathological effects on neurons.Formaldehyde induces mis-folding and aggregation of neuronal tau protein,hippocampal neuronal apoptosis,cognitive impairment and loss of memory functions,as well as excitation of peripheral nociceptive neurons in cancer pain models.Intracellular calcium([Ca;];) is an important intracellular messenger,and plays a key role in many pathological processes.The present study aimed to investigate the effect of formaldehyde on[Ca;];and the possible involvement of N-methyl-Z)-aspartate receptors （NMDARs） and T-type Ca;channels on the cell membrane.Methods Using primary cultured hippocampal neurons as a model,changes of[Ca;];in the presence of formaldehyde at a low concentration were detected by confocal laser scanning microscopy.Results Formaldehyde at 1 mmol/L approximately doubled[Ca;];.（2R）-amino-5-phosphonopentanoate （AP5,25μmol/L,an NMDAR antagonist） and mibefradil(MIB,1 umol/L,a T-type Ca;channel blocker),given 5 min after formaldehyde perfusion,each partly inhibited the formaldehyde-induced increase of[Ca;];,and this inhibitory effect was reinforced by combined application of AP5 and MIB.When applied 3 min before formaldehyde perfusion,AP5 （even at 50μmol/L） did not inhibit the formaldehyde-induced increase of[Ca;];but MIB（1 umol/L） significantly inhibited this increase by 70%.Conclusion These results suggest that formaldehyde at a low concentration increases[Ca;];in cultured hippocampal neurons;NMDARs and T-type Ca;channels may be involved in this process.